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MVC COVID-19 vaccine
MVC-COV1901 is a vaccine candidate developed and commercialized by Medigen Vaccine Biologics Corporation. The vaccine candidate contains a perfusion form of the SARS-Cov2 recombinant spike protein. Medigen has combined forces with Dynavax, which offers an advanced adjuvant, CpG 1018 (also known as ISS-1018), for use with its vaccine. As of September 2020, the vaccine candidate is in Phase 1 clinical trials to assess its safety and immunogenicity (NCT04487210).
The MVC COVID-19 vaccine, designated MVC-COV1901 and also known as the Medigen COVID-19 vaccine, is a protein subunit COVID-19 vaccine developed by Medigen Vaccine Biologics Corporation [zh] in Taiwan, American company Dynavax Technologies and the U.S. National Institute of Health.
This vaccine is made by the recombinant S-2P spike protein adjuvanted with CpG 1018 supplied by Dynavax. Preliminary results from Phase I trials on 77 participants were published in June 2021, indicating what the authors described as “robust” immune system response elicited by the vaccine.
The study authors have assessed the humoral immune response by measuring quantities of binding IgG to S protein, and also the cellular immune response by measuring the quantities of IFN-γ and IL-4 secreting T cells.
Taiwan-based Medigen Vaccine Biologics Corporation (MVC) and Dynavax Technologies Corporation, in the US, have announced the rollout of its COVID-19 vaccine, MVC-COV1901. Approximately 600,000 people are anticipated to receive the Medigen vaccine this week.
Ryan Spencer, Chief Executive Officer of Dynavax commented, “We are pleased that Medigen’s vaccine is now available for the people of Taiwan. We are very excited for this first, of hopefully multiple, EUAs and approvals for COVID-19 vaccines that include CpG 1018 adjuvant. Considering the limitations of current vaccines and the global vaccine shortage, we believe adjuvanted vaccines can contribute significantly to current vaccination efforts.”
In July, MVC received Taiwan Emergency Use Authorization and approval for inclusion in Taiwan’s COVID-19 vaccine immunization program, MVC-COV1901.
MVC COVID-19 vaccine is indicated for adults over 20 years old and is administered in two doses 28 days apart for prevention of COVID-19.
The Advisory Committee recommended that MVC should submit safety monitoring report monthly during the declared EUA period and should submit a vaccine effectiveness report within one year after obtaining EUA approval.
(CNN)Taiwan’s President Tsai Ing-wen received her first shot of the island’s homegrown Covid-19 vaccine on Monday, a public show of support for the new drug which is central to plans for inoculation self sufficiency amid low immunization rates and struggles to obtain vaccines from overseas.Monday’s island-wide rollout of the Medigen Covid-19 vaccine, developed by Taipei-based Medigen Vaccine Biologics Corporation, comes after the drug was approved for emergency use last month by Taiwanese authorities for anyone above 20 years old, with at least 28 days between the two doses.The vaccine has yet to complete phase 3 clinical trials and no efficacy data is available. Paul Torkehagen, Medigen’s director of overseas business development, told CNN in May that the company designed a “very large” phase 2 clinical trial to ensure the vaccine’s safety and effectiveness, with 3,800 participants. Normally, a stage 2 clinical trial only involves several hundred people. Data from the trials showed that 99.8% of participants were able to form antibodies against Covid-19 after taking two doses of the vaccine, Medigen’s CEO Charles Chen said.
Taiwanese President Tsai Ing-wen, center, receives her first shot of the island’s first domestically developed coronavirus vaccine at the Taiwan University Hospital in Taipei, Taiwan on Monday, August 23.
Taiwan’s Centers for Disease Control said in a July 19 statement that the vaccine posed no serious health effects. Taiwan has ordered 5 million doses of the vaccine from Medigen and more than 700,000 people have already signed up to receive it, according to Reuters.In a Facebook post after receiving the vaccine at a hospital in Taipei, Tsai said she hadn’t suffered from any post-vaccination pain and thanked the health care workers who had administered the shot.”Taking the vaccine can protect yourself, your family, as well as medical staff,” Tsai wrote. “Let’s do our part in boosting Taiwan’s collective defense against the virus!”With its borders sealed to most travelers and strict measures enacted to contain local outbreaks, Taiwan has so far been largely successful in containing Covid-19, reporting fewer than 16,000 total confirmed infections and 828 deaths. But the island has struggled to vaccinate its more than 23 million population, partly due to difficulties obtaining doses from international suppliers.Taiwan’s government has only managed to import around 10 million Covid-19 vaccines, according to Reuters. In July it ordered another 36 million doses of the Moderna shot.Fewer than 5% of Taiwan’s population has received both doses of their Covid-19 vaccine, according to Reuters, as the island delays second dose vaccinations so more people can receive a first shot.On Monday, Taiwan reported four new Covid-19 cases, according to the Central Epidemic Command Center (CECC). Authorities announced on the weekend they would ease virus prevention measures to allow for larger gatherings and the opening of study centers and indoor amusement parks.But Health and Welfare Minister Chen Shih-chung said current Covid-19 restrictions — which include the closure of bars and nightclubs — would remain in place until at least September 6, with the possibility of an extension if the global outbreak continued to grow.Taiwan could become increasingly isolated if it keeps pursuing its “Covid zero” strategy, with both Australia and New Zealand hinting they might abandon the approach once vaccinations reach a certain level.In an opinion piece published on Sunday, Australian Prime Minister Scott Morrison said that while lockdowns to prevent Covid-19 transmission were “sadly necessary for now,” they may not be once vaccination rates increased to the targets of 70% and 80%.”This is what living with Covid is all about. The case numbers will likely rise when we soon begin to open up. That is inevitable,” he said.In neighboring New Zealand, which has also attempted to eliminate the virus within its borders, Covid-19 response minister Chris Hipkins told local media the highly-contagious Delta variant raised “some pretty big questions about what the long-term future of our plans are.”“At some point we will have to start to be more open in the future,” he said.
On 16 February 2020, Medigen Vaccine Biologics Corp. (MVC) signed a collaboration agreement with National Institutes of Health (NIH) for COVID-19 vaccine development. The partnership will allow MVC to obtain NIH’s COVID-19 vaccine and related biological materials to conduct animal studies in Taiwan.
On 23 July 2020, Medigen Vaccine Biologics (MVC) announced collaboration with Dynavax Technologies to develop COVID-19 vaccine. The COVID-19 candidate vaccine will have the combination of SARS-CoV2 spike protein created by MVC and Dynavax’s vaccine adjuvant CpG 1018, which was used in a previously FDA-approved adult hepatitis B vaccine.
On 13 October 2020, Medigen Vaccine Biologics received Taiwan’s government subsidies for the initiation of Phase 1 Clinical Trial in Taiwan starting early October. The Phase 1 Clinical Trial was held at National Taiwan University Hospital with 45 participants ranging the age of 20-50.
On 25 January 2021, Medigen Vaccine Biologics initiated Phase 2 Clinical Trial for its COVID-19 vaccine candidate MVC-COV1901 with the first participant being dosed. The Phase 2 Clinical Trial for the MVC COVID-19 vaccine was a randomized, double-blinded, and multi-center clinical trial, planned to enroll 3,700 participants of any age 20 above.
On 10 June 2021, Medigen Vaccine Biologics released its COVID-19 vaccine Phase 2 interim analysis results, which demonstrates good safety profile in participants. The Phase 2 Clinical Trial in the end included 3,800 participants with all participants receiving second dose by 28 April 2021. Medigen Vaccine Biologics announced that it will request Emergency Use Authorization (EUA) with the concluding of the Phase 2 Clinical Trial.
On 20 July 2021, Medigen Vaccine Biologics filed a Phase 3 Clinical Trial IND application with Paraguay’s regulatory authority, which was later approved. The Phase 3 Clinical Trial, however, was different from regular Phase 3 Clinical Trial, which uses immune-bridging trial to compare the performance of MVC COVID-19 vaccine with the Oxford-AstraZeneca COVID-19 vaccine. The decision was a controversial announcement as immune-bridging trials were not fully approved or widely accepted by health authorities. In addition, the accuracy of immune-bridging trials were also been questioned for years.
In July 2021, Medigen commenced phase II trials for adolescents aged 12-18.
|Full authorization Emergency authorization|
On July 19, 2021, MVC COVID-19 vaccine obtained Emergency Use Authorization (EUA) approval from the Taiwanese government after fulfilling EUA requirements set by Taiwanese authority. The EUA, however, was met with controversy due to the lack of efficacy data and Phase 3 Clinical Trial. On August 23, 2021, President Tsai Ing-Wen was among the first Taiwanese to receive a dose of the vaccine. 
- ^ “Dynavax and Medigen Announce Collaboration to Develop a Novel Adjuvanted COVID-19 Vaccine Candidate”. GlobeNewswire. 23 July 2020. Retrieved 7 June 2021.
- ^ 黃驛淵 (10 June 2021). “【獨家】【國產疫苗解盲1】高端實體疫苗針劑首曝光 「每天9萬劑」生產基地直擊” (in Chinese). Mirror Media.
- ^ Jump up to:a b “Medigen Vaccine Biologics COVID-19 Vaccine Adjuvanted with Dynavax’s CpG 1018 Announces First Participant Dosed in Phase 2 Clinical Trial in Taiwan”. http://www.medigenvac.com. Retrieved 7 August 2021.
- ^ Jump up to:a b Hsieh SM, Liu WD, Huang YS, Lin YJ, Hsieh EF, Lian WC, Chen C, Janssen R, Shih SR, Huang CG, Tai IC, Chang SC (25 June 2021). “Safety and immunogenicity of a Recombinant Stabilized Prefusion SARS-CoV-2 Spike Protein Vaccine (MVCCOV1901) Adjuvanted with CpG 1018 and Aluminum Hydroxide in healthy adults: A Phase 1, dose-escalation study”. EClinicalMedicine: 100989. doi:10.1016/j.eclinm.2021.100989. ISSN 2589-5370. PMC 8233066. PMID 34222848.
- ^ “MVC and NIH Collaborate to Develop COVID-19 Vaccine”. http://www.medigenvac.com. Retrieved 7 August 2021.
- ^ “Medigen Collaborates with Dynavax to Develop Novel Adjuvanted COVID-19 Vaccine Candidate”. http://www.medigenvac.com. Retrieved 7 August 2021.
- ^ “MVC Signed an License Agreement with NIH on COVID-19 Vaccine”. Medigen. 5 May 2020. Retrieved 27 July 2021.
- ^ “Medigen’s COVID-19 Vaccine Combined with Dynavax’s CpG 1018 Adjuvant Receives Taiwan Government Subsidy with First Participant Dosed in Early October”. http://www.medigenvac.com. Retrieved 7 August 2021.
- ^ “A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Adult (COVID-19)”. clinicaltrials.gov. United States National Library of Medicine. Retrieved 11 March 2021.
- ^ “A Study to Evaluate the Safety and Immunogenicity of MVC-COV1901 Against COVID-19”. clinicaltrials.gov. United States National Library of Medicine. Retrieved 11 March 2021.
- ^ “A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Elderly Adults”. clinicaltrials.gov. United States National Library of Medicine. 28 March 2021. Retrieved 3 April 2021.
- ^ “MVC Released COVID-19 Vaccine Phase 2 Interim Analysis Result”. http://www.medigenvac.com. Retrieved 7 August 2021.
- ^ “MVC Announces Paraguay Approval of IND Application for Phase 3 Clinical Trial”. http://www.medigenvac.com. Retrieved 7 August 2021.
- ^ “A Study to Evaluate MVC-COV1901 Vaccine Against COVID-19 in Adolescents”. clinicaltrials.gov. United States National Library of Medicine. 6 July 2021. Retrieved 6 July 2021.
- ^ “MVC COVID-19 Vaccine Obtains Taiwan EUA Approval”. http://www.medigenvac.com. Retrieved 7 August 2021.
- ^ Taiwan begins contested rollout of new Medigen domestic vaccine, Nikkei Asia, Erin Hale, August 23, 2021
|Vaccine type||Protein subunit|
|Legal status||Full and Emergency Authorizations: List of MVC COVID-19 vaccine authorizations|
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|COVID-19 (disease)SARS-CoV-2 (virus)CasesDeaths|
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////////Medigen vaccine, MVC COVID-19 vaccine, SARS-CoV-2, covid 19, corona virus, taiwan, approvals 2021, iss 1018, CpG 1018, MVC-COV1901
NEW DRUG APPROVALS
A SARS-CoV-2 vaccine comprising a conjugate of the spike protein RBD domain with tetanus toxoid (Finlay Vaccine Institute of Cuba)
Soberana 02, is a conjugate vaccine developed by Instituto Finlay de Vacunas.
517 Zimmer, Carl; Corum, Jonathan; Wee, Sui-Lee. “Coronavirus Vaccine Tracker”. The New York Times. Retrieved 30 June 2021.
518 Sesin, Carmen (14 May 2021). “Cuba begins mass Covid-19 vaccine inoculation before concluding trials”. NBC News. Retrieved 2 July 2021.
Soberana 02, technical name FINLAY-FR-2, is a COVID-19 vaccine produced by the Finlay Institute, a Cuban epidemiological research institute. It is a conjugate vaccine. This candidate followed a previous one called SOBERANA-01 (FINLAY-FR-1). Professor Ihosvany Castellanos Santos said that the antigen is safe because it contains parts instead of the whole live virus, and therefore it does not require extra refrigeration, like other candidates in the world. According to the WHO candidate landscape vaccine document, this vaccine requires two doses, the second one being administered 28 days after the first shot.
The spike protein subunit is produced in Chinese hamster ovary cell culture. In a pre-print article scientists from Cuba explain details of the vaccines technology and production.[non-primary source needed]
Production Deliveries Planned Production Potential Production
Deliveries (0)Effective production (implies deliveries) (1)
The Cuban government says it is planning to produce 100 million doses of its vaccine to respond to its own demand and that of other countries. Cuba has also suggested that, once it’s approved, it will offer the vaccine to tourists visiting the country.
The production of the first batch of about 100,000 doses will start in April. José Moya, representative of the World Health Organization and the Pan American Health Organization (PAHO) in Cuba, suggested that after the vaccine passes all clinical stages, it could be included as part of PAHO’s Revolving Fund.
The roll-out began with an “Interventional Trial” that consisted of inoculating 150,000 at-risk participants which seems to be defined as health-care workers. On April 11, 2021, the Ministry of Public Health of Cuba announced that 75,000 health-care workers were inoculated with their first dose of either of the two Cuba’s Phase III vaccines (the other being Abdala).
Vietnam, Iran, Venezuela, Argentina, Pakistan, India, the African Union, Jamaica and Suriname have expressed interest in purchasing the vaccine, although they are waiting on Phase 3 results.
Iran has signed an agreement to manufacture the vaccine and Argentina is negotiating one. Additionally, the Cuban government offered a “transfer of technology” to Ghana and will also supply “active materials” needed to make the vaccine.
While the price is currently unknown, the commercialization strategy of the vaccine will be a combination of the “impact on health” and the capability of Cuba’s system to financially support “the production of vaccines and drugs for the country”, per the director of the Finlay Institute, Vicente Vérez.
FINLAY-FR-2, which started being developed in October 2020, had 40 volunteers for its Phase I, according to the Cuban Public Registry of Clinical Trials, with an open, sequential and adaptive study to assess safety, reactogenicity and explore immunogenicity of the vaccine.
Phase IIa involved 100 Cubans, and phase IIb of the vaccine will have 900 volunteers between 19 and 80 years. Vicente Vérez, director general of the Finlay Vaccine Institute, said that the vaccine has shown to give an immune response after 14 days. The second phase has been supervised by Iranian officials from the Pasteur Institute.
Phase III commenced at the beginning of March as originally scheduled, and “ready to publish” results are expected by June. The trial volunteers are divided into three groups: some will receive two doses of the vaccine 28 days apart, another group will get two doses plus a third immune booster (Soberana Plus), and the third a placebo.
Although the trials involve thousands of adult volunteers recruited in Havana, Cuba’s public health officials have said that they will also need to conduct phase III trials abroad because the island doesn’t have an outbreak of sufficient scale to produce meaningful statistics on vaccine protection.
On March 13, 2021, the Cuban Biotechnology and Pharmaceutical Industries Business Group (BioCubaFarma) announced on social media that it had sent 100,000 doses of its Soberana 02 coronavirus vaccine candidate to the Pasteur Institute of Iran for clinical testing, “as part of the collaboration with other countries in the development of COVID-19 vaccines.” 
