CoVLP

CoVLP
Vaccine description
TargetSARS-CoV-2
Vaccine typeVirus-like particles
Clinical data
Routes of
administration		Intramuscular
Identifiers
DrugBank

CoVLP is a COVID-19 vaccine candidate developed by Medicago and GlaxoSmithKline (GSK). It is a coronavirus virus-like particle vaccine grown in the Australian weed, Nicotiana benthamiana.[1][2][3]

The Medicago method to manufacture CoVLP is a "molecular farming" technology regarded as rapid, low-cost, and safe.[1][4] It has been proposed specifically for production of COVID-19 vaccines.[5][6]

As of September 2021, the Medicago CoVLP vaccine candidate was in a Phase II-III clinical trial in several countries in North America, Latin America and Europe, involving up to 30,918 participants.[7]

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.[8]

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 its contains no viral genetic material.[1] It uses recombinant spike proteins derived from SARS-CoV-2.[9][10]

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.[1] The plants take up the bacteria virus-derived generic material, producing in its leaves the virus-like particles, which are then harvested and extracted.[3][11]

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.[1][4] It has been proposed specifically for production of COVID-19 vaccines.[5][6]

History

Medicago is developing the COVID-19 vaccine candidate, CoVLP, in collaboration with the governments of Canada and Quebec, and by using an adjuvant manufactured by GlaxoSmithKline (GSK).[9] 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.[12][13]

Clinical trials

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.[14] 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.[15]

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 focuses 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). The Phase II trial has a primary completion date of December 2021 and the estimated completion date of April 2022.[7] After a successful Phase II, the scientists moved into a Phase III trial.

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.[7][16][10]

Authorization

On 16 December 2021 Medicago announced submission of the Phase III results to Health Canada.[17]

References

  1. 1 2 3 4 5 LeBlanc, Zacharie; Waterhouse, Peter; Bally, Julia (22 December 2020). "Plant-based vaccines: The way ahead?". Viruses. 13 (1): 5. doi:10.3390/v13010005. ISSN 1999-4915. PMC 7822169. PMID 33375155.
  2. ↑ 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.
  3. 1 2 Chander V (14 July 2020). "Canada's Medicago begins human trials of plant-based COVID-19 vaccine". National Post. Reuters. Retrieved 14 July 2020.
  4. 1 2 Fischer, Rainer; Buyel, Johannes F. (2020). "Molecular farming – The slope of enlightenment (Review)". Biotechnology Advances. 40: 107519. doi:10.1016/j.biotechadv.2020.107519. ISSN 0734-9750. PMID 31954848. S2CID 210830170.
  5. 1 2 Dhama, Kuldeep; Natesan, Senthilkumar; Iqbal Yatoo, Mohd.; Patel, Shailesh Kumar; Tiwari, Ruchi; Saxena, Shailendra K; Harapan, Harapan (1 December 2020). "Plant-based vaccines and antibodies to combat COVID-19: current status and prospects (Review)". Human Vaccines and Immunotherapeutics. 16 (12): 2913–2920. doi:10.1080/21645515.2020.1842034. ISSN 2164-5515. PMC 7754927. PMID 33270484.
  6. 1 2 Hannah Balfour (15 April 2020). "Plant bio-factories contributing to the COVID-19 fight". Drug Target Review. Retrieved 30 January 2021.
  7. 1 2 3 Clinical trial number NCT04636697 for "Study of a Recombinant Coronavirus-Like Particle COVID-19 Vaccine in Adults" at ClinicalTrials.gov
  8. ↑ "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.
  9. 1 2 "GSK partners with Medicago to develop plant-based Covid-19 vaccine". Pharmaceutical Technology. 8 July 2020. Retrieved 3 August 2020.
  10. 1 2 "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.
  11. ↑ "VLP technologies and production platform". Medicago. Retrieved 30 January 2021.
  12. ↑ Chung, Jee Young; Thone, Melissa N.; Kwon, Young Jik (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. ISSN 0169-409X. PMC 7759095. PMID 33359141.
  13. ↑ Lucy Parsons (8 July 2020). "GSK signs deal with Medicago for COVID-19 vaccine". PMLive. Retrieved 30 January 2021.
  14. ↑ 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
  15. ↑ Ward, Brian J.; Gobeil, Philipe; Séguin, Annie; Atkins, Judith; Boulay, Iohann; Charbonneau, Pierre-Yves; Couture, Manon; D’Aoust, Marc-André; Dhaliwall, Jiwanjeet; Finkle, Carolyn; Hager, Karen; Mahmood, Asif; Makarkov, Alexander; Cheng, Matthew P.; Pillet, Stéphane; Schimke, Patricia; St-Martin, Sylvie; Trépanier, Sonia; Landry, Nathalie (18 May 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. ISSN 1078-8956. PMC 8205852. PMID 34007070.
  16. ↑ "Medicago and GSK start Phase 3 trial of adjuvanted COVID-19 vaccine candidate". GlaxoSmithKline. 16 March 2021. Retrieved 13 April 2021.
  17. ↑ "Medicago submits Phase 3 data to Health Canada for its plant-based COVID-19 vaccine candidate". Medicago. 16 December 2021. Retrieved 23 December 2021.
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