CoVLP

Last updated

CoVLP
Vaccine description
Target SARS-CoV-2
Vaccine type Virus-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]

Contents

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 January 2021, the Medicago CoVLP vaccine candidate was in a Phase II-III clinical trial in Canada and the United States, involving 30,918 participants. [7]

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. [8] [9]

Manufacturing

N. benthamiana plant used by Medicago as a "minifactory" for rapid production of coVLP Nicoatiana benthamiana plant.jpg
N. benthamiana plant used by Medicago as a "minifactory" for rapid production of coVLP
Nicotiana benthamiana, leaf Nicotiana benthamiana leaf.jpg
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] [10]

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). [8] 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. [11] [12]

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. [13] Adults (18–55 years, n = 180) 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. [14]

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] [15] [9] The Phase 3 portion is an event-driven, randomized, observer-blinded, crossover placebo-controlled design that will evaluate the efficacy and safety of the CoVLP formulation, compared to placebo.

Related Research Articles

<i>Nicotiana benthamiana</i> Species of flowering plant

Nicotiana benthamiana is a close relative of tobacco and species of Nicotiana indigenous to Australia.

H5N1 clinical trials

H5N1 clinical trials are clinical trials concerning H5N1 vaccines, which are intended to provide immunization to influenza A virus subtype H5N1. They are intended to discover pharmacological effects and identify any adverse reactions the vaccines may achieve in humans.

Cervarix is a vaccine against certain types of cancer-causing human papillomavirus (HPV).

Valneva SE is a French biotech company headquartered in Saint-Herblain, France, developing and commercializing vaccines for infectious diseases. It has manufacturing sites in Livingston, Scotland; Solna, Sweden and Vienna, Austria, with other offices in France, Canada and the United States.

COVID-19 vaccine Designed to provide acquired immunity against SARS-CoV-2

A COVID‑19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 (COVID‑19). Prior to the COVID‑19 pandemic, an established body of knowledge existed about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). This knowledge accelerated the development of various vaccine platforms during early 2020. The initial focus of SARS-CoV-2 vaccines was on preventing symptomatic, often severe illness. On 10 January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID, and by 19 March, the global pharmaceutical industry announced a major commitment to address COVID-19. The COVID‑19 vaccines are widely credited for their role in reducing the spread, severity, and death caused by COVID-19.

Medicago Inc. Canadian biotechnology company

Medicago Inc. is a privately-owned Canadian biotechnology company focused on the discovery, development, and commercialization of virus-like particles using plants as "bioreactors" to produce proteins as candidate vaccines and medications. By using live plant leaves as hosts in the discovery and manufacturing process, the Medicago "Proficia" technology has the goal to create a rapid, high-yield system for its product candidates.

CoronaVac Vaccine against COVID-19

CoronaVac, also known as the Sinovac COVID-19 vaccine, is an inactivated virus COVID-19 vaccine developed by the Chinese company Sinovac Biotech. It was Phase III clinical trialled in Brazil, Chile, Indonesia, the Philippines, and Turkey and relies on traditional technology similar to BBIBP-CorV and Covaxin, other inactivated-virus COVID-19 vaccines. CoronaVac does not need to be frozen and both the final product and the raw material for formulating CoronaVac can be transported refrigerated at 2–8 °C (36–46 °F), temperatures at which flu vaccines are kept.

Covaxin Vaccine against COVID-19

Covaxin is an inactivated virus-based COVID-19 vaccine developed by Bharat Biotech in collaboration with the Indian Council of Medical Research.

Valneva COVID-19 vaccine Vaccine candidate against COVID-19

Valneva COVID-19 vaccine, also known as the VLA2001 and VLA2101, is a COVID-19 vaccine candidate developed by French biotechnology company Valneva SE in collaboration with American company Dynavax Technologies.

ZF2001 Vaccine against COVID-19

ZF2001, trade-named ZIFIVAXor "ZF-UZ-VAC-2001, 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.

CureVac COVID-19 vaccine Vaccine candidate against COVID-19

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.

SCB-2019 Vaccine candidate against COVID-19

SCB-2019 is a protein subunit COVID-19 vaccine candidate developed by Clover Biopharmaceuticals using an adjuvant from Dynavax. Positive results of Phase I trials for the vaccine were published in The Lancet and the vaccine completed enrollment in its Phase II/III trials in July 2021, with efficacy results expected to be announced by Q3 2021. SCB-2019 is being funded by CEPI as part of COVAX and has received advanced purchase orders from GAVI for 400 million doses.

Sanofi–GSK COVID-19 vaccine Vaccine candidate against COVID-19

The Sanofi–GSK COVID-19 vaccine code-named VAT00002 and VAT00008 is a COVID-19 vaccine candidate developed by Sanofi Pasteur and GSK.

Nanocovax Vaccine candidate against COVID-19

Nanocovax is a Vietnamese COVID-19 vaccine candidate developed by Nanogen Pharmaceutical Biotechnology JSC. It is a subunit vaccine.

MVC COVID-19 vaccine Vaccine against COVID-19

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 in Taiwan, American company Dynavax Technologies and National Institute of Health.

Walvax COVID-19 vaccine Vaccine candidate against COVID-19

ARCoV, also known as the Walvax COVID-19 vaccine, is an mRNA COVID-19 vaccine candidate developed by Walvax Biotechnology, Suzhou Abogen Biosciences, and the PLA Academy of Military Science. It is in Phase III trials in Mexico.

Corbevax Vaccine candidate against COVID-19 and infertility

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 American company Dynavax Technologies (DVAX). It is a protein subunit vaccine.

Razi Cov Pars Vaccine candidate against COVID-19

Razi Cov Pars is a COVID-19 vaccine candidate developed by Razi Vaccine and Serum Research Institute.

COVAX-19 Vaccine candidate against COVID-19

COVAX-19 is a recombinant protein-based COVID-19 vaccine candidate developed by South Australian based biotech company, Vaxine. It is under clinical trial in Iran in collaboration with CinnaGen.

GBP510 Vaccine candidate against COVID-19

GBP510 is a COVID-19 vaccine candidate developed by SK Bioscience and GSK.

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.
  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. 1 2 "GSK partners with Medicago to develop plant-based Covid-19 vaccine". Pharmaceutical Technology. 8 July 2020. Retrieved 3 August 2020.
  9. 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.
  10. "VLP technologies and production platform". Medicago. Retrieved 30 January 2021.
  11. 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.
  12. Lucy Parsons (8 July 2020). "GSK signs deal with Medicago for COVID-19 vaccine". PMLive. Retrieved 30 January 2021.
  13. 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
  14. 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.
  15. "Medicago and GSK start Phase 3 trial of adjuvanted COVID-19 vaccine candidate". GlaxoSmithKline. 16 March 2021. Retrieved 13 April 2021.