On April 26, 2021, it was reported that a Phase III conducted by the Pasteur Institute of Iran was approved to be started in Iran It was previously reported that the Institute will host Phase 3 but the pre-requisites were “technology transfer and joint production”.
Mexico plans to host a phase 3 trial.
The “Interventional Study” is set both in Havana, Cuba’s capital and Santiago de Cuba, Cuba’s second most populous city  and in other provinces. On May 6, 2021, the Finlay Institute of Vaccines announced on social media that the following adverse events have been observed: injection site pain (20%), inflammation at the injection site (5%), and general discomfort (5%).
Full authorization Emergency authorization
- ^ “Cuba’s Soberana Plus against Covid-19 is showing good results”. Prensa Latina. Retrieved 10 May 2021.
- ^ Jump up to:a b c Malik JA, Mulla AH, Farooqi T, Pottoo FH, Anwar S, Rengasamy KR (January 2021). “Targets and strategies for vaccine development against SARS-CoV-2”. Biomedicine & Pharmacotherapy. 137: 111254. doi:10.1016/j.biopha.2021.111254. PMC 7843096. PMID 33550049.
- ^ Santos IC (January 2021). “Rapid response to: Covid 19: Hope is being eclipsed by deep frustration”. BMJ. 372: n171. doi:10.1136/bmj.n171.
- ^ “Draft landscape and tracker of COVID-19 candidate vaccines”. http://www.who.int. World Health Organization. Retrieved 2021-02-04.
- ^ Jump up to:a b c d Rasmussen SE, Eqbali A (12 January 2021). “Iran, Cuba, Under U.S. Sanctions, Team Up for Covid-19 Vaccine Trials”. The Wall Street Journal.
- ^ “Cuba’s homegrown Covid vaccine shows promise”. http://www.ft.com. Retrieved 2021-06-20.
- ^ “Cuba encouraged by early efficacy results of homegrown COVID-19 vaccine”. http://www.zawya.com. Retrieved 2021-06-20.
- ^ Acosta, Nelson (2021-06-20). “Cuba encouraged by early results of homegrown COVID-19 vaccine amid worst outbreak”. The Age. Retrieved 2021-06-20.
- ^ Valdes-Balbin, Yury; Santana-Mederos, Darielys; Quintero, Lauren; Fernández, Sonsire; Rodriguez, Laura; Ramirez, Belinda Sanchez; Perez, Rocmira; Acosta, Claudia; Méndez, Yanira; Ricardo, Manuel G.; Hernandez, Tays (2021-02-09). “SARS-CoV-2 RBD-Tetanus toxoid conjugate vaccine induces a strong neutralizing immunity in preclinical studies”. doi:10.1101/2021.02.08.430146.
- ^ Melimopoulos, Elizabeth. “Is Cuba closing in on COVID vaccine sovereignty?”. http://www.aljazeera.com. Retrieved 2021-05-07.
- ^ “Optimism as Cuba set to test its own Covid vaccine”. BBC News. 2021-02-16. Retrieved 2021-05-07.
- ^ “Cuba espera fabricar 100 millones de dosis de su candidato vacunal Soberana 02”. Nodal (in Spanish). 21 January 2021.
- ^ “Vaccino, Cuba pronta a produrre 100 milioni di dosi di ‘Soberana 02′”. Dire (in Italian). 21 January 2021.
- ^ Jump up to:a b Ribeiro G (4 February 2021). “Cuba to offer coronavirus vaccines to tourists”. Brazilian Report.
- ^ Jump up to:a b “Coronavirus: Vacuna cubana Soberana 02 alista fase 3 y ensayos”. Deutsche Welle (in Spanish). 5 February 2021.
- ^ Meredith S (23 February 2021). “‘Sun, sea, sand and Soberana 02’: Cuba open to inoculating tourists with homegrown Covid vaccine”. CNBC.
- ^ “Coronavirus: Vacuna cubana Soberana 02 alista fase 3 y ensayos”. Deutsche Welle (in Spanish). 5 February 2021.
Las expectativas sobre Soberana 02 son tales que el titular del organismo estatal que desarrolló la vacuna, Vicente Vérez, confirmó que mientras se aguarden los resultados de la Fase 3 solo en La Habana, en abril se dará inicio a la producción del primer lote, de alrededor de 100 mil dosis.
- ^ “Cuba anuncia fase 3 de la vacuna Soberana 02”. La Jornada(in Spanish). 7 February 2021.
Una vez que superen las etapas clínicas, la OMS podría contar con el fármaco cubano, afirmó Moya, y “pasar a ser parte del grupo de vacunas que se oferten a través del Fondo Rotatorio”, un mecanismo que desde hace cuatro décadas permite gestionar antígenos e insumos a los países de las Américas.
- ^ “SOBERANA – INTERVENTION | Registro Público Cubano de Ensayos Clínicos”. rpcec.sld.cu. Retrieved 2021-04-11.
- ^ “Cuba says it’s ‘betting it safe’ with its own Covid vaccine”. NBC News. Retrieved 2021-04-11.
- ^ “Cuba begins testing 2nd COVID-19 vaccine on health care workers”. medicalxpress.com. Retrieved 2021-04-11.
- ^ Ministry of Public Health of Cuba (11 April 2021). “[Translated] “The administration of the 1st dose of the Cuban vaccine candidates #Soberana02 and #Abdala to the 75 thousand health workers and Biocubafarma who are part of the intervention study taking place in #LaHabana has concluded.””. Twitter. Retrieved 2021-04-11.
- ^ “Cuban scientists, health workers received first anti-Covid-19 dose”. http://www.plenglish.com/index.php?o=rn&id=66247&SEO=cuban-scientists-health-workers-received-first-anti-covid-19-dose (in Spanish). Retrieved 2021-04-11.
- ^ Jump up to:a b “ILARREGUI (EMBAJADOR EN CUBA): “DURANTE ESTE AÑO PODREMOS TENER VACUNAS CUBANAS EN ARGENTINA””. RadioCut. Retrieved 2021-05-07.
- ^ Jump up to:a b Argentina, Cadena 3. “Argentina comenzó a negociar con Cuba la vacuna Soberana”. Cadena 3 Argentina (in Spanish). Retrieved 2021-05-07.
- ^ Jump up to:a b de 2021, 6 de Mayo. “Sin definiciones sobre cuándo podrían llegar, el Gobierno avanza para conseguir las vacunas Soberana y Abdala de Cuba”. infobae (in Spanish). Retrieved 2021-05-07.
- ^ admin (2021-04-09). “Cuba’s COVID-19 Vaccines Being Sought After by CARICOM Countries”. Caribbean News. Retrieved 2021-05-07.
- ^ Guenot, Marianne (2021-02-15). “Cuba is working on a homegrown COVID-19 vaccine program. It has a history of fighting disease without help from the West”. Business Insider France (in French). Retrieved 2021-05-07.
- ^ Página12 (2021-01-22). “Soberana 02: Cuba prepara cien millones de dosis de la vacuna contra el coronavirus | “No somos una multinacional. Nuestro fin es crear salud”, dijo el director del Instituto Finlay de Vacunas”. PAGINA12. Retrieved 2021-05-07.
- ^ “Cuban coronavirus vaccine to start third clinical trial phase in Iran”. Tehran Times. 2021-04-18. Retrieved 2021-05-07.
- ^ Banini | 0542440286, Awofisoye Richard. “CEO OF FDA DISCUSSES PRODUCTION OF COVID-19 VACCINE WITH CUBAN AMBASSADOR”. http://www.fdaghana.gov.gh. Retrieved 2021-05-05.
- ^ “Cuba To Transfer COVID-19 Vaccine Technology To Ghana”. http://www.gnbcc.net. Retrieved 2021-05-05.
- ^ “Cuban government offers to transfer COVID-19 Soberana 02 vaccine technology to Ghana”. Rio Times Online. 16 February 2021.
- ^ “Coronavirus: Cuba will produce 100 million doses of its Soberana 02 vaccine”. OnCubaNews English. 2021-01-21. Retrieved 2021-05-07.
- ^ “SOBERANA 02 | Registro Público Cubano de Ensayos Clínicos”. Cuban Registry of Clinical Trials (in Spanish). Retrieved 24 January 2021.
- ^ Cuba inicia nova fase de testes com vacina que desenvolve contra covid-19 (in Portuguese), Universo Online, 19 January 2021, Wikidata Q105047566
- ^ “Cuba apuesta por crear primera vacuna de América Latina contra el covid-19”. France 24 (in Spanish). 2021-01-21. Retrieved 24 January 2021.
- ^ “Cuba negotiates with other countries to develop phase 3 of Soberana 02 vaccine”. OnCubaNews English. 2020-12-30. Retrieved 24 January 2021.
- ^ Jump up to:a b “Cuban-developed vaccine enters Phase III trial”. ABS CBN. 5 March 2021.
- ^ Mega, Emiliano Rodríguez (2021-04-29). “Can Cuba beat COVID with its homegrown vaccines?”. Nature. doi:10.1038/d41586-021-01126-4. PMID 33927405.
- ^ “Cuban Vaccine Ready in July. Interview with the Cuban Ambassador to the Czech Republic”. Pressenza. 2021-03-23. Retrieved 2021-04-29.
- ^ Augustin, Ed (2021-05-12). “Cuba deploys unproven homegrown vaccines, hoping to slow an exploding virus outbreak”. The New York Times. ISSN 0362-4331. Retrieved 2021-05-14.
- ^ “L’esempio cubano sui vaccini”. http://www.ilfoglio.it (in Italian). Retrieved 2021-05-07.
- ^ Avances de las vacunas cubanas contra la COVID-19, retrieved 2021-05-07
- ^ Mega, Emiliano Rodríguez (2021-04-29). “Can Cuba beat COVID with its homegrown vaccines?”. Nature. doi:10.1038/d41586-021-01126-4. PMID 33927405.
- ^ Yaffe, Helen. “Cuba’s five COVID-19 vaccines: the full story on Soberana 01/02/Plus, Abdala, and Mambisa”. LSE Latin America and Caribbean blog. Retrieved 2021-03-31.
- ^ “Cuba sends 100,000 doses of the Soberana 02 vaccine candidate to Iran” oncubanews.com. Retrieved 19 March 2021.
- ^ “Iran-Cuba vaccine enters phase three clinical trials”. Tehran Times. 2021-04-26. Retrieved 2021-04-28.
- ^ “Cuban coronavirus vaccine to start third clinical trial phase in Iran”. Tehran Times. 2021-04-18. Retrieved 2021-04-28.
- ^ “América Latina apura una vacuna propia. Cuba, adelante; México avanza. Pero no son los únicos”. http://www.poresto.net (in Spanish). Retrieved 2021-04-28.
- ^ Marsh S (2021-01-09). “Cuba to collaborate with Iran on coronavirus vaccine”. Reuters. Retrieved 2021-01-24.
- ^ “Mexico Hopes to Work With Cuba on Covid Vaccine Phase 3 Trial”. Bloomberg.com. 2021-02-14. Retrieved 2021-05-07.
- ^ Marsh, Sarah (2021-03-24). “Nearly all Havana to receive experimental Cuban COVID-19 vaccines”. Reuters. Retrieved 2021-04-28.
- ^ BioCubaFarma (April 6, 2021). “[Translated] Updating the vaccination process with vaccine candidates #Soberana02 and #Abdala during ongoing clinical trials.#VacunasCubanasCovid19”. Twitter (in Spanish). Retrieved 2021-04-11.
- ^ “Intervention study with Covid-19 vaccine candidate Abdala begins”. Radio Cadena Agramonte. Retrieved 2021-04-28.
- ^ “Cuba administers over 62,000 doses in intervention trials”. http://www.plenglish.com/index.php?o=rn&id=66012&SEO=cuba-administers-over-62000-doses-in-intervention-trials (in Spanish). Retrieved 2021-04-28.
- ^ “[Trnslated] In more than 62 thousand applied doses of #Soberana02 the safety of the vaccine has been demonstrated. Adverse effects have been: 👉 Pain at the injection site (20%). 👉 Redness at the injection site (5%). 👉 Feeling of general malaise (5%)”. Twitter. Retrieved 2021-05-07.
- ^ “[Translated]In more than 62 thousand applied doses of #Soberana02 the safety of the vaccine has been demonstrated. Adverse effects have been: 👉 Pain at the injection site (20%). 👉 Redness at the injection site (5%). 👉 Feeling of general malaise (5%)”. Facebook. Retrieved 2021-05-07.
|Other names||FINLAY-FR-2, SOBERANA PLUS|
|Legal status||Full and Emergency Authorizations: List of Soberana 02 authorizations|
|Part of a series on the|
|COVID-19 (disease)SARS-CoV-2 (virus)CasesDeaths|
|showEconomic impact and recession|
/////////////////SARS-CoV-2, covid 19, corona virus, vaccine, iran, cuba, Soberana 02, FINLAY-FR-2
Nature (London, United Kingdom) (2021),
NEW DRUG APPROVALS
An optimized, non-chemical modified mRNA encoding the prefusion-stabilized full-length spike protein of SARS-CoV-2 virus (Curevac)
zorecimeran, CureVac COVID-19 vaccine
NCT04674189 NCT04449276 NCT04515147 NCT04652102
|CVnCoV||Humoral and cellular responses||CD4+ T-cells, CD8+ T-cells||N/A||N/A||Rhesus macaque|||
124. Rauch S, Gooch K, Hall Y, Salguero FJ, Dennis MJ, Gleeson FV. et al. mRNA vaccine CVnCoV protects non-human primates from SARS-CoV-2 challenge infection. bioRxiv. 2020. 2020 12.23.424138
The CureVac COVID-19 vaccine is a COVID-19 vaccine candidate developed by CureVac N.V. and the Coalition for Epidemic Preparedness Innovations (CEPI). The vaccine showed inadequate results in its Phase III trials with only 47% efficacy. The European Medicines Agency stated that: “(…) medicine developers should design studies to demonstrate a rate of efficacy of at least 50%.”.
The CVnCov Vaccine (or CV07050101) is in development by CureVac AG. The vaccine uses mRNA technology to create a protein associated with SARS-CoV2, and upon administration and replication, to initiate subsequent immune responses in the body. As of June 2020, the company received regulatory approval from German and Belgian Authorities to commence Phase 1 clinical trials of this vaccine (NCT04449276).
On 16 June 2021, CureVac said its vaccine showed 47% efficacy from its Phase III trial. This was based on interim analysis of 134 COVID cases in its Phase III study conducted in Europe and Latin America. The final analysis for the trials requires a minimum of 80 additional cases.
CVnCoV is an mRNA vaccine that encodes the full-length, pre-fusion stabilized coronavirus spike protein, and activates the immune system against it. CVnCoV technology does not interact with the human genome. CVnCoV uses unmodified RNA, unlike the Pfizer–BioNTech COVID-19 vaccine and Moderna COVID-19 vaccine, which both use nucleoside-modified RNA.
Manufacturing of mRNA vaccines can be performed rapidly in high volume, including use of portable, automated printers (“RNA microfactories”) for which CureVac has a joint development partnership with Tesla.
mRNA vaccines require stringent cold chain refrigeration throughout manufacturing, distribution and storage. The CureVac technology for CVnCoV uses a non-modified, more natural mRNA less affected by hydrolysis, enabling storage at 5 °C (41 °F) and relatively simplified cold chain requirements that facilitate up to three months of storage and distribution to world regions that do not have specialized ultracold equipment.
CureVac has a European-based network to accelerate manufacturing of CVnCoV, if proven safe and effective, for production of up to 300 million doses in 2021 and 600 million doses in 2022. An estimated 405 million doses will be provided to EU states.
In December 2020, CureVac began a Phase III clinical trial of CVnCoV with 36,500 participants. Bayer will provide clinical trial support and international logistics for the Phase III trial, and may be involved in eventual manufacturing should the vaccine prove to be safe and effective. In February 2021, the EU’s CHMP started a rolling review of CVnCoV. In April 2021, the same procedure began in Switzerland.
- ^ “CureVac focuses on the development of mRNA-based coronavirus vaccine to protect people worldwide”. CureVac(Press release). 15 March 2020. Retrieved 17 February 2021.
- ^ Jump up to:a b Burger, Ludwig (16 June 2021). “CureVac fails in pivotal COVID-19 vaccine trial with 47% efficacy”. Reuters. Retrieved 17 June 2021.
