MVC COVID-19 vaccine

MVC COVID-19 vaccine

Vaccine description
Target	SARS-CoV-2
Vaccine type	Protein subunit
Clinical data
Other names	MVC-COV1901
Routes of administration	Intramuscular
Legal status
Legal status	Full and emergency authorizations Full list of MVC vaccine authorizations
Identifiers
CAS Number	2565776-92-1
DrugBank	DB15854

The MVC COVID-19 vaccine (Chinese: 高端新冠肺炎疫苗; pinyin: Gāoduān xīnguàn fèiyán yìmiáo; Wade–Giles: Kaotuan hsinkuan feiyen imiao), 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 in Taiwan, American company Dynavax Technologies, and the U.S. National Institutes of Health.^[1][2]

Technology

This vaccine is made by the recombinant S-2P spike protein.^[3][4] It is adjuvanted with CpG 1018 supplied by Dynavax, which was used in a previously FDA-approved adult hepatitis B vaccine.^[3][5]

Clinical trials

On 16 February 2020, Medigen Vaccine Biologics Corporation (MVC) signed a collaboration agreement with US 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.^[6] On 23 July 2020, Medigen announced collaboration with Dynavax Technologies to develop COVID-19 vaccine.^[5][7]

On 13 October 2020, MVC 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.^[8][9]

On 25 January 2021, MVC initiated a Phase 2 Clinical Trial for its COVID-19 vaccine candidate MVC-COV1901 with the first participant being dosed.^[3][10] The multi-center, randomized, placebo-controlled trial included 3,844 participants aged 20 or older.^[11]

On 10 June 2021, MVC released its COVID-19 vaccine Phase 2 interim analysis results, and announced that it will request Emergency Use Authorization (EUA) with the concluding of the Phase 2 Clinical Trial.^[12]

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 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.^[13]

On 20 July 2021, MVC 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.^[14] The decision was controversial as immuno-bridging trials were not as widely accepted as disease endpoint trials. However, many countries have already started the discussion of whether to accept immuno-bridging as the endpoint and later adopted.^[15] The trail was successfully completed and received EUA from Paraguay on February 14, 2022.^[16]

On 26 October 2021, the World Health Organization (WHO) selected Medigen vaccine as one of its Solidarity Trial Vaccines. The trial is designed to rapidly evaluate the efficacy and safety of promising new candidate vaccines selected by an independent vaccine prioritization advisory group. ^[17]

Adolescents trial

In July 2021, Medigen commenced phase II trials for adolescents aged 12–18.^[18]

Authorization

Full authorization   Emergency authorization   Allowed for travel

See also: List of COVID-19 vaccine authorizations § Medigen

On 19 July 2021, MVC COVID-19 vaccine obtained Emergency Use Authorization (EUA) approval from the Taiwanese government after fulfilling EUA requirements set by Taiwanese authority.^[19] The EUA, however, was met with controversy due to the lack of efficacy data and Phase 3 Clinical Trial. The EUA was granted instead based on the immunobridging study in comparison with antibody found on people who received AstraZeneca vaccine. On August 23, 2021, President Tsai Ing-Wen was among the first Taiwanese to receive a dose of the vaccine.^[20]

Tsai Ing-Wen receiving a dose of the vaccine

Controversies

In May 2021, when Taiwan experienced an outbreak of domestic cases, the government announced that the vaccine would be available in July despite the result of the phase 2 trial was yet to be announced. In June 2021, the vaccine had just completed the second phase clinical trial, but the vaccine was sent to Taiwan FDA for the application of EUA.^[21] Seroconversion rate was used as the surrogate endpoint, though there was lack of evidence at that time. Compared to EUA of vaccine issued in the US, both Moderna and BNT/Pfizer vaccine finished interim analysis from Phase 3 study, which Medigen vaccine skipped.^[22]

The controversy arose because immunobridging was not widely accepted as sufficient for EUA at the time. However, due to difficulty to conduct traditional, placebo-controlled efficacy trials in some countries, as few candidates are available or willing to participate, there were discussions to focus on immunobridging studies as an acceptable approach for authorizing COVID-19 vaccines by the International Coalition of Medicines Regulatory Authorities (ICMRA). As the result of the workshop convened in 24 June 2021, immunobridging has now been accepted by the UK, Australia, Canada, Singapore, and Switzerland among other countries.^[15][23] US FDA also authorized Pfizer-BioNTech vaccine for children 5 to 11 years old based on immunobridging alone. ^[24][25]

