CoVLP

CoVLP

Vaccine description
Target	SARS-CoV-2
Vaccine type	Virus-like particles
Clinical data
Trade names	Covifenz
Routes of administration	Intramuscular
Legal status
Legal status	CA: ℞-only [1] [2] [3] [4] [5]
Identifiers
DrugBank	DB15852

CoVLP (brand name Covifenz) was a COVID-19 vaccine developed by Medicago in Canada and GlaxoSmithKline (GSK). The product and Medicago, Inc. were owned by Mitsubishi who terminated the company and program in February 2023 due to high international market competition for COVID-19 vaccines. ^[6]

It is a coronavirus virus-like particle vaccine grown in the Australian weed, Nicotiana benthamiana . ^{[7] [8] [9] [10]}

The Medicago method to manufacture CoVLP was a "molecular farming" technology regarded as rapid, low-cost, and safe. ^{[8] [11]} It was proposed specifically for production of COVID-19 vaccines. ^{[12] [13]}

In February 2022, Health Canada authorized use of CoVLP for preventing COVID-19 infection in adults 18 to 64 years old. ^[3] The authorization stated there was an efficacy rate of 71% after two vaccinations against symptoms of COVID-19 disease and 100% efficacy against severe COVID-19 infections. ^[3]

Efficacy

On 7 December 2021, Medicago-GSK announced a preliminary analysis showing an overall efficacy of 71%, with 75% against the Delta variant and 89% efficacy against Gamma. ^[14]

Pharmacology

CoVLP is an example of a virus-like particle vaccine, consisting of a molecular complex which closely resembles a virus, but is non-infectious because it contains no viral genetic material. ^[8] It uses recombinant spike proteins derived from SARS-CoV-2. ^{[15] [16]}

Manufacturing

N. benthamiana plant used by Medicago as a "minifactory" for rapid production of coVLP

Nicotiana benthamiana, leaf

The virus-like particles are produced by creating a bacterium engineered with genes of the virus, then introducing the bacteria into Nicotiana benthamiana plants. ^[8] The plants take up the bacteria virus-derived genetic material, producing in its leaves the virus-like particles, which are then harvested and extracted. ^{[10] [17]}

In use since the 1990s, the method of using a plant like N. benthamiana has been called "molecular farming" or a "plant-based factory", having vaccine manufacturing advantages of rapid, low-cost production of proteins, large scalability for production, and safety of using plants for pharmaceutical production. ^{[8] [11]} It has been proposed specifically for production of COVID-19 vaccines. ^{[12] [13]}

History

Medicago started developing the COVID-19 vaccine candidate, CoVLP, in 2020, in collaboration with the governments of Canada and Quebec, using a plant-based vaccine technology with an adjuvant manufactured by GlaxoSmithKline (GSK). ^[15] The GSK adjuvant is intended to enhance the immune response to CoVLP, reducing the amount of antigen required per dose, thereby facilitating mass production of vaccine doses. ^{[18] [19]}

In March 2022, the vaccine was rejected by the World Health Organization due to the tobacco company Philip Morris International owning a stake in Medicago. ^[20] The UN agency has a strict policy about engagement with the tobacco industry. ^[21]

In February 2023, Mitsubishi announced the shuttering of Medicago, and with that, the withdrawal of Medicago products from the market, marking the end of coVLP/Covifenz. Mitsubishi had determined that the vaccine was no longer commercially viable, with the changing landscape of the global vaccine marketplace, and demand for the product. ^[6]

Society and culture

Legal status

In December 2021, Medicago announced submission of the Phase III results to Health Canada. ^[22]

In February 2022, Health Canada approved the use of CoVLP for adults aged 18–64 in Canada. ^[3] The CoVLP vaccine was sold under the brand name Covifenz. ^[23]

Research

Phase I

Beginning in August 2020, CoVLP was in a Phase I clinical trial at two locations in Quebec to evaluate its safety and immune response. ^[24] 180 Adults (18–55 years) were randomized at two sites in Quebec, Canada, to receive two intramuscular doses of CoVLP (3.75 μg, 7.5 μg, and 15 μg) 21 d apart, alone or adjuvanted with AS03 or CpG1018. All formulations were well tolerated, and adverse events after vaccination were generally mild to moderate, transient and highest in the adjuvanted groups. There was no CoVLP dose effect on serum NAbs, but titers increased significantly with both adjuvants. After the second dose, NAbs in the CoVLP + AS03 groups were more than tenfold higher than titers in Coronavirus 2019 convalescent sera. Both spike protein-specific interferon-γ and interleukin-4 cellular responses were also induced. This pre-specified interim analysis supports further evaluation of the CoVLP vaccine candidate. ^[25]

Phase II

In November 2020, Medicago-GSK started a Phase II clinical trial for CoVLP with 588 participants. Researchers reported day 42 interim safety 17 and immunogenicity data from a Phase II, randomized, placebo-controlled trial in Adults aged 18+ immunized with a virus-like particle vaccine candidate produced in plants displaying 19 SARS-CoV-2 spike glycoprotein (CoVLP) adjuvanted with AS03 (NCT04636697). This report focused on presenting safety, tolerability and immunogenicity, as measured by 21 neutralizing antibody (NAb) and cell mediated immunity (IFN-γ and IL-4 ELISpot) responses, 22 in Adults aged 18–64 (Adults) and Older Adults aged 65+ (Older Adults).^{[ citation needed ]}