- ^ https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/vaccines-covid-19/covid-19-vaccines-studies-approval#what-is-the-level-of-efficacy-that-can-be-accepted-for-approval?-section
- ^ “CureVac Provides Update on Phase 2b/3 Trial of First-Generation COVID-19 Vaccine Candidate, CVnCoV”. 16 June 2021.
- ^ https://www.curevac.com/wp-content/uploads/2020/10/20201023-CureVac-Manuscript-draft-preclinical-data.pdf
- ^ Jump up to:a b c Schlake T, Thess A, Fotin-Mleczek M, Kallen KJ (November 2012). “Developing mRNA-vaccine technologies”. RNA Biology. 9(11): 1319–30. doi:10.4161/rna.22269. PMC 3597572. PMID 23064118.
- ^ “Understanding mRNA COVID-19 vaccines”. US Centers for Disease Control and Prevention. 18 December 2020. Retrieved 5 January 2021.
- ^ “COVID-19”. CureVac. Retrieved 21 December 2020.
- ^ Dolgin, Elie (25 November 2020). “COVID-19 vaccines poised for launch, but impact on pandemic unclear”. Nature Biotechnology: d41587–020–00022-y. doi:10.1038/d41587-020-00022-y. PMID 33239758. S2CID 227176634.
- ^ Jump up to:a b c Nawrat A (3 December 2020). “Q&A with CureVac: resolving the ultra-cold chain logistics of Covid-19 mRNA vaccines”. Pharmaceutical Technology. Retrieved 5 January 2021.
- ^ “Tesla to make molecule printers for German COVID-19 vaccine developer CureVac”. Reuters. 2 July 2020. Retrieved 19 December 2020.
- ^ Kartoglu U, Milstien J (July 2014). “Tools and approaches to ensure quality of vaccines throughout the cold chain”. Expert Review of Vaccines. 13 (7): 843–54. doi:10.1586/14760584.2014.923761. PMC 4743593. PMID 24865112.
- ^ Hanson CM, George AM, Sawadogo A, Schreiber B (April 2017). “Is freezing in the vaccine cold chain an ongoing issue? A literature review”. Vaccine. 35 (17): 2127–2133. doi:10.1016/j.vaccine.2016.09.070. PMID 28364920.
- ^ Jump up to:a b Kansteiner F (17 November 2020). “CureVac, armed with COVID-19 vaccine deal, plots ‘pandemic-scale’ Euro manufacturing expansion”. FiercePharma, Questex LLC. Retrieved 5 January2021.
- ^ “CureVac’s Covid-19 vaccine induces immune response in study”. Clinical Trials Arena. 3 November 2020. Retrieved 5 January 2021.
- ^ “CureVac’s COVID-19 vaccine triggers immune response in Phase I trial”. Reuters. 2 November 2020. Retrieved 5 January2021.
- ^ “Multicenter Clinical Study Evaluating the Efficacy and Safety of Investigational SARS-CoV-2 mRNA Vaccine CVnCoV in Adults 18 Years of Age and Older”. EU Clinical Trials Register. 19 November 2020. Retrieved 5 January 2021.
Proposed INN: zorecimeran
- ^ “A Study to Determine the Safety and Efficacy of SARS-CoV-2 mRNA Vaccine CVnCoV in Adults”. ClinicalTrials.gov. 8 December 2020. NCT04652102. Retrieved 19 December 2020.
- ^ Burger L (7 January 2021). “CureVac strikes COVID-19 vaccine alliance with Bayer”. Reuters. Retrieved 17 February 2021.
- ^ “CureVac and Bayer join forces on COVID-19 vaccine candidate CVnCoV”. CureVac (Press release). 7 January 2021. Retrieved 17 February 2021.
- ^ “EMA starts rolling review of CureVac’s COVID-19 vaccine (CVnCoV)”. European Medicines Agency (EMA) (Press release). 11 February 2021. Retrieved 12 February 2021.
- ^ “CureVac Initiates Rolling Submission With European Medicines Agency for COVID-19 Vaccine Candidate, CVnCoV”. CureVac(Press release).
- ^ “CureVac starts review process in Switzerland for COVID-19 vaccine hopeful”. Reuters. 19 April 2021. Retrieved 19 April 2021.
- ^ “Celonic and CureVac Announce Agreement to Manufacture over 100 Million Doses of CureVac’s COVID-19 Vaccine Candidate, CVnCoV”. CureVac (Press release). 30 March 2021. Retrieved 14 April 2021.
- ^ World Health Organization (October 2020). “International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 124 – COVID-19 (special edition)” (PDF). WHO Drug Information. 34 (3): 668–69. Archived (PDF) from the original on 27 November 2020.
- “Zorecimeran”. Drug Information Portal. U.S. National Library of Medicine.
|Other names||CVnCoV, CV07050101|
|Part of a series on the|
|COVID-19 (disease)SARS-CoV-2 (virus)|
- Rego GNA, Nucci MP, Alves AH, Oliveira FA, Marti LC, Nucci LP, Mamani JB, Gamarra LF: Current Clinical Trials Protocols and the Global Effort for Immunization against SARS-CoV-2. Vaccines (Basel). 2020 Aug 25;8(3). pii: vaccines8030474. doi: 10.3390/vaccines8030474. [Article]
- Speiser DE, Bachmann MF: COVID-19: Mechanisms of Vaccination and Immunity. Vaccines (Basel). 2020 Jul 22;8(3). pii: vaccines8030404. doi: 10.3390/vaccines8030404. [Article]
- CureVac & Covid-19 [Link]
- Smart Patients [Link]
- Regulatory News [Link]
NEW DRUG APPROVALS
Vaxine Pty Ltd company logo
Vaxine’s promising new COVID-19 vaccine candidate
A new multivalent COVID-19 vaccine developed by Australian company Vaxine to tackle the new virus variants could be game-changer in the fight against COVID-19
The world desperately needs a vaccine that blocks virus transmission and protects against all the variants. Covax-19 vaccine may soon change history”— Sharen Pringle, Vaxine Business Mananager
ADELAIDE, SA, AUSTRALIA, May 16, 2021 /EINPresswire.com/ — Professor Petrovsky, who is the Chairman and Research Director of Australian-based Vaxine Pty Ltd, explains that the two biggest challenges to tackling the COVID-19 pandemic are to develop a vaccine that completely prevents virus transmission something other COVID-19 have not been completely successful in achieving, and the second being to find a vaccine that protects equally against all the evolving immune-escape variants.
Professor Petrovsky has been researching coronavirus vaccines for the last 17 years, having previously published scientific papers on vaccines against both the SARS and MERS coronaviruses, which were highly protective in relevant animal models. He also recently published data from a collaboration with the US Army on development of a promising Ebola vaccine that protected mice against this most lethal disease after just a single vaccine dose. He has now successfully taken the same approach to design a protein-based vaccine against COVID-19.
Studies in a broad range of animal models including mice, hamsters, ferrets and monkeys, have recently revealed the high potential of this vaccine that is currently known as Covax-19(TM), but which likely will be soon rebranded as in its latest iteration it moves into late stage human trials in a number of countries.
Recent breakthrough data generated by Vaxine’s partner, Professor Kaissar Tabynov who leads the International Center for Vaccinology at the Kazakh National Agrarian University has shown that Vaxine’s unique spike protein antigen which is produced using insect cells in culture, was unique in that it not only totally protected hamsters from infection themselves but also prevented them from transmitting the virus to unvaccinated animals that were placed in the same cage two days after the vaccinated animals had been challenged with virus. Protection against transmission was not seen in hamsters given other vaccines making this finding unique to Vaxine’s spike protein antigen.
This hamster data reinforced findings in hamster, ferret and monkey challenge study performed by collaborating US Universities, who showed that two doses of Vaxine’s Covax-19 vaccine provided complete clearance of recoverable virus from the lungs and nose of animals when sampled just days after an infectious challenge.
“COVAX-19 vaccine has now been shown to be highly protective against the original Wuhan strain of the virus in hamster, ferret and monkey infection models performed by independent academic institutions in multiple countries, attesting to the strength of our protein-based vaccine approach”, says Prof. Petrovsky.
“A key element in the success of Covax-19 vaccine is the inclusion of Vaxine’s Advax adjuvant technology which acts as a turbocharger to drive an optimal immune response against the virus” explains Prof. Petrovsky who has been working on this promising vaccine adjuvant technology for the last 20 years with funding support from the US National Institutes of Health.
“We have now shown that our COVAX-19 vaccine can provide effective immunity including an ability to block nasal virus replication and this in turn successfully prevents transmission of the virus to vaccine-naïve animals,” he explains.
Follow on studies to confirm and expand upon these initial findings are currently underway at several US universities as well as Kazakh National Agrarian University, with a manuscript describing some of the initial animal data currently under review at a leading vaccine journal.
In another major breakthrough the team has now developed the vaccine into a multivariant format designed to protect against all the recently described variant strains of COVID-19, with work also underway on the most recently described Indian strains.
While the data is still preliminary says Prof. Petrovsky, the immune responses to the multivalent vaccine in mice are generating equally strong antibody binding activity against all the major virus variants. “This is extremely exciting as the world desperately needs vaccines able to protect against all the new strains of the virus including the UK, South African and Brazilian strains. By contrast , the currently available vaccines are clearly not as strong against some of these variants as they are against the original Wuhan strain” he explains.
Already there have been multiple confirmed cases of vaccine breakthrough where otherwise healthy individuals who have received mRNA, adenovirus or inactivated whole virus vaccines have become infected generally with either the South African or Brazilian variants.
This problem of immune-escape will only get worse over time as more complex variants emerge which is why Vaxine has been putting all its energy into finding a robust solution to this issue before proceeding with Phase 3 clinical trials of its Covax-19 vaccine.
Dr. Petrovsky went on to conclude “Now we have a multivalent formulation of Covax-19 vaccine that is showing high promise in animal studies, we plan to work as fast as we can to advance this new vaccine formulation in human trials, while expanding manufacturing capacity to ensure we are able to produce enough vaccine to meet the enormous global demand that will be attracted by such a successful vaccine.”
“To help us in this task Vaxine is looking to assemble a global network of partner organisations in countries around the world to assist Vaxine with vaccine development, clinical trials, manufacturing, distribution and sales. This is going to be a mammoth effort as we go to war against this insidious virus that continues to wreak havoc around the globe, with WHO recently predicting that the second year of the pandemic is likely to be much worse even than the first, an ominous warning for many countries that still remain poorly prepared and lacking in local vaccine manufacturing capability.
Vaxine wishes to help developing countries to establish their own local state-of-the-art vaccine manufacturing facilities, providing advice on appropriate facility design and undertaking technology transfer of its state of the art protein production technology to such facilities.
Countries in the developing world can no longer afford to sit and wait for outside organisations like COVAX to solve their vaccine supply problems, instead Vaxine proposes to help such countries find their own local solutions to the vaccine supply bottleneck for this.
Vaxine Pty Ltd
437 033 400
email us here……..https://www.einnews.com/pr_news/541113168/covid-19-vaccine-breakthrough
Currently, the Australian influenza vaccine and adjuvant specialist and the Polish protein drug maker have just inked a memorandum of understanding, so the terms of a future contract remain to be defined. However, the technology behind is interesting.
The partners intent to utilize an insect cell-based recombinant spike protein of SARS-CoV–2 in combination with Vaxine’s proprietary Advax™ adjuvant and have already started Phase I testing in Australia with first result expected later this month. The company announced it will use artificial intelligence to evalutate clinical data in real time and announced the ambition to complete Phase II and III trials at the end of this year. “Supported by Microsoft technology, we aim to collect and analyse the COVAX-19™ trial data in real time, rather than waiting until the end of the trial before seeing if the vaccine is working, which is the traditional process,” said Vaxine’s Research Director Professor Nikolai Petrovsky from Flinders University in Adelaide.
Preclinically, Vaxine Pty Ltd’s syntetic spike protein with the company’s non-inflammatory Advax™ adjuvant, induced antibody and T-cell immune responses against the co-administered antigen. In various animal models, Covax-19 vaccination provided robust protection against an infection with the novel coronavirus.
The Phase I of Vaxine Pty Ltd in running since July in 40 healthy volunteers. If results are positive, the Australian vaccine maker is to expand studies and manufacturing to Europe. Under a future agreement Mabion SA would lead clinical development, manufacturing, regulatory negotiations and could exclusively market the vaccine in the EU and – optionally – in the US……..https://european-biotechnology.com/up-to-date/latest-news/news/mabion-to-licence-covid-19-jab-from-vaxine-pty-ltd.html
////////////////COVAX-19, corona virus, covid 19, Vaxine, australia, vaccine
NEW DRUG APPROVALS
Recombinant vesicular stomatitis virus (rVSV) vaccine
Israel Institute for Biological Research
Hadassah Medical Center; Sheba Medical Center Hospital
The SARS-CoV-2 virus is responsible for the COVID-19 pandemic. The pandemic emerged from Wuhan Province in China in December 2019 and was declared by the WHO Director-General a Public Health Emergency of International Concern on 30 January 2020.
In this study, a vaccine developed by IIBR for SARS-CoV-2 virus will be assessed for its safety and potential efficacy in volunteers. The study is comprised of two phases, a dose-escalation phase (phase I) during which subjects (18-55 years old) will be randomly allocated to receive a single administration of IIBR-100 100 at low, mid or high dose or saline or two administrations of IIBR-100 at low dose, or saline, 28 days apart.
Based on results obtained during phase I, and cumulative phase I data review, the expansion phase (phase II) has begun, during which larger cohorts as well as elderly age subjects will be randomly allocated to receive a single administration of IIBR-100 at low, mid or high dose or saline, or two administrations of IIBR-100 at low, mid or high dose (prime-boost) or saline, 28 days apart. Additional top-dose (prime-boost) may be implemented when immunogenicity of any prime-boost arm is considered insufficient.
Based on immunogenicity preliminary data and DSMB recommendations, the two administrations of mid, high and top dose (prime-boost) or saline will continue.
The subjects will be followed for a period of up to 12 months post last vaccine administration to assess the safety and efficacy of the vaccine.
- ^ Clinical trial number NCT04608305 for “Phase I/II Randomized, Multi-Center, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Immunogenicity and Potential Efficacy of an rVSV-SARS-CoV-2-S Vaccine (IIBR-100) in Adults” at ClinicalTrials.gov
- ^ Jeffay N (29 December 2020). “As Israel goes vaccine-wild, will the homegrown version lose its shot?”. The Times of Israel. Retrieved 1 January 2021.
Israeli institute’s COVID vaccine candidate said very effective in animal trials
Secretive Israeli research center’s shot shows near 100% efficacy in non-human trials, is on par with US company Moderna’s candidate, TV report says
Israeli researchers at a top secret research center have made progress on a coronavirus vaccine that shows a high level of effectiveness in animals, according to a Friday TV report.
However, there is no guarantee that the vaccine under development will be effective in humans, or will be available soon.
The Israel Institute for Biological Research (IIBR), a secretive unit that works under the Prime Minister’s Office, developed a vaccine that shows close to 100 percent protection against the virus in lab animals, the Channel 12 report said, citing “a security source.”
The vaccine under development is on par in effectiveness with a vaccine being developed by US biotechnology company Moderna, the report said.
Unlike vaccines developed abroad, the domestic vaccine will first be delivered to Israeli citizens, it added. If successful, it was expected to provide protection against the disease with a single dose.
The institute has not started human trials but was preparing to manufacture 10 to 15 million doses, report said.
Hebrew media have reported on potential breakthroughs at the shadowy institute several times before, starting in mid-March, with the Defense Ministry pushing back on some of the claims to tamper expectations.
Magen David Adom medical workers test Israelis for the coronavirus at a drive-through site in Lod, on July 10, 2020. (Yossi Aloni/Flash90)
IIBR said last month that it had completed successful coronavirus vaccine trials on rodents, paving the way for further testing on other animals and then possibly human trials.
In a paper published on the website of bioRxiv, an online repository for papers that haven’t yet been peer-reviewed, the institute, which is based in Ness Ziona, said it hopes to have a finished vaccine in a year, or possibly even earlier.
In the abstract of the report, the researchers say their vaccine, which they tested on hamsters, “results in rapid and potent induction of neutralizing antibodies against SARS-CoV-2,” the virus that causes COVID-19.
Earlier this month a vaccine adviser to the government cautioned that there was no guarantee that the shots being developed will prove widely effective.