References

1. "Dynavax and Medigen Announce Collaboration to Develop a Novel Adjuvanted COVID-19 Vaccine Candidate". GlobeNewswire. 23 July 2020. Retrieved 7 June 2021.
2. 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 (Taiwan)). Mirror Media.
3. "Medigen Vaccine Biologics COVID-19 Vaccine Adjuvanted with Dynavax's CpG 1018 Announces First Participant Dosed in Phase 2 Clinical Trial in Taiwan". www.medigenvac.com. Retrieved 7 August 2021.
4. Hotez PJ, Bottazzi ME (January 2022). "Whole Inactivated Virus and Protein-Based COVID-19 Vaccines". Annual Review of Medicine. 73 (1): 55–64. doi:10.1146/annurev-med-042420-113212. PMID 34637324. S2CID 238747462.
5. "Medigen Collaborates with Dynavax to Develop Novel Adjuvanted COVID-19 Vaccine Candidate". www.medigenvac.com. Retrieved 7 August 2021.
6. "MVC and NIH Collaborate to Develop COVID-19 Vaccine". www.medigenvac.com. Retrieved 7 August 2021.
7. "MVC Signed an License Agreement with NIH on COVID-19 Vaccine". Medigen. 5 May 2020. Retrieved 27 July 2021.
8. "Medigen's COVID-19 Vaccine Combined with Dynavax's CpG 1018 Adjuvant Receives Taiwan Government Subsidy with First Participant Dosed in Early October". www.medigenvac.com. Retrieved 7 August 2021.
9. "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.
10. "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.
11. Hsieh SM, Liu MC, Chen YH, Lee WS, Hwang SJ, Cheng SH, et al. (December 2021). "Safety and immunogenicity of CpG 1018 and aluminium hydroxide-adjuvanted SARS-CoV-2 S-2P protein vaccine MVC-COV1901: interim results of a large-scale, double-blind, randomised, placebo-controlled phase 2 trial in Taiwan". The Lancet. Respiratory Medicine. 9 (12): 1396–1406. doi:10.1016/S2213-2600(21)00402-1. PMC 8514195. PMID 34655522. S2CID 238748264.
12. "MVC Released COVID-19 Vaccine Phase 2 Interim Analysis Result". www.medigenvac.com. Retrieved 7 August 2021.
13. Hsieh SM, Liu WD, Huang YS, Lin YJ, Hsieh EF, Lian WC, et al. (August 2021). "Safety and immunogenicity of a Recombinant Stabilized Prefusion SARS-CoV-2 Spike Protein Vaccine (MVC-COV1901) Adjuvanted with CpG 1018 and Aluminum Hydroxide in healthy adults: A Phase 1, dose-escalation study". eClinicalMedicine. 38: 100989. doi:10.1016/j.eclinm.2021.100989. PMC 8233066. PMID 34222848.
14. "MVC Announces Paraguay Approval of IND Application for Phase 3 Clinical Trial". www.medigenvac.com. Retrieved 7 August 2021.
15. "Immuno-bridging studies are sufficient for authorising new COVID-19 vaccines, say regulators". European Pharmaceutical Review. Retrieved 14 January 2022.
16. "Medigen vaccine passes Paraguay trial, earns EUA". Taipei Times. 16 February 2022. Retrieved 23 June 2022.
17. "WHO Statement on Solidarity Trial Vaccines".
18. "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.
19. "MVC COVID-19 Vaccine Obtains Taiwan EUA Approval". www.medigenvac.com. Retrieved 7 August 2021.
20. Taiwan begins contested rollout of new Medigen domestic vaccine, Nikkei Asia, Erin Hale, August 23, 2021
21. 潘姿羽 (10 June 2021). "高端疫苗拚上市 解盲、二期臨床試驗一次看懂". www.cna.com.tw (in Chinese (Taiwan)). 中央社 CNA. Retrieved 15 June 2021.
22. 聯合新聞網 (18 June 2021). "缺三期試驗 國產疫苗EUA遭質疑 | 聯合新聞網：最懂你的新聞網站". 聯合新聞網 (in Chinese). Retrieved 12 September 2021.
23. "Access Consortium: Alignment with ICMRA consensus on immunobridging for authorising new COVID-19 vaccines".
24. "US FDA Signals New COVID-19 Vaccines Could Be Authorized With Just Immunogenicity Studies". 7 September 2021.
25. "FDA Review of Effectiveness and Safety of Pfizer-BioNTech COVID-19 Vaccine in Children 5 through 11 Years of Age Emergency Use Authorization Amendment". Food and Drug Administration.

External links