Phase III

In April 2021, Medicago-GSK started a Phase III clinical trial for CoVLP, enrolling 30,918 participants in North America, Latin America, and Europe. ^[16] GSK and Medicago announced the success of the trial on December 7, 2021. ^[26] According to the analysis of the data presented by Health Canada's National Advisory Committee on Immunization (NACI), CoVLP exhibited 69.5% efficacy against laboratory-confirmed, symptomatic SARS-CoV-2 infection starting at least 7 days after the second dose of the vaccine in the intention-to-treat analysis, even though the trial included some participants who had previously been infected with the virus when the trial began. ^[27] Additionally, it exhibited 100.0% efficacy against the Alpha variant, 75.3% against the Delta variant, and 88.6% against the Gamma variant in the per-protocol analysis, with "similar" results in the intention-to-treat analysis. ^[27]

References

1. "Product monograph for Covifenz" (PDF). Medicago, Inc. 24 February 2022.
2. "Medicago Covifenz COVID-19 vaccine". Health Canada . 24 February 2022. Retrieved 29 May 2022.
3. "Health Canada authorizes Medicago COVID-19 vaccine for adults 18 to 64 years of age" (Press release). Health Canada. 24 February 2022. Retrieved 24 February 2022.
4. "Summary Basis of Decision (SBD) for Covifenz". Health Canada . 23 October 2014. Retrieved 29 May 2022.
5. "Covifenz (virus-like particles (VLP) of SARS-CoV-2 spike protein)". Health Canada . 24 February 2022. Retrieved 31 May 2022.
6. Lavery I, Boynton S (2 February 2023). "Medicago to cease operations in Quebec, scuttling COVID-19 vaccine production plans". Global News. Retrieved 2 February 2023.
7. 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.
8. LeBlanc Z, Waterhouse P, Bally J (December 2020). "Plant-Based Vaccines: The Way Ahead?". Viruses. 13 (1): 5. doi: 10.3390/v13010005 . PMC   7822169 . PMID   33375155.
9. St Philip E, Favaro A, MacLeod M (14 July 2020). "The hunt for a vaccine: Canadian company begins human testing of COVID-19 candidate". CTV News. Retrieved 14 July 2020.
10. Chander V (14 July 2020). "Canada's Medicago begins human trials of plant-based COVID-19 vaccine". National Post. Reuters. Retrieved 14 July 2020.
11. Fischer R, Buyel JF (2020). "Molecular farming - The slope of enlightenment". Biotechnology Advances. 40: 107519. doi:10.1016/j.biotechadv.2020.107519. PMID   31954848. S2CID   210830170.
12. Dhama K, Natesan S, Iqbal Yatoo M, Patel SK, Tiwari R, Saxena SK, Harapan H (December 2020). "Plant-based vaccines and antibodies to combat COVID-19: current status and prospects". Human Vaccines & Immunotherapeutics. 16 (12): 2913–2920. doi:10.1080/21645515.2020.1842034. PMC   7754927 . PMID   33270484.
13. Balfour H (15 April 2020). "Plant bio-factories contributing to the COVID-19 fight". Drug Target Review. Retrieved 30 January 2021.
14. "Medicago and GSK announce positive Phase 3 efficacy and safety results for adjuvanted plant-based COVID-19 vaccine candidate". Medicago. 7 December 2021. Retrieved 23 December 2021.
15. "GSK partners with Medicago to develop plant-based Covid-19 vaccine". Pharmaceutical Technology. 8 July 2020. Retrieved 3 August 2020.
16. "Medicago and GSK start of Phase II/III clinical trials of adjuvanted COVID-19 vaccine candidate". Drug Discovery World. 13 November 2020. Retrieved 29 November 2020.
17. "VLP technologies and production platform". Medicago. Retrieved 30 January 2021.
18. Chung JY, Thone MN, Kwon YJ (March 2021). "COVID-19 vaccines: The status and perspectives in delivery points of view". Advanced Drug Delivery Reviews. 170: 1–25. doi:10.1016/j.addr.2020.12.011. PMC   7759095 . PMID   33359141.
19. Lucy Parsons (8 July 2020). "GSK signs deal with Medicago for COVID-19 vaccine". PMLive. Retrieved 30 January 2021.
20. Ahmar Khan. "WHO rejects Medicago's COVID-19 vaccine due to ties to tobacco giant". Global News. Retrieved 16 July 2022.
21. "Feds won't buy tobacco company's stake in Medicago to free up COVID vaccines: minister". Global News. The Canadian Press. Retrieved 16 July 2022.
22. "Medicago submits Phase 3 data to Health Canada for its plant-based COVID-19 vaccine candidate". Medicago. 16 December 2021. Retrieved 23 December 2021.
23. "Medicago and GSK announce the approval by Health Canada of Covifenz, an Adjuvanted Plant-Based COVID-19 Vaccine" (Press release). Medicago. 24 February 2022. Retrieved 24 February 2022.
24. Clinical trial number NCT04450004 for "Safety, Tolerability and Immunogenicity of a Coronavirus-Like Particle COVID-19 Vaccine in Adults Aged 18-55 Years" at ClinicalTrials.gov
25. Ward BJ, Gobeil P, Séguin A, Atkins J, Boulay I, Charbonneau PY, et al. (June 2021). "Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19". Nature Medicine. 27 (6): 1071–1078. doi:10.1038/s41591-021-01370-1. PMC   8205852 . PMID   34007070.
26. "Medicago and GSK announce positive Phase 3 efficacy and safety results for adjuvanted plant-based COVID-19 vaccine candidate". GlaxoSmithKline. 7 December 2021.
27. "An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI) Recommendations on the use of Medicago COVID-19 vaccine (Covifenz)" (PDF). Health Canada. 11 March 2022. Retrieved 29 March 2022.