In May, the institute confirmed that it had isolated an antibody it believed could be used to develop treatments against the virus. The development would not be useful in the creation of a vaccine, but would rather be a move toward a drug treatment for those who have already contracted the disease.
Tal Zaks, Moderna’s Israeli chief medical officer, described to Channel 12 on Friday the company’s push into Phase 3 testing of its vaccine candidate, which was developed with the National Institutes of Health, and began its first injections Monday.
The trial, the world’s largest vaccine study, plans to test the vaccine on 30,000 volunteers.
There’s still no guarantee that the experimental vaccine, developed by the National Institutes of Health and Moderna Inc., will really offer protection.
“The first time we saw the first model, that the vaccine, even if it’s just in mice, successfully stimulated the immune system to identify the virus and neutralize it, I knew that we hadn’t missed anything, that we had the correct vaccine,” he said.
“And of course the second ‘ah-ha’ moment was when we saw the first clinical results, when it was clear that in humans we weren’t just getting to antibody levels we were seeing in sick people, which is what we aspired to, but we were getting to even higher levels,” Zaks said.
A Nurse gives a volunteer an injection, as the world’s biggest study of a possible COVID-19 vaccine, developed by the US National Institutes of Health and Moderna Inc., gets underway on July 27, 2020, in Binghamton, NY. (AP Photo/Hans Pennink)
Last month Israel signed a deal with Moderna for the potential purchase of its coronavirus vaccine if it ends up proving effective.
Moderna said the vaccination was administered in Savannah, Georgia, the first site to get underway among more than seven dozen trial sites scattered around the country.
Several other vaccines made by China and by Britain’s Oxford University earlier this month began smaller final-stage tests in Brazil and other hard-hit countries.
The massive studies aren’t just to test if the shots work — they’re needed to check each potential vaccine’s safety. And following the same study rules will let scientists eventually compare all the shots.
It normally takes years to create a new vaccine from scratch, but scientists are setting speed records this time around, spurred by knowledge that vaccination is the world’s best hope against the pandemic.
If everything goes right with the final studies, it still will take months for the first data to trickle in from the Moderna test, followed by the Oxford one.
Governments around the world are trying to stockpile millions of doses of those leading candidates so if and when regulators approve one or more vaccines, immunizations can begin immediately. But the first available doses will be rationed, presumably reserved for people at highest risk from the virus.
Coronavirus cases in Israel rose by 1,791 in 24 hours on Friday and the national death toll hit 512, according to the latest Health Ministry figures.
The total case count stood at 70,970, with 320 patients in serious condition, including 98 on ventilators. The number of recovered patients reached 43,850.
Israel has the fifth-highest number of new coronavirus infections per capita in the world, overtaking the United States, according to data compiled by a scientific publication based at Oxford University.
And while Israel has seen the number of new coronavirus cases rocket to more than 2,000 a day in recent weeks, a new Hebrew University report published on Thursday asserted that Israel has managed to gain control of the second wave of the coronavirus, thanks to a recent stabilization in the number of seriously and moderately ill patients.
The curve for seriously and moderately ill patients began to spike in late June before stabilizing in recent days, the researchers reported. They credited the restrictions imposed by the government in recent weeks to limit crowding for helping to flatten the curve.
According to the report, the death toll will climb by roughly 200 in the coming three weeks as a result of the high infection rate over the past month.
Experts have blamed a too-speedy reopening and the lack of an effective contact-tracing program as main factors in the virus resurgence, which has come as new daily coronavirus cases around the world have also reached record highs.
|Vaccine type||Viral vector|
|Part of a series on the|
|COVID-19 (disease)SARS-CoV-2 virus (variants)|
//////IIBR-100, Brilife, COVID-19, vaccine, israel, corona virus, covid 19, SARS-CoV-2
NEW DRUG APPROVALS
QazCovid-inVaccinePhase I/II/IIIThe QazCovid-in vaccine is an inactivated vaccine. Inactive viral vaccines are created by propagating viruses in cell culture (such as in Vero cells) and/or by inactivation using a chemical reagent (such as beta-propiolactone or formaldehyde). Upon vaccination, this allows the body to generate a diverse immune response against numerous viral antigens while having no threat of actually being infected because the virus is inactive.NEWS FEED December 31, 2020The Republic of Khazakstan’s QazCovid-in COVID19 vaccine enters phase 3 with an expected 3000 participants. August 28, 2020QazCovid-in, an inactive viral vaccine manufactured by Research Institute for Biological Safety Problems Republic of Kazakhstan enters Phase 1/2 clinical trials.ORGANIZATIONSResearch Institute for Biological Safety Problems, National Scientific Center for Phthisiopulmonology of the Republic of Kazakhstan, City polyclinic No. 4 of the UZO of Almaty, Clinic of the International Institute of Postgraduate Education, City Multidisciplinary Hospital of the Health Department of the Akimat of Zhambyl RegionCOUNTRIES INVOLVED TRIAL PARTICIPANTS
Phase 1: 44
Phase 2: 200
Phase 3: 3000CLINICAL TRIAL NUMBERNCT04530357NCT04691908
A new vaccine on the scene: Kazakhstan begins rollout of homegrown QazVac
The world’s approved COVID-19 vaccines have all come from large economies such as the U.S., China, the U.K., Russia, and India. Until today.
On Monday, Kazakhstan started rolling out its homegrown vaccine, now known as QazVac. Before a rebranding at the end of last month, it was called QazCovid-in, but the central Asian country’s government decided that name might be a turnoff for the public.
The vaccine was developed by Kazakhstan’s Research Institute for Biological Safety Problems, which claimed 96% efficacy in the second stage of clinical trials. The final phase is still ongoing, with a conclusion expected in July, but Kazakh health authorities decided it was fine to begin the rollout as long as the 3,000-participant Phase III trial was at least halfway finished.
This isn’t an adenovirus vector vaccine like those from Johnson & Johnson and AstraZeneca—though it does share their relatively mild refrigeration requirements—nor is it an mRNA-based jab like the BioNTech/Pfizer and Moderna vaccines. Instead, it uses an inactivated form of the SARS-CoV-2 virus itself, much like China’s CoronaVac and India’s Covaxin, which are both in use, and Valneva’s vaccine, which isn’t there yet. The QazVac regimen comprises two doses, to be administered three weeks apart.
‘Turn the tide’
Health Minister Alexei Tsoi was one of the first QazVac recipients on Monday morning. Tsoi was at the start of this month on the receiving end of a public dressing-down by President Kassym-Jomart Tokayev, who was furious about the sluggish start to the country’s inoculation campaign amid rising case numbers.
“You must turn the tide, otherwise a personnel decision that is going to be very disappointing for you will follow,” Tokayev told Tsoi. The vaccination campaign, which had previously focused on frontline workers, then reportedly sprang to life for others too in the oil-rich country.
Thus far, Kazakhstan’s vaccination drive has been powered by Russia’s Sputnik V, which has been produced locally for the past couple of months (Tokayev opted for the Russian shot, rather than waiting for QazVac). By late last week, just over 800,000 people had received their first dose. Kazakhstan has a population of 18.8 million people; the government plans to inoculate 2 million each month.
Tokayev tweeted Friday that domestic production would provide vaccine availability to all citizens. If so, that would be a remarkable turnaround—Almaty health officials said five weeks ago that the largest Kazakh city had run out of vaccines, and mass vaccination would not be realistic in the near future.
QazVac may have given Tokayev the opportunity to praise Kazakhstan’s scientific prowess, but production remains a bottleneck. The first batch to be distributed runs to only 50,000 doses, and the next tranche, to be produced in May, will be of the same volume.
Tsoi said Monday that the Kazakh government was talking to Turkish manufacturers about increasing production capacity.
QazCovid-in, commercially known as QazVac, is a COVID-19 vaccine developed by the Research Institute for Biological Safety Problems in Kazakhstan. QazCoVac-P is a second COVID-19 vaccine developed by the Kazakh Biosafety Research Institute and in clinical trials.
The administration of the vaccine for the general population began at the end of April 2021. The Research Institute Kunsulu Zakarya’s Director General’s justification is that the trial is almost 50% completed and “people who have received [the] vaccine feel well; there have been no side-effects and the effectiveness of the vaccine is high”.
The vaccine was first manufactured by Kazakhstan’s Research Institute of Biological Safety Problems. Production capacity has been capped at 50,000 doses per month.
Beginning in June 2021, the vaccine is slated to be packaged in large bulk to be bottled in Turkey by a major Turkish company. This will allow for a production capacity of 500,000-600,000 doses per month. The contract is still being negotiated, despite earlier claims that suggesting the deal had already been finalized.
The first batch of 50,000 doses was delivered on 26 April 2021, and vaccination began shortly after. In June 2021, the capacity will increase to 100,000 doses per month, regardless of the contract for bottling in Turkey.
|Full authorization Emergency authorization|
The vaccine can be stored at standard refrigeration temperatures (2°C-8°C) and is a two-dose régime with the doses administered twenty-one days apart.
- ^ “Kazakhstan: Officials under fire over vaccination failures | Eurasianet”. eurasianet.org. Retrieved 11 April 2021.
- ^ INFORM.KZ (31 March 2021). “Vaccination with homegrown QazVac vaccine likely to start in late April”. http://www.inform.kz. Retrieved 11 April 2021.
- ^ Yergaliyeva A (20 December 2020). “Kazakhstan Begins Vaccinating 3,000 Volunteers With Self-Made QazCovid-in”. The Astana Times. Retrieved 2 March2021.
- ^ Clinical trial number NCT04691908 for “Immunogenicity, Efficacy and Safety of QazCovid-in® COVID-19 Vaccine” at ClinicalTrials.gov
- ^ “Reactogenicity, Safety and Immunogenicity of QazCovid-in® COVID-19 Vaccine – Full Text View – ClinicalTrials.gov”. clinicaltrials.gov.
- ^ “Kazakh Biosafety Research Institute Begins Clinical Trials of Another Vaccine Against COVID-19”. The Astana Times.
- ^ INFORM.KZ (31 March 2021). “Vaccination with homegrown QazVac vaccine likely to start in late April”. http://www.inform.kz. Retrieved 11 April 2021.
- ^ “QazVac готова и уже на подходе”. Время (in Russian). Retrieved 11 April2021.
- ^ INFORM.KZ (9 April 2021). “3rd stage of clinical trials of QazCovid-in vaccine to be 50% complete by Apr 15”. http://www.inform.kz. Retrieved 11 April 2021.
- ^ “Kazakhstan’s COVID-19 vaccine to be bottled in Turkey”. http://www.aa.com.tr. Retrieved 11 April 2021.
- ^ tengrinews.kz (9 April 2021). “Как правильно применять казахстанскую вакцину QazVac, рассказал ученый”. Главные новости Казахстана – Tengrinews.kz (in Russian). Retrieved 11 April 2021.
- ^ “QazVac готова и уже на подходе”. Время (in Russian). Retrieved 11 April2021.
- ^ It’s unclear at which level of preparation the vaccine will be send to Turkey.
- ^ MENAFN. “Kazakh COVID-19 vaccine to be bottled in Turkey”. menafn.com. Retrieved 11 April 2021.
- ^ “QazVac готова и уже на подходе”. Время (in Russian). Retrieved 11 April2021.
- ^ “Kazakhstan Launches Production of First Homegrown Vaccine, ‘QazVac'”. caspiannews.com. Retrieved 26 April 2021.
- ^ INFORM.KZ (21 April 2021). “Healthcare Ministry comments on production of QazVac vaccine”. http://www.inform.kz. Retrieved 22 April 2021.
- ^ “К концу апреля в Казахстане будет выпущено 50000 доз собственной вакцины”. “СНГ СЕГОДНЯ” – последние новости стран СНГ читайте на SNG.TODAY. Retrieved 12 April 2021.
- ^ “Kazakhstan’s COVID-19 vaccine to be bottled in Turkey”. http://www.aa.com.tr. Retrieved 12 April 2021.
- ^ contributor, Guest (26 April 2021). “Kazakhstan launches QazVac, its own COVID-19 vaccine”. EU Reporter. Retrieved 26 April 2021.
- ^ “Казахстанскую вакцину QazVac будут разливать в Турции”. informburo.kz(in Russian). 9 April 2021. Retrieved 12 April 2021.
- ^ INFORM.KZ (26 April 2021). “Health Minister Alexei Tsoi to be one of the first to get homegrown QazCovid-in vaccine”. http://www.inform.kz. Retrieved 26 April 2021.
The QazCovid-in vaccine, an inactivated vaccine, was developed and tested in the Kazakh Research Institute for Biological Safety Problems1. It demonstrated high efficacy, safety, and immunogenicity at 96% in initial Phase I and II trials (NCT04530357), and will now be undergoing upcoming Phase III trials2,3.
- The Astana Times: Kazakhstan Begins Vaccinating 3,000 Volunteers With Self-Made QazCovid-in [Link]
- The Lancet: COVID-19 response in central Asia [Link]
- Economic Research Institute: QazCovid-in [Link]
|Part of a series on the|
|COVID-19 (disease)SARS-CoV-2 virus (variants)|
///////////QazVac, COVID 19, vaccine, QazCovid-in, kazakhastan, SARS-CoV-2, corona virus
NEW DRUG APPROVALS
Origin of EpiVacCorona antigenes
- MKIEEGKLVIWINGDKGYNGLAEVGKKFEKDTGIKVTVEHPDKLEEKFPQVAATGDGPDIIFWAHDRFGGYAQSGLLAEITPDKAFQDKLYPFTWDAVRYNGKLIAYPIAVEALSLIYNKDLLPNPPKTWEEIPALDKELKAKGKSALMFNLQEPYFTWPLIAADGGYAFKYENGKYDIKDVGVDNAGAKAGLTFLVDLIKNKHMNADTDYSIAEAAFNKGETAMTINGPWAWSNIDTSKVNYGVTVLPTFKGQPSKPFVGVLSAGINAASPNKELAKEFLENYLLTDEGLEAVNKDKPLGAVALKSYEEELAKDPRIAATMENAQKGEIMPNIPQMSAFWYAVRTAVINAASGRQTVDEALKDAQTNSSSNNNNNNNNNNLGDNGPQNQRNAPRITFGGPSDSTGSNQNGERSGARSKQRRPQGLPNNTASWFTALTQHGKEDLKFPRGQGVPINTNSSPDDQIGYYRRATRRIRGGDGKMKDLSPRWYFYYLGTGPEAGLPYGANKDGIIWVATEGALNTPKDHIGTRNPANNAAIVLQLPQGTTLPKGFYAEGSRGGSQASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGGDAALALLLLDRLNQLESKMSGKGQQQQGQTVTKKSAAEASKKPRQKRTATKAYNVTQAFGRRGPEQTQGNFGDQELIRQGTDYKHWPQIAQFAPSASAFFGMSRIGMEVTPSGTWLTYTGAIKLDDKDPNFKDQVILLNKHIDAYKTFPPTEPKKDKKKKADETQALPQRQKKQQTVTLLPAADLDDLSKQLQQSMSSADSTQA. “Carrier protein sequence”.
Federal Budgetary Research Institution State Research Center of Virology and Biotechnology
PATENT https://www.fips.ru/registers-doc-view/fips_servlet?DB=RUPAT&DocNumber=2743594&TypeFile=htmlRU 2 743 594 RU 2 743 593RU 2 743 595 RU 2 738 081 Science (Washington, DC, United States) (2021), 372(6538), 116-117.
EpiVacCorona (Russian: ЭпиВакКорона, tr. EpiVakKorona) is a peptide-based vaccine against COVID-19 developed by the VECTOR center of Virology. It consists of three chemically synthesized peptides (short fragments of a viral spike protein) that are conjugated to a large carrier protein. This protein is a fusion product of a viral nucleocapsid protein and a bacterial MBP protein.The third phase of a clinical trial, which should show whether the vaccine is able to protect people from COVID-19 or not, was launched in November 2020 with more than three thousand participants. It is assumed it will be completed in August 2021. According to the vaccine developers, the peptides and the viral part of the chimeric protein should immunize people who received this vaccine against SARS-CoV-2 and trigger the production of protective antibodies. However, some experts in the field have expressed concerns about the selection of peptides for use as vaccine antigens. In addition, there are also serious concerns about the vaccine immunogenicity data, which have fueled independent civic research efforts and criticism by some experts. Meanwhile, the EpiVacCorona has received vaccine emergency authorization in a form of government registration and is available for vaccination outside the clinical trials. The vaccine delivered via intramuscular route and aluminum hydroxide serves as an immunological adjuvant.
