CoVLP

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

CoVLP (brand name Covifenz) is a COVID-19 vaccine 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]

In February 2022, Health Canada authorized use of CoVLP for preventing COVID-19 infection in adults 18 to 64 years old.[7] 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.[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 it 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 genetic 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 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).[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 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).

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.[10]

Authorization

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

On 24 February 2022, Health Canada approved the use of CoVLP for adults aged 18-64 in Canada.[7] The CoVLP vaccine will be marketed under the name Covifenz.[17]

References

  1. ^ a b c d e 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.
  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. ^ a b 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. ^ a b 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.
  5. ^ a b 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.
  6. ^ a b Balfour H (15 April 2020). "Plant bio-factories contributing to the COVID-19 fight". Drug Target Review. Retrieved 30 January 2021.
  7. ^ a b c "Health Canada authorizes Medicago COVID-19 vaccine for adults 18 to 64 years of age". Health Canada, Government of Canada. 24 February 2022. Retrieved 24 February 2022.
  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. ^ a b "GSK partners with Medicago to develop plant-based Covid-19 vaccine". Pharmaceutical Technology. 8 July 2020. Retrieved 3 August 2020.
  10. ^ a b "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 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.
  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 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.
  16. ^ "Medicago submits Phase 3 data to Health Canada for its plant-based COVID-19 vaccine candidate". Medicago. 16 December 2021. Retrieved 23 December 2021.
  17. ^ "Medicago and GSK announce the approval by Health Canada of COVIFENZ, an Adjuvanted Plant-Based COVID-19 Vaccine". Medicago. 24 February 2022. Retrieved 24 February 2022.

Media files used on this page

Coronavirus. SARS-CoV-2.png
Author/Creator: Alexey Solodovnikov (Idea, Producer, CG, Editor), Valeria Arkhipova (Scientific Сonsultant), Licence: CC BY-SA 4.0
Scientifically accurate atomic model of the external structure of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), a strain (genetic variant) of the coronavirus that caused Coronavirus disease (COVID-19), first identified in Wuhan, China, during December 2019

Each separate locus (amorphous blob) is an atom of:

  cobalt: membrane
  crimson: E protein
  green: M protein
  orange: glucose (glycan)
  turquoise : S (spike) glycoprotein
SARS-CoV-2 (Wikimedia colors).svg
Author/Creator: Geraki, Licence: CC BY-SA 4.0
SARS-CoV-2 logo in Wikimedia colors
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SVG remake of proposal for Scholia logo (File:Scholia logo.png by User:Theklan).
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The rod of Asclepius as depicted in the WHO logo.
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Author/Creator: User:FoeNyx © 2004 (artistic illustration), Licence: CC-BY-SA-3.0
VIH - HIV / SIDA - AIDS viruses.
Nicotiana benthamiana plant.jpg
Nicotiana benthamiana, whole plant
Nicotiana benthamiana leaf.jpg
Author/Creator: unknown, Licence: PD