The Government of Canada has now made six deals to acquire COVID-19 vaccines currently in development. The deals secure about 280 million doses (most vaccines will require 2 injections) at an estimated cost of $1 billion (Harris K. CBC, 25 September 2020). Monies paid are to ensure a supply of vaccine and will not be fully refunded if the vaccines are ineffective or fail to receive Health Canada approval (Canadian Press, 22 September 2020). All of the vaccines are in late-stage development but none has yet demonstrated efficacy.
The following summarizes the vaccines for which the Canadian government has made deals.
Novovax (NVX-CoV2373): A protein subunit vaccine that uses recombinant SARS-CoV-2 Spike protein nanoparticles as the antigen. Administered with an adjuvant to boost the immune response. A phase III trial was announced on September 24. Planned enrollment is 10,000 subjects in the U.K. Subjects will receive placebo or two intramuscular injections on days 0 and 21. The study’s two primary endpoints are PCR-confirmed COVID-19 and first occurrence of moderate or severe COVID-19. Health Canada has reserved 76 million doses.
Moderna (mRNA-1273): mRNA coding for viral genes is used to induce host cells to produce viral antigen (full-length Spike protein); mRNA is delivered in liposomes. A phase III trial began in July in collaboration with the U.S. National Institute of Allergy and Infectious Diseases and the Biomedical Advanced Research and Development Authority (BARDA). The event-driven trial plans to enroll 30,000 subjects in the U.S. Subjects will receive placebo or two vaccine injections on days 0 and 21. The primary endpoint is prevention of symptomatic COVID-19. In October, the vaccine was put into rolling submission with Health Canada so that regulators can evaluate ongoing data as they become available. To date, no RNA vaccine has ever received approval for human use. Health Canada has reserved 20 million doses with an option to purchase an additional 36 million doses.
Pfizer/BioNTech (BNT162b2): Similar to the Moderna vaccine. Uses modified mRNA encoding for full-length Spike protein encased in a lipid nanoparticle. Requires two doses. Phase I data have been prepublished (Walsh et al. www.medrxiv.org/content/10.1101/2020.08.17.20176651v2.full.pdf). A phase II/III study began in July and expects to enroll 30,000 subjects. Put into rolling submission with Health Canada in October. As noted previously, no RNA vaccine has been shown to be effective in humans. Health Canada has reserved up to 20 million doses.
Janssen (Ad26.COV2-S; JNJ-78436735): A viral vector vaccine that uses non-replicating human adenovirus to deliver Spike protein for expression by host cells. May require only one inoculation. A phase III trial began in the U.S. in September but was paused in October following the report of “unexplained illness” in one study subject. No further details were provided. A concern with using a live vector is that it may induce an immune response to the vector and reduce the effectiveness of the vaccine. It should be noted that only one viral vector vaccine (a Janssen Ebola vaccine) has ever been approved for human use. Health Canada has reserved up to 38 million doses.
University of Oxford/Astra Zeneca (ChAdOx1; AZD1222): Similar to the Janssen vaccine but uses a non-replicating chimpanzee adenovirus as the vector; this may lower the risk of an immune reaction to the vector. The virus encodes the Spike protein. The phase III trial was paused briefly following the report of a case of transverse myelitis; the trial has since resumed. Health Canada has reserved 20 million doses.
Sanofi/GlaxoSmithKline: Uses Sanofi’s recombinant technology (used for its influenza vaccine) to produce a Spike protein subunit vaccine; GSK is providing the adjuvant. Similar to the Novovax vaccine. Began phase I/II testing in September. Phase III testing is expected to begin in December. Health Canada has reserved up to 72 million doses. Sanofi also has an mRNA COVID vaccine in earlier-stage development.
The Canadian government strategy is to obtain a range of vaccines in the hope that at least one will be effective, although the six candidates only employ three different technologies (protein subunit, RNA, viral vector) and one antigen (Spike protein). The government also signed an Interim Order in September that allows for the importation and stockpiling of vaccines that have not yet been approved by Health Canada (called prepositioning). The government is required to enter into a contract to procure a product before it can be prepositioned.
Source: Vaccine quantities from Chung E. CBC, 2 September 2020.