Origin of EpiVacCorona antigenes
The vaccine includes three chemically synthesized short fragments of the viral spike protein – peptides, which, according to the developers of EpiVacCorona represent the protein regions containing B-cell epitopes that should be recognized by the human immune system.
These peptides are represented by following amino acid sequences:
In the vaccine all peptides are conjugated to a carrier protein, which is an expression product of the chimeric gene. This chimeric gene was created by fusion of two genes originating from different organisms, namely a gene encoding a viral nucleocapsid protein and a gene encoding a bacterial maltose-binding protein (MBP). The fusion chimeric gene expressed in Escherichia coli. The sequence of the chimeric protein is available from the patent. The genetic construct of the chimeric gene also includes a short genetic fragment encoding a polyhistidine-tag, which is used to purify the chimeric protein from E. coli lysate. After the purification, the protein is conjugated with three peptides in a way that only one variant of the peptide molecule is attached to each protein molecule. As a result, three types of conjugated molecules are created: chimeric protein with attached peptide number 1, the same protein with peptide number 2, and finally the same protein with peptide number 3. All three types of conjugated molecules are included in the vaccine.
EpiVacCorona: antigens origin and composition
Vaccine antigens and antibodies
According to the developers’ publications, vaccine antigens are three peptides of the spike protein and a chimeric protein consisting of two parts (viral nucleocapsid protein and bacterial maltose-binding protein). In addition, the polyhistidine-tag – a short peptide that is introduced into a vaccine composition to purify a chimeric protein from a bacterial lysate – is also a vaccine antigen against which antibodies can form in those who have received the vaccine. A person vaccinated with EpiVacCorona can develop antibodies not only to the peptides of the spike protein, but also to other antigens present in the vaccine. According to Anna Popova who is a head of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare, it takes 42 days for those vaccinated with EpiVacCorona to develop immunity.
Immunogenic peptide screening in rabbits for EpiVacCorona design
The primary screening of peptides for the search for the most immunogenic ones was carried out in animals. The level of antibodies that was triggered by each tested peptide after administration to rabbits was measured. In the test, hemocyanin protein was used as a carrier protein for the studied peptides. Further, on six species of animals (mice, rats, rabbits, African green monkeys, rhesus monkeys, guinea pigs), the vaccine was shown to be harmless in terms of such parameters as general toxicity, allergic properties, and mutagenic activity. In four species of animals (hamsters, ferrets, African green monkeys, rhesus monkeys), specific activity was shown: immunogenicity and protective properties against SARS-CoV-2. The main results of preclinical studies are published in the “Bulletin of the Russian Academy of Medical Sciences”.
The trial “Study of the Safety, Reactogenicity and Immunogenicity of “EpiVacCorona” Vaccine for the Prevention of COVID-19 (EpiVacCorona)” was registered in clinical trial database with ClinicalTrials.gov identifier: NCT04780035. Another trial with the same title was registered with ClinicalTrials.gov Identifier: NCT04527575. Results of the trial that included data on 86 participants were published in Russian Journal of Infection and Immunity, indicating preliminary evidence of safety and an immune response. The publication reports preliminary results of the first two phases of clinical trials of the vaccine in volunteers, of which 14 people aged 18-30 years participated in the first phase, and 86 volunteers aged 18-60 years in the second phase. It is claimed that antibodies were formed in 100% of the volunteers, and the vaccine is also claimed to be safe.
EpiVacCorona Vaccine Development Timeline
The third phase of a clinical trial, which should show whether the vaccine is able to protect people from COVID-19 or not, was launched in November 2020 with more than three thousand participants planned. It is expected to be completed in September 2021. In the clinical trials database the phase III trial etitled “Study of the Tolerability, Safety, Immunogenicity and Preventive Efficacy of the EpiVacCorona Vaccine for the Prevention of COVID-19” was registered only in March 2021 with ClinicalTrials.gov Identifier: NCT04780035. Phase 3-4 trial was registered in Russia at 18.11.2020 with 4991 participants planned.
The following patents of the Russian Federation for invention have been published, which protect the EpiVacCorona vaccine:
“Peptide immunogens and vaccine composition against coronavirus infection COVID-19 using peptide immunogens” (No. 2738081). There are 7 peptides in patented vaccine compositions.
“Peptide immunogens and vaccine composition against coronavirus infection COVID-19 using peptide immunogens” (No. 2743593). The patented vaccine composition contains 2 peptides.
“Peptide immunogens used as a component of a vaccine composition against coronavirus infection COVID-19″ (No. 2743594). The patented vaccine composition contains 3 peptides.
“Vaccine composition against coronavirus infection COVID-19″ (No. 2743595). The patented vaccine composition contains 3 peptides.
In all of these patents, the carrier protein is referred to as a chimeric fusion protein with an amino acid sequence derived from two parts, a bacterial maltose binding protein and a viral nucleocapsid protein.
EpiVacCorona vaccine registration certificate
Full authorization Emergency authorization
The VECTOR has received vaccine emergency authorization in a form of government registration in October 2020.
In Russia phase III clinical study is called post-registration study. Therefore, government registration of the vaccine means permission to perform phase III clinical research and public vaccination outside of clinical trials as well. Since December 2020, the vaccine has been released for public vaccination in Russia.
Russia’s Chief Health Officer Anna Popova said: “In December 2020 the EpiVacCorona documents were presented to the World Health Organization, and we are expecting a decision from WHO.” However, Deutsche Welle reports “As of March 1, the WHO had yet to receive an Expression of Interest (EOI) from EpiVacCorona’s developers, “VECTOR,” to enable WHO experts to evaluate their vaccine.”
The Deputy Director-General of the World Health Organization (WHO) Dr. Soumya Swaminathan during news conference in Geneva that took place in October 2020, told: “We will only be able to have a position on a vaccine when we see results of the phase III clinical trials.” According to the center’s director Rinat Maksyutov, many government and non-government organizations want to test or be involved in the production of the vaccine. As of March 30, Venezuela obtained 1000 doses of the Russian EpiVacCorona vaccine for a trial. Venezuela also has reached a deal to purchase doses of the vaccine, as well as manufacture it locally, Vice President Delcy Rodriguez provided this information on June 4, 2021. Turkmenistan expects to receive EpiVacCorona, as the vaccine has already been approved for use in that country.
Independent study of clinical trial participants
Ministry of Health’s response to a request from trial participants to perform independent antibody screening tests
English translation of Ministry of Health’s response to a request from trial participants to perform independent antibody screening tests.
At the start of the Phase III, trial participants and those vaccinated outside the trial began to form a community through the Telegram messenger network. On January 18, 2021, the members of the community turned to the Ministry of Health of the Russian Federation with an open letter, in which they stated that the production of antibodies after vaccination among them is much lower than declared by vaccine developers. Study participants claimed that antibodies were not found in more than 50% of those who documented their participation in the study, although only 25% of the participants should have had a placebo according to the study design. The trial participants also claimed that negative results were obtained using the a special ELISA test developed and recommended by VECTOR for EpiVacCorona detection. More questions about the quality and protectiveness of antibodies induced by EpiVacCorona appeared along with the first results of a special antibody VECTOR’s test, when, with a positive special test, negative results of all other commercially available tests were otained: LIAISON SARS-CoV-2 S1 / S2 IgG – DiaSorin, IgM / IgG – Mindray, SARS-CoV-2 IgG – Abbott Architect, Anti-SARS-CoV-2 ELISA (IgG) – Euroimmun, Access SARS-CoV-2 IgG (RBD) – Beckman Coulter, “SARS-CoV-2-IgG-ELISA -BEST “-” Vector-Best “,” Anti-RBD IgG “- Gamaleya Research Center. Clinical trial participants conducted their own antibody mini-study that was performed in independent Russian laboratory. The study participants asked Dr. Alexander Chepurnov, the former head of the infectious diseases department at VECTOR, who now works at another medical institute, to check neutralizing antibodies presence in their serum samples. They also sent to Dr. Chepurnov control serum samples from former COVID-19 patients or people vaccinated with another Russian vaccine, Sputnik V, which is known to trigger the production of neutralizing antibodies. All serum samples were blinded before antibody tests. On 23 March 2021, the participants reported the results of their mini-study in an open letter to the Ministry of Health of the Russian Federation. According to the letter, even with the help of the VECTOR antibody detection system, antibodies were detected only in 70-75% of those vaccinated with EpiVacCorona. However, the level of antibodies was very low. Moreover, according to the letter, virus-neutralizing antibodies were not detected in the independent research Dr. Alexander Chepurnov laboratory at all. The trial participants asked Ministry of Health in their open letter to perform independent study for the verification of their findings. In addition, the letter reports 18 cases of COVID-19 cases as of March 22, 2021 among those who received the vaccine and became ill (sometimes severe) three weeks or later after the second dose of EpiVacCorona. April 20, 2021 the study participants got a reply, with refusal of performing any additional verification antibody tests or investigation of sever COVID-19 cases among vaccinated individuals. The reply include the following text: “Considering that the listed immunobiological preparations (vaccines) for the prevention of COVID-19 are registered in the prescribed manner, their effectiveness and safety have been confirmed.”
Vaccine criticism by independent experts
Some independent experts criticized the vaccine design and clinical data presentation in the publication. The experts are saying that peptide selection is “crucial” for the innovative peptide approach, which VECTOR uses for EpiVacCorona design. However, some researchers are not convinced that the viral spike protein peptides selected for the vaccine are actually “visible” by human immune system. They stated that these peptides do not overlap with peptides that have been shown in several publications to contain human linear B cell epitopes in spike protein of SARS-CoV-2. Moreover, the study was criticized for the lack of positive control of convalescent plasma samples in reports related to neutralizing antibody titers in vaccinated individuals. The same study was also criticized for presence of detectable antibodies in negative controls samples that were not discussed by authors. In addition, vaccine developers have been criticized for aggressively advertising their vaccine efficacy prior to the completion of phase III clinical trial. The most substantial criticism came from Dr. Konstantin Chumakov, who currently serves as the Associate Director for Research at the FDA Office of Vaccines Research and Review. Dr. Chumakov said: “I would not be in a hurry to call this peptide formulation a vaccine yet, because its effectiveness has not yet been proven…For the introduction of such a vaccine, the level of evidence must be much higher, and therefore the developers of EpiVacCorona, before launching their vaccine on the market, had to conduct clinical trials and prove that their vaccine actually protects against the disease. However, such tests were not carried out, which is absolutely unacceptable.”
The title page of the “EpiVacCorona” patent with Anna’s Popova name among inventors
Conflict of interest
The vaccine design was protected by several already issued patents (see section above). In each patent one of its co-authors is a namesake of Anna Popova who is a head of the Federal Service for Supervision of Consumer Rights Protection and Human Welfare. This patent authorship represents an issue as far as Anna Popova is a head of the Russian agency that is charged with overseeing vaccine safety and efficacy. As a co-author of these patents, she might have an interest in promoting the vaccine despite its shortcomings.
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- ^ Реестр Клинических исследований COV/pept-03/20; 
- ^MKIEEGKLVIWINGDKGYNGLAEVGKKFEKDTGIKVTVEHPDKLEEKFPQVAATGDGPDIIFWAHDRFGGYAQSGLLAEITPDKAFQDKLYPFTWDAVRYNGKLIAYPIAVEALSLIYNKDLLPNPPKTWEEIPALDKELKAKGKSALMFNLQEPYFTWPLIAADGGYAFKYENGKYDIKDVGVDNAGAKAGLTFLVDLIKNKHMNADTDYSIAEAAFNKGETAMTINGPWAWSNIDTSKVNYGVTVLPTFKGQPSKPFVGVLSAGINAASPNKELAKEFLENYLLTDEGLEAVNKDKPLGAVALKSYEEELAKDPRIAATMENAQKGEIMPNIPQMSAFWYAVRTAVINAASGRQTVDEALKDAQTNSSSNNNNNNNNNNLGDNGPQNQRNAPRITFGGPSDSTGSNQNGERSGARSKQRRPQGLPNNTASWFTALTQHGKEDLKFPRGQGVPINTNSSPDDQIGYYRRATRRIRGGDGKMKDLSPRWYFYYLGTGPEAGLPYGANKDGIIWVATEGALNTPKDHIGTRNPANNAAIVLQLPQGTTLPKGFYAEGSRGGSQASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGGDAALALLLLDRLNQLESKMSGKGQQQQGQTVTKKSAAEASKKPRQKRTATKAYNVTQAFGRRGPEQTQGNFGDQELIRQGTDYKHWPQIAQFAPSASAFFGMSRIGMEVTPSGTWLTYTGAIKLDDKDPNFKDQVILLNKHIDAYKTFPPTEPKKDKKKKADETQALPQRQKKQQTVTLLPAADLDDLSKQLQQSMSSADSTQA. “Carrier protein sequence”.
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- Margarita Romanenko’s Lecture about Russian Covid-vaccines
- Meduza – Interview with EpiVacCorona developers, 23 March 2021
- Infection and Immunity – Study of the safety, reactogenicity and immunogenecity of the “EpiVacCorona” vaccine (PHASE I–II)
|Vaccine type||Peptide subunit|
|Legal status||Registered in Russia on 14 October 2020 RU Registered.TU approved.Full list : List of EpiVacCorona COVID-19 vaccine authorizations|
|Part of a series on the|
|COVID-19 (disease)SARS-CoV-2 (virus)|
EpiVacCorona Vaccine, developed by the Vektor State Research Center of Virology and Biotechnology in Russia, is based on peptide-antigens that facilitate immunity to the SARS-CoV-2 virus1. It is currently being tested in Phase I/II clinical trials for safety and immunogenicity (NCT04527575)1,2.
- Precision Vaccinations: VACCINE INFO EpiVacCorona Vaccine [Link]
- The Pharma Letter: Russia’s EpiVacCorona vaccine post-registration trials started [Link]
//////EpiVacCorona, SARS-CoV-2, RUSSIA, CORONA VIRUS, COVID 19, VACCINE, PEPTIDE
NEW DRUG APPROVALS
A COVID-19 vaccine comprising a dimeric form of SARS-CoV-2 receptor-binding domain (RBD) produced in China hamster ovary (CHO) cells and adjuvanted with aluminum hydroxide (Anhui Zhifei Longcom/Institute of Microbiol. China Academy of Sciences)
Anhui Zhifei Longcom Biopharmaceutical, Institute of Microbiology of the Chinese Academy of Sciences
CHO Cells Recombinant Vaccine
- Chinese Academy of Sciences (Originator)
- Zhifei Longcom (Originator)
Human SARS-CoV-2 (Covid-19 coronavirus) vaccine consisting of recombinant dimer comprising two RBD domains (R319-K527) of the spike glycoprotein of SARS-CoV-2 fused via a disulfide link; expressed in CHO cells
ZF-2001 is a recombinant coronavirus vaccine jointly developed by the Institute of Microbiology of the Chinese Academy of Sciences and Zhifei Longcom. The vaccine became available in 2021 in Uzbekistan under an emergency use authorization for the prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19). The vaccine is currently evaluated in phase III clinical trials.
This vaccine candidate, developed in China, uses SARS-CoV-2 protein subunits that are entirely engineered, created, and secreted by Chinese Hamster Ovary (CHO) cells1. The vaccine candidate is sponsored by Anhui Zhifei Longcom Biologic Pharmacy Co., Ltd. and is undergoing phase I clinical trials to evaluate safety and tolerability.
ZF2001, trade-named ZIFIVAX, is an adjuvanted protein subunit COVID-19 vaccine developed by Anhui Zhifei Longcom in collaboration with the Institute of Microbiology at the Chinese Academy of Sciences. As of December 2020, the vaccine candidate was in Phase III trials with 29,000 participants in China, Ecuador, Malaysia, Pakistan, and Uzbekistan.
ZF2001 was first approved for use in Uzbekistan and later China. Production capacity is expected to be one billion doses a year. Phase II results published in The Lancet on the three dose administration showed seroconversion rates of neutralizing antibodies of between 92% to 97%.
Anhui Zhifei Longcom Biopharmaceuticals began a phase 3 clinical trial for its recombinant protein vaccine candidate in December, according to the WHO. State-run China Global Television Network in November reported that a one-year trial would take place in Uzbekistan and aim to recruit 5,000 volunteers. Anhui Zhifei is a unit of private firm Chongqing Zhifei Biological Products. It is co-developing the vaccine with the Chinese Academy of Sciences, a government institution.
