Pfizer may be the favorite, but Canada has their bets covered

Pfizer and BioNTech surprised the world and gave it hope with the preliminary results of the Phase 3 clinical trial of their coronavirus vaccine.

They announced on November 9 that the first data analysis from the Phase 3 clinical trial, which is still ongoing, showed the vaccine was 90% effective. The unexpectedly high figure has yet to be confirmed in a larger number and over time. The vaccine is simple to manufacture, but its storage is more complex (the vaccine must be stored at very low temperatures). Large-scale production is expected to start shortly.

Laboratories around the world are racing to produce a COVID-19 vaccine. While the milestone is now in sight for Pfizer and BioNTech, the World Health Organization (WHO) lists 202 candidate vaccines, 47 of which are in human trials.

Canada hasn’t put all of its eggs in one basket in its plan to protect Canadians from the novel coronavirus. In addition to Pfizer and BioNTech, it has signed six other contracts: Moderna, Sanofi and GlaxoSmithKline, Johnson & Johnson, Novavax, AstraZeneca and Medicago. Canada recently announced that it had reserved 56 million additional doses of the vaccine from Pfizer and BioNTech, in addition to the 20 million doses it had already purchased, bringing its order to 76 million.

Canada has secured access to a total of 414 million doses of COVID-19 vaccines from multiple sources. More importantly, Canada has ensured that it has diversified the types of vaccines it will have.

Scientists are using several platforms to develop COVID-19 vaccines. Some candidate vaccines in clinical trials exploit mechanisms already used in other vaccines. Others rely on innovative approaches that have never been tested before. Here is an overview of the different types of vaccines.

Inactivated vaccines

Inactivated vaccines have been used since the 1880s. The viruses in these vaccines have been rendered inactive by chemical treatment, such as with candidate SARS-CoV-2 vaccines, or by physical treatment.

With this type of vaccine, the immune system encounters the virus in its entirety. It can mount a defense when it detects the viral spike protein (also called spicule or protein S), envelope and nucleoprotein.

Currently, seven inactivated vaccine candidates are being tested in humans. Of these, three are in Phase 3 clinical trials. Unlike Phase 1 and Phase 2, which are used to evaluate a vaccine’s tolerability, safety, and ability to induce an immune response, a Phase 3 clinical trial allows scientists to test its effectiveness.

Recombinant proteins

Recombinant protein vaccines fall into two categories: subunit vaccines and virus-like particle vaccines.

For subunit protein vaccines, a viral protein is produced in large quantities in a living “factory”, such as a bacterium, plant, mammal or insect cell. When the viral protein is presented to the immune system, it triggers a reaction.

The 13 candidate vaccine subunits currently in clinical trials 1, 2, or 3 are composed of the entire spike protein or a specific portion of the spike protein called the “receptor binding domain”.

Vaccines with virus-like particles are composed of a set of viral proteins that mimic the shape of the virus. This “pseudo-virus” particle is an empty shell, devoid of genetic and non-infectious material, but this does not prevent the immune system from recognizing it.

Vector viral vaccines

This approach is based on the use of a virus that is not pathogenic or of little danger to humans. In the case of the 12 vaccine candidates of this type currently being studied in humans, the viral vectors are mainly adenoviruses. They represent a large group of viruses that can cause colds and conjunctivitis, among other symptoms.

Used as Trojan horses, these viruses are modified to express the SARS-CoV-2 spike protein after vaccination. Vector viral vaccines are a recent strategy but have been used in the development of the Ebola virus vaccine.

RNA and DNA vaccines

Despite the differences in their composition, DNA and mRNA (messenger RNA) both contain genetic information for the production of proteins. While an RNA molecule can directly produce that information, DNA requires an intermediate transcription step.

RNA or DNA vaccine candidates differ from other strategies in two ways. First, it’s a new strategy: There are no DNA or RNA vaccines on the market. Second, they are the only vaccine candidates composed solely of genetic material.

In the case of RNA vaccines, the messenger RNA molecules are wrapped in lipid nanoparticles. Once the vaccine is injected, the RNA serves as a template for the body’s cells to produce a viral protein, the spike protein, to be precise.

DNA vaccines, on the other hand, are made up of a circular DNA (called a plasmid). This DNA will be transcribed into RNA, which will again serve as a template.

Six DNA vaccine candidates are currently being tested in humans, two of which are in Phase 3. The five DNA vaccine candidates are in Phase 1 and 2 clinical trials.

Canada in the vaccine race

Below is an overview of each company that has an agreement with the federal government, the type of vaccine being developed, and the number of reserved doses from Canada.

Pfizer / BioNTech: 76 million reserved doses

BioNTech in Germany and Pfizer in the United States are jointly developing an RNA vaccine. This candidate codes for the production of the spike protein.

The Phase 3 clinical trial is continuing with over 43,000 patients in the United States, Argentina, Brazil, Germany, Turkey and South Africa. The vaccine is said to be over 90% effective and caused no serious side effects.

Despite these encouraging preliminary results, Pfizer and BioNTech have not yet crossed the line. Detailed data have not been published and questions remain, including the age and risk factors of vaccinated individuals and the duration of protection. The clinical trial is ongoing and further data will be analyzed.

Modern: 56 million reserved doses

The candidate vaccine from Moderna, a US-based biotechnology company, is an RNA vaccine. Once injected, it allows for the expression of the spike protein. Currently in Phase 3 clinical trials, the vaccine is being tested on 30,000 individuals in different regions of the United States.

Johnson & Johnson: 38 million reserved doses

Johnson & Johnson’s candidate is a viral vector vaccine composed of a human adenovirus that has been modified to make it unable to multiply, but capable of expressing the SARS-CoV-2 spike protein. The Phase 3 clinical trial, which started in September 2020, is taking place in several countries and will involve 60,000 participants.

AstraZeneca / University of Oxford: 20 million reserved doses

The University of Oxford is collaborating with AstraZeneca on a viral vector vaccine. The vaccine candidate is composed of a modified chimpanzee adenovirus that expresses the spike protein. It is in Phase 3 clinical trials.

Novavax: 76 million reserved doses

The vaccine candidate from Novavax, a US company, is based on the recombinant protein strategy. It is made up of the spike protein and an adjuvant, a booster used in vaccines to boost the immune response. The Phase 3 clinical trial started in September 2020 and involves 10,000 participants in the UK.

Sanofi / GSK: 72 million reserved doses

The candidate of French company Sanofi and British giant GlaxoSmithKline (GSK) is composed of an adjuvant and recombinant version of the spike protein, produced in a living factory (baculovirus). Phase 1 and 2 clinical trials are currently testing its safety, tolerability and ability to induce an immune response.

Medicago: 76 million reserved doses

Developed by the Québec-based Medicago company, this candidate vaccine is composed of virus-like particles. These are produced in bacteria-infected plants that have been genetically engineered to produce different SARS-CoV-2 proteins. These plants thus become production plants.

Researchers can extract the particles from the leaves and purify them. Medicago’s vaccine candidate is currently in clinical trials and the results are also promising.