Emergency Use Authorization received in UZ by Zhifei Longcom for the prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19)
As described in Cell, the CoV spike receptor-binding domain (RBD) is an attractive vaccine target for coronaviruses but is constrained by limited immunogenicity, however a dimeric form of MERS-CoV RBD offers greater protection. The RBD-dimer significantly increases neutralizing antibodies compared to a conventional monomeric form and protected mice against MERS-CoV infection. CoV RBD-dimer have been produced at high yields in pilot scale production.
Rather than injecting a whole virus, subunit vaccines contains virus particles specially selected to stimulate an immune response. Because the fragments are incapable of causing disease, subunit vaccines are considered very safe. Subunit vaccines in widespread use include the Hepatitis B vaccine and Pertussis vaccine. However, as only a few viral components are included in the vaccine which does not display the full complexity of the virus, their efficacy may be limited. Subunit vaccines are delivered alongside adjuvants and booster doses may be required.
According to industry experts, production for this kind of vaccine is stable and reliable, and easier to achieve large-scale industrial production at home and overseas. However it was noted it can be very inconvenient for people to come back for a second and third dose.
ZF2001 (Anhui Zhifei Longcom Biopharmaceutical/Chinese Academy of Medical Sciences)
The latest subunit vaccine candidate to enter Phase 3 clinical studies is the adjuvanted RBD-dimeric antigen designed by Anhui Zhifei Longcom Biopharmaceutical and the Institute of Microbiology of the Chinese Academy of Medical Sciences. Phase 3 clinical study was launched on December104 and will be initially carried out in China and Uzbekistan while Indonesia, Pakistan and Ecuador will follow as study sites (Clinical Trial Identifier: NCT04646590 and Registration Number: ChiCTR2000040153). The design of the study involves recruitment of 22,000 volunteers from China and 7000 subjects outside China for a total of 29,000 volunteers. There are still no published results on this candidate, however data from its Phase 2 placebo-controlled clinical trial (Clinical Trial Identifier: NCT04466085) conducted on a total of 900 participants ranging from 18 to 59 years old suggest that a 2 or 3 dose regimen is evaluated. Each immunization will be separated by the next by 4 weeks.
Phase I and II trials and results
In July, Longcom began a randomized, double-blind, placebo-controlled Phase II trial with 900 participants aged 18–59 in Changsha, Hunan divided into low-dose, high-dose, and placebo groups. In August, an additional Phase II trial was launched with 50 participants aged 60 and above.
In Phase II results published in The Lancet, on the two-dose schedule, seroconversion rates of neutralizing antibodies after the second dose were 76% (114 of 150 participants) in a 25 μg group and 72% (108 of 150) in a 50 μg group. On the three-dose schedule, seroconversion rate of neutralizing antibodies after the third dose were 97% (143 of 148 participants) in the 25 μg group and 93% (138 of 148) in the 50 μg group. 7 to 14 days after the administration of the third dose, the GMTs of neutralizing antibodies reached levels that were significantly higher than observed in human convalescent serum of recovering COVID-19 patients, especially in the 25 μg group.
Phase III trials
In December, Longcom began enrollment of a Phase III randomized, double-blind, placebo-controlled clinical trial for 29,000 participants, including 750 participants between 18-59 and 250 participants 60 and older in China and 21,000 participants between 18-59 and 7,000 participants 60 and older outside China.
In February, Pakistan‘s Drug Regulatory Authority (DRAP) approved Phase III trials with approximately 10,000 participants to be conducted at UHS Lahore, National Defense Hospital, and Agha Khan Hospital.
In February, lab studies of twelve serum samples taken from recipients of BBIBP-CorV and ZF2001 retained neutralizing activity against the Beta variant although with weaker activity than against the original virus. For ZF-2001, geometric mean titers declined by 1.6-fold, from 106.1 to 66.6, which was less than antisera from mRNA vaccine recipients with a 6-folds decrease. Preliminary clinical data from Novavax and Johnson & Johnson also showed they were less effective in preventing COVID-19 in South Africa, where the new variant is widespread.
The company’s vaccine manufacturing facility was put into use in September. In February 2021, Pu Jiang, General Manager of Zhifei Longcom, said the company had an annual production capacity of 1 billion doses.
Marketing and deployment
Full authorization Emergency authorization
On March 1, Uzbekistan granted approval for ZF2001 (under tradename ZF-UZ-VAC 2001) after having taken part in the Phase III trials. In March, Uzbekistan received 1 million doses and started vaccinations in April. By May, a total of 3 million doses had been delivered.
On March 15, China approve of ZF2001 for emergency use after being approved by Uzbekistan earlier in the month.
- ^ Jump up to:a b “Anhui Zhifei Longcom: RBD-Dimer – COVID19 Vaccine Tracker”. covid19.trackvaccines.org. Retrieved 27 December2020.
- ^ “COVID-19 Vaccine: ZIFIVAX by Anhui Zhifei Longcom Biopharma, Institute of Microbiology Chinese Academy of Sciences”. covidvax.org. Retrieved 27 December 2020.
- ^ “Fifth Chinese Covid-19 vaccine candidate ready to enter phase 3 trials”. South China Morning Post. 20 November 2020. Retrieved 27 December 2020.
- ^ Jump up to:a b Ying TP (7 December 2020). “MYEG to conduct phase 3 clinical trial for China’s Covid-19 vaccine in Msia | New Straits Times”. NST Online. Retrieved 27 December 2020.
- ^ Zimmer C, Corum J, Wee SL (10 June 2020). “Coronavirus Vaccine Tracker”. The New York Times. ISSN 0362-4331. Retrieved 27 December 2020.
- ^ Jump up to:a b c d “China’s production bottleneck ‘could be eased with latest Covid-19 vaccine'”. South China Morning Post. 17 March 2021. Retrieved 18 March 2021.
- ^ Jump up to:a b Liu, Roxanne (15 March 2021). “China IMCAS’s COVID-19 vaccine obtained emergency use approval in China”. Reuters. Retrieved 15 March 2021.
- ^ Jump up to:a b Mamatkulov, Mukhammadsharif (1 March 2021). “Uzbekistan approves Chinese-developed COVID-19 vaccine”. Reuters. Retrieved 2 March 2021.
- ^ Jump up to:a b Yang, Shilong; Li, Yan; Dai, Lianpan; Wang, Jianfeng; He, Peng; Li, Changgui; Fang, Xin; Wang, Chenfei; Zhao, Xiang; Huang, Enqi; Wu, Changwei (24 March 2021). “Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials”. The Lancet Infectious Diseases. 0. doi:10.1016/S1473-3099(21)00127-4. ISSN 1473-3099. PMC 7990482. PMID 33773111.
- ^ Dai L, Zheng T, Xu K, Han Y, Xu L, Huang E, et al. (August 2020). “A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS”. Cell. 182 (3): 722–733.e11. doi:10.1016/j.cell.2020.06.035. PMC 7321023. PMID 32645327.
- ^ Jump up to:a b “What are protein subunit vaccines and how could they be used against COVID-19?”. http://www.gavi.org. Retrieved 27 December2020.
- ^ Dong Y, Dai T, Wei Y, Zhang L, Zheng M, Zhou F (October 2020). “A systematic review of SARS-CoV-2 vaccine candidates”. Signal Transduction and Targeted Therapy. 5 (1): 237. doi:10.1038/s41392-020-00352-y. PMC 7551521. PMID 33051445.
- ^ Clinical trial number NCT04445194 for “Phase I Clinical Study of Recombinant Novel Coronavirus Vaccine” at ClinicalTrials.gov
- ^ Clinical trial number NCT04466085 for “A Randomized, Blinded, Placebo-controlled Trial to Evaluate the Immunogenicity and Safety of a Recombinant New Coronavirus Vaccine (CHO Cell) With Different Doses and Different Immunization Procedures in Healthy People Aged 18 to 59 Years” at ClinicalTrials.gov
- ^ Clinical trial number NCT04550351 for “A Randomized, Double-blind, Placebo-controlled Phase I Clinical Trial to Evaluate the Safety and Tolerability of Recombinant New Coronavirus Vaccines (CHO Cells) in Healthy People Aged 60 Years and Above” at ClinicalTrials.gov
- ^ Clinical trial number NCT04646590 for “A Phase III Randomized, Double-blind, Placebo-controlled Clinical Trial in 18 Years of Age and Above to Determine the Safety and Efficacy of ZF2001, a Recombinant Novel Coronavirus Vaccine (CHO Cell) for Prevention of COVID-19” at ClinicalTrials.gov
- ^ Jump up to:a b c “Another Chinese Covid-19 vaccine enters late-stage human trials with a plan to produce 300 million doses annually”. Business Insider. Retrieved 27 December 2020.
- ^ Reuters Staff (11 November 2020). “Uzbekistan to carry out late-stage trial of Chinese COVID-19 vaccine candidate”. Reuters. Retrieved 27 December 2020.
- ^ “Uzbekistan poised to start trials on Chinese COVID-19 vaccine | Eurasianet”. eurasianet.org. Retrieved 27 December 2020.
- ^ “Ecuador participará en ensayos de una vacuna china contra el covid-19”. CNN (in Spanish). 29 December 2020. Retrieved 23 January 2021.
- ^ “China’s third vaccine enters Pakistan”. The Nation. 15 February 2021. Retrieved 28 February 2021.
- ^ “Covid vaccine tracker: How do the leading jabs compare?”. http://www.ft.com. 23 December 2020. Retrieved 27 December 2020.
- ^ Jump up to:a b Liu, Roxanne (3 February 2021). “Sinopharm’s COVID-19 vaccine remained active against S.Africa variant, effect reduced – lab study”. Reuters. Retrieved 29 March 2021.
- ^ Huang, Baoying; Dai, Lianpan; Wang, Hui; Hu, Zhongyu; Yang, Xiaoming; Tan, Wenjie; Gao, George F. (2 February 2021). “Neutralization of SARS-CoV-2 VOC 501Y.V2 by human antisera elicited by both inactivated BBIBP-CorV and recombinant dimeric RBD ZF2001 vaccines”. bioRxiv: 2021.02.01.429069. doi:10.1101/2021.02.01.429069.
- ^ uz, Kun. “Uzbekistan receives 1 million doses of ZF-UZ-VAC 2001 vaccine”. Kun.uz. Retrieved 28 March 2021.
- ^ Romakayeva, Klavdiya (18 May 2021). “Uzbekistan receives third batch of Chinese-Uzbek COVID-19 vaccine”. Trend.Az. Retrieved 19 May 2021.
|Vaccine type||Protein subunit|
|Part of a series on the|
|COVID-19 (disease)SARS-CoV-2 (virus)|
////////ZF2001, ZIFIVAX, corona virus, covid 19, SARS-CoV-2, ZF 2001, ZF-UZ-VAC2001, Uzbekistan, approvals 2021
NEW DRUG APPROVALS
CAS Registry Number: 64-86-8CAS Name:N-[(7S)-5,6,7,9-Tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl]acetamideMolecular Formula: C22H25NO6Molecular Weight: 399.44
CSIR-Laxai Life Sciences get DCGI nod for clinical trials Colchicine on Covid patients
It is an important therapeutic intervention for Covid-19 patients with cardiac co-morbidities and also for reducing proinflammatory cytokines
The Council of Scientific & Industrial Research (CSIR), and Laxai Life Sciences Pvt. Ltd. Hyderabad, have obtained approval from the Drug Controller General of India (DCGI) to undertake a two-arm phase-II clinical trial of the drug Colchicine for Covid-19 treatment.
The partner CSIR institutes in this important clinical trial are the CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad and CSIR-Indian Institute of Integrative Medicine (IIIM), Jammu.
According to Ram Vishwakarma, advisor to DG-CSIR, colchicine, in combination with standard of care, will be an important therapeutic intervention for Covid-19 patients with cardiac co-morbidities and also for reducing proinflammatory cytokines, leading to faster recovery.
A number of global studies have confirmed now that cardiac complications during the course of Covid-19 infections and post-covid syndrome are leading to the loss of many lives, and it is essential to look for new or repurposed drugs.
CHAIRMAN AND MD, LAXAI
A visionary & an entrepreneur with 17 years of experience in technology and bio-pharma industries. Founder and ex-CEO of LAXAI Pharma Ltd – a clinical data services company based in NJ, USA. Past employment: Pfizer, Wyeth Pharmaceuticals, Johnson & Johnson and Deloitte.
Vamsi provides a unique blend of operational and financial experience – along with a strong and expansive network of key influencers, industry experts and financial partners. He delivers a visionary understanding of client challenges and opportunities, and the instinctive ability to facilitate collaboration between the right people to turn strategic concepts into actionable plans – and, ultimately, into business results.
Dr S Chandrasekhar (Director CSIR-IICT, Hyderabad) and Dr. DS Reddy (Director, CSIR-IIIM, Jammu), the two partner institutes from CSIR said that they were looking forward to the outcome of this Phase II clinical efficacy trial on Colchicine, which may lead to life-saving intervention in the management of hospitalised patients.
Dr S Chandrasekhar (Director CSIR-IICT, Hyderabad)
Dr. DS Reddy (Director, CSIR-IIIM, Jammu)
India is one of the largest producers of this key drug and if successful, it will be made available to the patients at an affordable cost.
According to Ram Upadhayay, CEO, Laxai the enrollment of patients has already begun at multiple sites across India and the trial is likely to be completed in the next 8-10 weeks.
The drug can be made available to the large population of India based on the results of this trial and regulatory approval, he added.
Recent clinical studies have reported in leading medical journals about colchicine being associated with a significant reduction in the rates of recurrent pericarditis, post-pericardiotomy syndrome, and peri-procedural atrial fibrillation following cardiac surgery and atrial fibrillation ablation, according to a release.
Ram Upadhayaya, PhD
Chief Executive Officer, LAXAI
Ram Upadhayaya, CEO of Laxai Life Sciences, brings with him more than two decades of R&D experience spanning both academia and industry. A Ph. D in synthetic organic Chemistry, Ram has held key positions with leading international drug discovery organizations such as Bioimics AB Sweden, and Lupin India. Apart from his industrial background, Ram has been deeply associated with academic research. He was associated with Institute of Molecular Medicine, India as Principal Scientist as well as Uppsala University, Sweden in the capacity of Assistant Professor (Forskare). During these stints he significantly contributed to the development of novel therapeutics against infectious diseases such as AIDS and TB.
Ram has 10 international patents to his credit and has authored 25 peer reviewed publications. He is concurrently a consultant to the scientific advisory committee of the Principal Scientific Advisor, Government of India.
Raghava Reddy Kethiri, PhD, LAXAI
Chief Scientific Officer
25+ years of experience at various leadership positions in Biotech, CRO and Universities; Ex Karlsruhe Institute of Technology (KIT), Technical University of Dresden (TUD), JADO Technologies , Dresden, Germany, Jubilant Biosys, India
Delivered several leads, optimised leads and PCCs/DCs across Oncology, Pain, CNS, MD and Antibacterial therapeutics areas for global pharmaceutical companies. Co-Inventor of two clinical candidates ASN-001 ( NCT 02349139) for Metastatic Castration Resistant Prostrate Cancer & ASN-007 (NCT 03415126) for metastatic KRAS, NRAS & HRAS mutated solid tumors. Co-authored over 60 publications/patents (US/EU/Indian)
CAS Registry Number: 64-86-8
CAS Name:N-[(7S)-5,6,7,9-Tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo[a]heptalen-7-yl]acetamideMolecular Formula: C22H25NO6Molecular Weight: 399.44Percent Composition: C 66.15%, H 6.31%, N 3.51%, O 24.03%
Literature References: A major alkaloid of Colchicum autumnale L., Liliaceae. Extraction procedure: Chemnitius, J. Prakt. Chem. [II] 118, 29 (1928); F. E. Hamerslag, Technology and Chemistry of Alkaloids (New York, 1950) pp 66-80. Structure: Dewar, Nature155, 141 (1945); King et al.,Acta Crystallogr.5, 437 (1952); Horowitz, Ullyot, J. Am. Chem. Soc.74, 487 (1952). Crystal structure: L. Lessinger, T. N. Margulis, Acta Crystallogr.B34, 578 (1978).
Total synthesis: Schreiber et al.,Helv. Chim. Acta44, 540 (1961); Van Tamelen et al.,Tetrahedron14, 8 (1961); Nakamura, Chem. Pharm. Bull.8, 843 (1960); Sunagawa et al.,ibid.9, 81 (1961); 10, 281 (1962); Scott et al.,Tetrahedron21, 3605 (1965); Woodward, Harvey Lectures, Ser. 59 (Academic Press, New York, 1965) p 31; Kotani et al.,Chem. Commun.1974, 300; D. A. Evans et al.,J. Am. Chem. Soc.103, 5813 (1981).
Biosynthesis: Leete, Tetrahedron Lett.1965, 333; Battersby et al.,J. Chem. Soc.1964, 4257; Hill, Unrau, Can. J. Chem.43, 709 (1965). Tubulin-binding activity: J. M. Andreu, S. N. Timasheff, Proc. Natl. Acad. Sci. USA79, 6753 (1982). Toxicity: S. J. Rosenbloom, F. C. Ferguson, Toxicol. Appl. Pharmacol.13, 50 (1968); R. P. Beliles, ibid.23, 537 (1972). Clinical evaluations in cirrhosis of the liver: M. M. Kaplan et al.,N. Engl. J. Med.315, 1448 (1986); D. Kershenobich et al.,ibid.318, 1709 (1988). Bibliography of early literature: Eigsti, Lloydia10, 65 (1947).
Monograph: O. J. Eigsti, P. Dustin, Jr., Colchicine in Agriculture, Medicine, Biology and Chemistry (Iowa State College Press, Ames, Iowa, 1955). Reviews: Fleming, Selected Organic Syntheses (John Wiley, London, 1973) pp 183-207; G. Lagrue et al.,Ann. Med. Interne132, 496-500 (1981); F. D. Malkinson, Arch. Dermatol.118, 453-457 (1982). Comprehensive description: D. K. Wyatt et al.,Anal. Profiles Drug Subs.10, 139-182 (1981).
Properties: Pale yellow scales or powder, mp 142-150°. Darkens on exposure to light. Has been crystallized from ethyl acetate, pale yellow needles, mp 157°. [a]D17 -429° (c = 1.72). [a]D17 -121° (c = 0.9 in chloroform). pK at 20°: 12.35; pH of 0.5% soln: 5.9. uv max (95% ethanol): 350.5, 243 nm (log e 4.22; 4.47). One gram dissolves in 22 ml water, 220 ml ether, 100 ml benzene; freely sol in alcohol or chloroform. Practically insol in petr ether. Forms two cryst compds with chloroform, B.CHCl3 or B.2CHCl3, which do not give up their chloroform unless heated between 60 and 70° for considerable time. LD50 in rats (mg/kg): 1.6 i.v. (Rosenbloom, Ferguson); in mice (mg/kg): 4.13 i.v. (Beliles).
Melting point: mp 142-150°; mp 157°pKa: pK at 20°: 12.35; pH of 0.5% soln: 5.9Optical Rotation: [a]D17 -429° (c = 1.72); [a]D17 -121° (c = 0.9 in chloroform)Absorption maximum: uv max (95% ethanol): 350.5, 243 nm (log e 4.22; 4.47)
Toxicity data: LD50 in rats (mg/kg): 1.6 i.v. (Rosenbloom, Ferguson); in mice (mg/kg): 4.13 i.v. (Beliles)Use: In research in plant genetics (for doubling chromosomes).Therap-Cat: Gout suppressant. Treatment of Familial Mediterranean Fever.Therap-Cat-Vet: Has been used as an antineoplastic.Keywords: Antigout.
DOI: 10.1002/hlca.19610440225 DOI: 10.1021/ja00409a032
Here, we describe a concise, enantioselective, and scalable synthesis of (−)-colchicine (9.2% overall yield, >99% ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of colchicinoids was efficiently introduced using an intramolecular oxidopyrylium-mediated [5 + 2] cycloaddition reaction. Notably, the synthesized colchicinoid 23 exhibited potent inhibitory activity toward the cell growth of human cancer cell lines (IC50 = ∼3.0 nM), and greater inhibitory activity towards microtubule assembly than colchicine, making it a promising lead in the search for novel anticancer agents.
Enantioselective total synthesis of (−)- and (+)-colchicine
The synthesis began with the transition-metal-catalyzed C–H bond functionalization of 7 with 14 (Scheme 1). Inspired by Li’s seminal work,18 we applied the strategy to compound 7. Pleasingly, after optimization, we successfully generated the N-sulfonyl imine in situ by reaction of 7 with TsNH2 (15) in the presence of anhydrous CuSO4 in THF. Furthermore, subsequent treatment of this imine with [RhCp*Cl2]2 (1 mol%), AgSbF6 (4 mol%), NaOAc (2.0 equiv.), and 14 (2.0 equiv.) at 80 °C afforded ortho-olefinated benzaldehyde 16 in good yield (90% on a 0.5 g scale; 70% on a 5.0 g scale). This modified catalytic C–H bond activation involved a transient directing group.19
Recently one of my relatives have fallen ill and was prescribed with some colchicine. Looking at the structure of the molecule, and with nothing much to do, I decided to put my retrosynthetic skills to the test. Here is a picture of my thought process:
Is there a better way to design a synthesis for this compound using the disconnection method.
From 11b, a Birch reduction is carried out to give the qunione 10b. A rearrangement of the ketone with methanediazonium gives 9b. A dihydroxylation with a peroxy acid and subsequent addition of water gives 8b. A double dehydration reaction with sulfuric acid, coupled with the protection of the ketone with propan-1,3-diol gives the seven-membered quinone 7b. A Heck reaction (or Ullmann reaction) with 7a with a palladium catalyst yields 6. (The protection group is thereafter labelled “PG”) Friedel-Crafts acylation with ethanoyl chloride yields 5 (although on second thoughts, I should have done the acylation from 7a from the start). A Michael addition is then carried out with BuLiBuLi to lithiate the ketone to give the terminal imine 4. Since this terminal imine is unstable, a mild reducing agent converts the imine to the amine 3. The ketone is then removed by addition of dithiol and subsequently reduced by Raney nickel to form 2. Finally, a simple condensation reaction between the amine and acetic anhydride, followed by deprotection of the ketone using an acid, yields the final product colchicine, 1.
Colchicine is a medication used to treat gout and Behçet’s disease. In gout, it is less preferred to NSAIDs or steroids. Other uses for colchicine include the management of pericarditis and familial Mediterranean fever. Colchicine is taken by mouth.
Colchicine has a narrow therapeutic index and overdosing is therefore a significant risk. Common side effects of colchicine include gastrointestinal upset, particularly at high doses. Severe side effects may include low blood cells and rhabdomyolysis, and the medication can be deadly in overdose. It is not clear whether colchicine is safe for use during pregnancy, but its use during breastfeeding appears to be safe. Colchicine works by decreasing inflammation via multiple mechanisms.
Colchicine, in the form of the autumn crocus (Colchicum autumnale), has been used as early as 1500 BC to treat joint swelling. It was approved for medical use in the United States in 1961. It is available as a generic medication in the United Kingdom. In 2017, it was the 201st-most commonly prescribed medication in the United States, with more than two million prescriptions.
Colchicine is an alternative for those unable to tolerate NSAIDs in gout. At high doses, side effects (primarily gastrointestinal upset) limit its use. At lower doses, it is well tolerated. One review found low-quality evidence that low-dose colchicine (1.8 mg in one hour or 1.2 mg per day) reduced gout symptoms and pain, whereas high-dose colchicine (4.8 mg over 6 hours) was effective against pain, but caused more severe side effects, such as diarrhea, nausea or vomiting.
For treating gout symptoms, colchicine is used orally with or without food, as symptoms first appear. Subsequent doses may be needed if symptoms worsen. There is preliminary evidence that daily colchicine (0.6 mg twice daily) was effective as a long-term prophylaxis when used with allopurinol to reduce the risk of increased uric acid levels and acute gout flares, although adverse gastrointestinal effects may occur.
Colchicine is also used as an anti-inflammatory agent for long-term treatment of Behçet’s disease. It appears to have limited effect in relapsing polychondritis, as it may only be useful for the treatment of chondritis and mild skin symptoms. It is a component of therapy for several other conditions, including pericarditis, pulmonary fibrosis, biliary cirrhosis, various vasculitides, pseudogout, spondyloarthropathies, calcinosis, scleroderma, and amyloidosis. Research regarding the efficacy of colchicine in many of these diseases has not been performed. It is also used in the treatment of familial Mediterranean fever, in which it reduces attacks and the long-term risk of amyloidosis.
Colchicine is effective for prevention of atrial fibrillation after cardiac surgery. Potential applications for the anti-inflammatory effect of colchicine have been studied with regard to atherosclerosis and chronic coronary disease (e.g., stable ischemic heart disease). In people with recent myocardial infarction (recent heart attack), it has been found to reduce risk of future cardiovascular events. Its clinical use may grow to include this indication.
Long-term (prophylactic) regimens of oral colchicine are absolutely contraindicated in people with advanced kidney failure (including those on dialysis). About 10-20 percent of a colchicine dose is excreted unchanged by the kidneys; it is not removed by hemodialysis. Cumulative toxicity is a high probability in this clinical setting, and a severe neuromyopathy may result. The presentation includes a progressive onset of proximal weakness, elevated creatine kinase, and sensorimotor polyneuropathy. Colchicine toxicity can be potentiated by the concomitant use of cholesterol-lowering drugs.
Deaths – both accidental and intentional – have resulted from overdose of colchicine. Typical side effects of moderate doses may include gastrointestinal upset, diarrhea, and neutropenia. High doses can also damage bone marrow, lead to anemia, and cause hair loss. All of these side effects can result from inhibition of mitosis, which may include neuromuscular toxicity and rhabdomyolysis.
According to one review, colchicine poisoning by overdose (range of acute doses of 7 to 26 mg) begins with a gastrointestinal phase occurring 10–24 hours after ingestion, followed by multiple organ dysfunction occurring 24 hours to 7 days after ingestion, after which the affected person either declines into multi-organ failure or recovers over several weeks.
Colchicine can be toxic when ingested, inhaled, or absorbed in the eyes. Colchicine can cause a temporary clouding of the cornea and be absorbed into the body, causing systemic toxicity. Symptoms of colchicine overdose start 2 to 24 hours after the toxic dose has been ingested and include burning in the mouth and throat, fever, vomiting, diarrhea, and abdominal pain. This can cause hypovolemic shock due to extreme vascular damage and fluid loss through the gastrointestinal tract, which can be fatal.
If the affected person survives the gastrointestinal phase of toxicity, they may experience multiple organ failure and critical illness. This includes kidney damage, which causes low urine output and bloody urine; low white blood cell counts that can last for several days; anemia; muscular weakness; liver failure; hepatomegaly; bone marrow suppression; thrombocytopenia; and ascending paralysis leading to potentially fatal respiratory failure. Neurologic symptoms are also evident, including seizures, confusion, and delirium; children may experience hallucinations. Recovery may begin within six to eight days and begins with rebound leukocytosis and alopecia as organ functions return to normal.
Long-term exposure to colchicine can lead to toxicity, particularly of the bone marrow, kidney, and nerves. Effects of long-term colchicine toxicity include agranulocytosis, thrombocytopenia, low white blood cell counts, aplastic anemia, alopecia, rash, purpura, vesicular dermatitis, kidney damage, anuria, peripheral neuropathy, and myopathy.
No specific antidote for colchicine is known, but supportive care is used in cases of overdose. In the immediate period after an overdose, monitoring for gastrointestinal symptoms, cardiac dysrhythmias, and respiratory depression is appropriate, and may require gastrointestinal decontamination with activated charcoal or gastric lavage.
Mechanism of toxicity
With overdoses, colchicine becomes toxic as an extension of its cellular mechanism of action via binding to tubulin. Cells so affected undergo impaired protein assembly with reduced endocytosis, exocytosis, cellular motility, and interrupted function of heart cells, culminating in multi-organ failure.
In the United States, there are several hundred recorded cases of colchicine toxicity annually; approximately 10% of which end with serious morbidity or mortality. Many of these cases are intentional overdoses, but others were accidental; for example, if the drug was not dosed appropriately for kidney function. Most cases of colchicine toxicity occur in adults. Many of these adverse events resulted from the use of intravenous colchicine.
Colchicine interacts with the P-glycoprotein transporter, and the CYP3A4 enzyme involved in drug and toxin metabolism. Fatal drug interactions have occurred when colchicine was taken with other drugs that inhibit P-glycoprotein and CYP3A4, such as erythromycin or clarithromycin.
People taking macrolide antibiotics, ketoconazole or cyclosporine, or those who have liver or kidney disease, should not take colchicine, as these drugs and conditions may interfere with colchicine metabolism and raise its blood levels, potentially increasing its toxicity abruptly. Symptoms of toxicity include gastrointestinal upset, fever, muscle pain, low blood cell counts, and organ failure. People with HIV/AIDS taking atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, or saquinavir may experience colchicine toxicity. Grapefruit juice and statins can also increase colchicine concentrations.
In gout, inflammation in joints results from the precipitation of circulating uric acid, exceeding its solubility in blood and depositing as crystals of monosodium urate in and around synovial fluid and soft tissues of joints. These crystal deposits cause inflammatory arthritis, which is initiated and sustained by mechanisms involving various proinflammatory mediators, such as cytokines. Colchicine accumulates in white blood cells and affects them in a variety of ways: decreasing motility, mobilization (especially chemotaxis) and adhesion.
Under preliminary research are various mechanisms by which colchicine may interfere with gout inflammation:
- inhibits microtubule polymerization by binding to its constitutive protein, tubulin
- as availability of tubulin is essential to mitosis, colchicine may inhibit mitosis
- inhibits activation and migration of neutrophils to sites of inflammation
- interferes with the inflammasome complex found in neutrophils and monocytes that mediate interleukin-1β activation, a component of inflammation
- inhibits superoxide anion production in response to urate crystals
- interrupts mast cell and lysosome degranulation
- inhibits release of glycoproteins that promote chemotaxis from synovial cells and neutrophils
Generally, colchicine appears to inhibit multiple proinflammatory mechanisms, while enabling increased levels of anti-inflammatory mediators. Apart from inhibiting mitosis, colchicine inhibits neutrophil motility and activity, leading to a net anti-inflammatory effect, which has efficacy for inhibiting or preventing gout inflammation.
The plant source of colchicine, the autumn crocus (Colchicum autumnale), was described for treatment of rheumatism and swelling in the Ebers Papyrus (circa 1500 BC), an Egyptian medical papyrus. It is a toxic alkaloid and secondary metabolite. Colchicum extract was first described as a treatment for gout in De Materia Medica by Pedanius Dioscorides, in the first century AD. Use of the bulb-like corms of Colchicum to treat gout probably dates to around 550 AD, as the “hermodactyl” recommended by Alexander of Tralles. Colchicum corms were used by the Persian physician Avicenna, and were recommended by Ambroise Paré in the 16th century, and appeared in the London Pharmacopoeia of 1618. Colchicum use waned over time, likely due to the severe gastrointestinal side effects preparations caused. In 1763, Colchicum was recorded as a remedy for dropsy (now called edema) among other illnesses. Colchicum plants were brought to North America by Benjamin Franklin, who had gout himself and had written humorous doggerel about the disease during his stint as United States Ambassador to France.
Colchicine was first isolated in 1820 by the French chemists P. S. Pelletier and J. B.Caventou. In 1833, P. L. Geiger purified an active ingredient, which he named colchicine. It quickly became a popular remedy for gout. The determination of colchicine’s structure required decades, although in 1945, Michael Dewar made an important contribution when he suggested that, among the molecule’s three rings, two were seven-member rings. Its pain-relieving and anti-inflammatory effects for gout were linked to its ability to bind with tubulin.
An unintended consequence of the 2006 U.S. Food and Drug Administration (FDA) safety program called the Unapproved Drugs Initiative—through which the FDA sought more rigorous testing of efficacy and safety of colchicine and other unapproved drugs—was a price increase of 2000 percent  for “a gout remedy so old that the ancient Greeks knew about its effects.” Under Unapproved Drugs Initiative small companies like URL Pharma, a Philadelphia drugmaker, were rewarded with licenses for testing of medicines like colchicine. In 2009, the FDA reviewed a New Drug Application for colchicine submitted by URL Pharma. URL Pharma did the testing, gained FDA formal approval, and was granted rights over colchicine. With this monopoly pricing power, the price of colchicine increased.
In 2012 Asia’s biggest drugmaker, Takeda Pharmaceutical Co., acquired URL Pharma for $800 million including the rights to colchicine (brand name Colcrys) earning $1.2 billion in revenue by raising the price even more.
Oral colchicine had been used for many years as an unapproved drug with no FDA-approved prescribing information, dosage recommendations, or drug interaction warnings. On July 30, 2009, the FDA approved colchicine as a monotherapy for the treatment of three different indications (familial Mediterranean fever, acute gout flares, and for the prophylaxis of gout flares), and gave URL Pharma a three-year marketing exclusivity agreement in exchange for URL Pharma doing 17 new studies and investing $100 million into the product, of which $45 million went to the FDA for the application fee. URL Pharma raised the price from $0.09 per tablet to $4.85, and the FDA removed the older unapproved colchicine from the market in October 2010, both in oral and intravenous forms, but allowed pharmacies to buy up the older unapproved colchicine. Colchicine in combination with probenecid has been FDA-approved before 1982.
July 29, 2009, colchicine won FDA approval in the United States as a stand-alone drug for the treatment of acute flares of gout and familial Mediterranean fever. It had previously been approved as an ingredient in an FDA-approved combination product for gout. The approval was based on a study in which two doses (1.2 mg and 0.6 mg) an hour apart were as effective as higher doses in combating the acute flare of gout.
As a drug antedating the FDA, colchicine was sold in the United States for many years without having been reviewed by the FDA for safety and efficacy. The FDA reviewed approved colchicine for gout flares, awarding Colcrys a three-year term of market exclusivity, prohibiting generic sales, and increasing the price of the drug from $0.09 to $4.85 per tablet.
Numerous consensus guidelines, and previous randomized controlled trials, had concluded that colchicine is effective for acute flares of gouty arthritis. However, as of 2006, the drug was not formally approved by the FDA, owing to the lack of a conclusive randomized control trial (RCT). Through the Unapproved Drugs Initiative, the FDA sought more rigorous testing of the efficacy and safety of colchicine and other unapproved drugs. In exchange for paying for the costly testing, the FDA gave URL Pharma three years of market exclusivity for its Colcrys brand, under the Hatch-Waxman Act, based in part on URL-funded research in 2007, including pharmacokinetic studies and a randomized control trial with 185 patients with acute gout.
In April 2010, an editorial in the New England Journal of Medicine said that the rewards of this legislation are not calibrated to the quality or value of the information produced, that no evidence of meaningful improvement to public health was seen, and that it would be less expensive for the FDA, the National Institutes of Health or large insurers to pay for trials themselves. Furthermore, the cost burden of this subsidy falls primarily on patients or their insurers. In September 2010, the FDA ordered a halt to marketing unapproved single-ingredient oral colchicine.
Colchicine patents expire on February 10, 2029.
URL Pharma also received seven years of market exclusivity for Colcrys in the treatment of familial Mediterranean fever, under the Orphan Drug Law. URL Pharma then raised the price per tablet from $0.09 to $4.85 and sued to remove other versions from the market, increasing annual costs for the drug to U.S. state Medicaid programs from $1 million to $50 million. Medicare also paid significantly higher costs, making this a direct money-loser for the government. (In a similar case, thalidomide was approved in 1998 as an orphan drug for leprosy and in 2006 for multiple myeloma.)
It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002) and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.
Formulations and dosing
Trade names for colchicine are Colcrys or Mitigare which are manufactured as a dark– and light-blue capsule having a dose of 0.6 mg. Colchicine is also prepared as a white, yellow, or purple pill (tablet) having a dose of 0.6 mg.
Colchicine is typically prescribed to mitigate or prevent the onset of gout, or its continuing symptoms and pain, using a low-dose prescription of 0.6 to 1.2 mg per day, or a high-dose amount of up to 4.8 mg in the first 6 hours of a gout episode. With an oral dose of 0.6 mg, peak blood levels occur within one to two hours. For treating gout, the initial effects of colchicine occur in a window of 12 to 24 hours, with a peak within 48 to 72 hours. It has a narrow therapeutic window, requiring monitoring of the subject for potential toxicity. Colchicine is not a general pain relief drug, and is not used to treat pain in other disorders.
According to laboratory research, the biosynthesis of colchicine involves the amino acids phenylalanine and tyrosine as precursors. Giving radioactive phenylalanine-2-14C to C. byzantinum, another plant of the family Colchicaceae, resulted in its incorporation into colchicine. However, the tropolone ring of colchicine resulted from the expansion of the tyrosine ring. Radioactive feeding experiments of C. autumnale revealed that colchicine can be synthesized biosynthetically from (S)-autumnaline. That biosynthesic pathway occurs primarily through a phenolic coupling reaction involving the intermediate isoandrocymbine. The resulting molecule undergoes O-methylation directed by S-adenosylmethionine. Two oxidation steps followed by the cleavage of the cyclopropane ring leads to the formation of the tropolone ring contained by N-formyldemecolcine. N-formyldemecolcine hydrolyzes then to generate the molecule demecolcine, which also goes through an oxidative demethylation that generates deacetylcolchicine. The molecule of colchicine appears finally after addition of acetyl-coenzyme A to deacetylcolchicine.
Colchicine may be purified from Colchicum autumnale (autumn crocus) or Gloriosa superba (glory lily). Concentrations of colchicine in C. autumnale peak in the summer, and range from 0.1% in the flower to 0.8% in the bulb and seeds.
Colchicine is widely used in plant breeding by inducing polyploidy in plant cells to produce new or improved varieties, strains and cultivars. When used to induce polyploidy in plants, colchicine cream is usually applied to a growth point of the plant, such as an apical tip, shoot, or sucker. Seeds can be presoaked in a colchicine solution before planting. Since chromosome segregation is driven by microtubules, colchicine alters cellular division by inhibiting chromosome segregation during meiosis; half the resulting gametes, therefore, contain no chromosomes, while the other half contains double the usual number of chromosomes (i.e., diploid instead of haploid, as gametes usually are), and lead to embryos with double the usual number of chromosomes (i.e., tetraploid instead of diploid). While this would be fatal in most higher animal cells, in plant cells it is not only usually well-tolerated, but also frequently results in larger, hardier, faster-growing, and in general more desirable plants than the normally diploid parents. For this reason, this type of genetic manipulation is frequently used in breeding plants commercially.
When such a tetraploid plant is crossed with a diploid plant, the triploid offspring are usually sterile (unable to produce fertile seeds or spores), although many triploids can be propagated vegetatively. Growers of annual triploid plants not readily propagated vegetatively cannot produce a second-generation crop from the seeds (if any) of the triploid crop and need to buy triploid seed from a supplier each year. Many sterile triploid plants, including some trees, and shrubs, are becoming increasingly valued in horticulture and landscaping because they do not become invasive species and will not drop undesirable fruit and seed litter. In certain species, colchicine-induced triploidy has been used to create “seedless” fruit, such as seedless watermelons (Citrullus lanatus). Since most triploids do not produce pollen themselves, such plants usually require cross-pollination with a diploid parent to induce seedless fruit production.
The ability of colchicine to induce polyploidy can be also exploited to render infertile hybrids fertile, for example in breeding triticale (× Triticosecale) from wheat (Triticum spp.) and rye (Secale cereale). Wheat is typically tetraploid and rye diploid, with their triploid hybrid infertile; treatment of triploid triticale with colchicine gives fertile hexaploid triticale.
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- EXT LINKS
- “Colchicine”. Drug Information Portal. U.S. National Library of Medicine.
- “Colchicine : Biotoxin”. Emergency Response Safety and Health Database. 8 November 2017.
|Trade names||Colcrys, Mitigare, others|
|License data||US DailyMed: Colchicine|
|ATC code||M04AC01 (WHO)|
|Legal status||AU: S4 (Prescription only)CA: ℞-onlyUK: POM (Prescription only)US: ℞-only|
|Metabolism||Metabolism, partly by CYP3A4|
|Elimination half-life||26.6-31.2 hours|
|CompTox Dashboard (EPA)||DTXSID5024845 DTXSID20274387, DTXSID5024845|
|Chemical and physical data|
|Molar mass||399.437 g·mol−1|
|3D model (JSmol)||Interactive image|
///////////Colchicine, CSIR, Laxai Life Sciences, DCGI, clinical trials, Covid patients, covid 19, corona virus
NEW DRUG APPROVALS
BioE COVID-19, BECOV2D
Adjuvanted protein subunit vaccine
Corbevax is a “recombinant protein sub-unit” vaccine, which means it is made up of a specific part of SARS-CoV-2 — the spike protein on the virus’s surface.
The spike protein allows the virus to enter the cells in the body so that it can replicate and cause disease. However, when this protein alone is given to the body, it is not expected to be harmful as the rest of the virus is absent. The body is expected to develop an immune response against the injected spike protein. Therefore, when the real virus attempts to infect the body, it will already have an immune response ready that will make it unlikely for the person to fall severely ill.
Although this technology has been used for decades to make hepatitis B vaccines, Corbevax will be among the first Covid-19 vaccines to use this platform. Novavax has also developed a protein-based vaccine, which is still waiting for emergency use authorisation from various regulators.
How Corbevax was made
While it is indigenously produced, Corbevax’s beginnings can be traced to the Baylor College of Medicine’s National School of Tropical Medicine. The School had been working on recombinant protein vaccines for coronaviruses SARS and MERS for a decade.
“We knew all the techniques required to produce a recombinant protein (vaccine) for coronaviruses at high levels of efficiency and integrity,” said Dr Peter Hotez, Professor and Dean at the School.
When the genetic sequence for SARS-CoV-2 was made available in February 2020, researchers at the School pulled out the sequence for the gene for the spike protein, and worked on cloning and engineering it. The gene was then put into yeast, so that it could manufacture and release copies of the protein. “It’s actually similar to the production of beer. Instead of releasing alcohol, in this case, the yeast is releasing the recombinant protein,” Dr Hotez said.
After this, the protein was purified to remove any remnants of the yeast “to make it pristine”. Then, the vaccine was formulated using an adjuvant to better stimulate the immune response.
Most of these ingredients are cheap and easy to find.
In August, BCM transferred its production cell bank for this vaccine to Biological E, so that the Hyderabad-based company could take the candidate through trials. The vaccine has received approval for phase 3 trials, which the government expects will be over by July.
Biological E is also expected to scale up production for the world.
How Corbevax is different
Other Covid-19 vaccines approved so far are either mRNA vaccines (Pfizer and Moderna), viral vector vaccines (AstraZeneca-Oxford/Covishield, Johnson & Johnson and Sputnik V) or inactivated vaccines (Covaxin, Sinovac-CoronaVac and Sinopharm’s SARS-CoV-2 Vaccine–Vero Cell).
Inactivated vaccines, which include killed particles of the whole SARS-CoV-2 virus, attempt to target the entire structure of the virus. On the other hand, Corbevax, like the mRNA and viral vector Covid-19 vaccines, targets only the spike protein, but in a different way.
Viral vector and mRNA and vaccines use a code to induce our cells to make the spike proteins against which the body have to build immunity. “In this case (Corbevax), we’re actually giving the protein,” said Dr Hotez.
Like most other Covid-19 vaccines, Corbevax is administered in two doses. However, as it is made using a low-cost platform, it is also expected to be among the cheapest available in the country.
Why Corbevax matters
This is the first time the Indian government has placed an order for a vaccine that has not received emergency use authorisation, paying Rs 1,500 crore in advance to block an order that could vaccinate 15 crore Indian citizens. The Centre has provided major pre-clinical and clinical trial support towards the vaccine’s development, including a grant-in-aid of Rs 100 crore from the Department of Biotechnology.
A major reason for India placing such a big order is the difficulties it is facing in enhancing vaccine supplies. While the US, UK and the EU had made advance payments and at-risk investments into vaccines like Pfizer, AstraZeneca and Moderna, India waited until after its first two vaccines were approved before placing limited orders. Even after the government eased regulatory requirements for foreign vaccines, it did not receive a speedy response from companies like Pfizer and Moderna, their supplies already blocked through orders from other countries. India is currently in negotiations for a limited supply of Pfizer’s vaccine, and expecting to secure up to two billion doses of Covid vaccines by December this year. Given the ease with which it can be mass produced, Corbevax could make up a sizeable portion of this expected supply.
Biological E, the manufacturer of Corbevax
Biological E, headquartered in Hyderabad, was founded by Dr D V K Raju in 1953 as a biological products company that pioneered the production of heparin in India. By 1962, it forayed into the vaccines space, producing DPT vaccines on a large-scale. Today, it is among the major vaccine makers in India and, by its own claim, the “largest” tetanus vaccine producer in the world.
It has seven WHO-prequalified shots, including a five-in-one vaccine against diphtheria, tetanus, pertussis, hepatitis B and haemophilus influenza type-b infections. Its vaccines are supplied to over 100 countries and it has supplied more than two billion doses in the last 10 years alone.
Since 2013, the company has been under the management of Mahima Datla — the third generation of the founding family. During her time as managing director, the company has received WHO prequalification of its Japanese encephalitis, DTwP and Td as well as measles and rubella vaccines and also commenced commercial operations in the US.
Corbevax or BioE COVID-19, is a COVID-19 vaccine candidate developed by Indian biopharmacutical firm Biological E. Limited (BioE), the Baylor College of Medicine in Houston, United States, and Dynavax Technologies. It is a protein subunit vaccine.
Phase I and II trials
Phase III trials
In April 2021, the Drugs Controller General of India permitted the vaccine candidate to start phase III clinical trials. A total of 1,268 healthy participants between the age of 18 and 80 years to be selected from 15 sites across India for the trial and intended to be part of a larger global Phase III study.
Manufacturing and Orders
In April 2021, the U.S. International Development Finance Corporation (DFC) announced that it would fund the expansion of BioE’s manufacturing capabilities, so that it could produce at least 1 billion doses by end of 2022.
- ^ Bharadwaj, Swati (3 June 2021). “Telangana: Biological E starts at risk manufacturing of Corbevax”. The Times of India. Retrieved 3 June 2021.
- ^ “A prospective open label randomised phase-I seamlessly followed by phase-II study to assess the safety, reactogenicity and immunogenicity of Biological E’s novel Covid-19 vaccine containing Receptor Binding Domain of SARS-CoV-2 for protection against Covid-19 disease when administered intramuscularly in a two dose schedule (0, 28D) to healthy volunteers”. ctri.nic.in. Clinical Trials Registry India. 13 January 2021. CTRI/2020/11/029032. Archived from the original on 12 November 2020.
- ^ “CEPI partners with Biological E Limited to advance development and manufacture of COVID-19 vaccine candidate”. cepi.net. CEPI. Retrieved 5 March 2021.
- ^ Chui M (16 November 2020). “Biological E. Limited and Baylor COVID-19 vaccine begins clinical trial in India”. Baylor College of Medicine.
- ^ Jump up to:a b Leo L (16 November 2020). “Biological E initiates human trials of vaccine”. Mint.
- ^ “Coronavirus | Biological E gets nod to start Phase III trials of COVID-19 vaccine”. The Hindu. 24 April 2021.
- ^ Jump up to:a b Leo, Leroy (24 April 2021). “Biological E completes phase-2 covid vaccine trial, gets SEC nod for phase-3”. mint.
- ^ “A Prospective, multicentre, Phase II Seamlessly Followed by Phase III Clinical Study to Evaluate the Immunogenicity and Safety of Biological E’s CORBEVAX Vaccine for Protection Against COVID-19 Disease When Administered to COVID-19-Negative Adult Subjects”. ctri.nic.in. Clinical Trials Registry India. 5 June 2021. CTRI/2021/06/034014.
- ^ Basu, Nayanima (25 April 2021). “US assures export of raw materials to India for Covid vaccines as Doval speaks to Sullivan”. ThePrint.
- ^ “Health ministry buys 300 mn doses of Biological-E’s Covid vaccine in advance”. Hindustan Times. 3 June 2021. Retrieved 4 June 2021.
CorbevaxVaccine descriptionTargetSARS-CoV-2Vaccine typeProtein subunitClinical dataTrade namesCorbevaxOther namesBECOV2DRoutes of
- “Explained: How Corbevax is different”. The Indian Express.
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///////////Biological E, SARS-CoV-2, Baylor College, CORONA VIRUS, COVID 19, Corbevax, BioE COVID-19, BECOV2D, INDIA, Dynavax Technologies
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