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Pfizer-BioNTech vaccine testing on animals

Several effective and safe vaccines against SARS-CoV-2 are now on the market. They were developed in record time, and are based specifically on inhibiting the virus’ spike (S) surface protein. The S protein, and more particularly the RBD region, binds to the ACE2 region to enable entry of the viral particle into the cell. This trimeric protein (an assembly of 3 S proteins) is the principal target of neutralizing antibodies.

The Pfizer-BioNTech vaccine is one of these current vaccines and is based on mRNA technology (See letter November 23-29 2020). The mRNA, coated in lipid fat, provides instructions to the body to manufacture the entirety or a part of the virus’ S protein. This S protein will then trigger an immune response against the viral protein.

How was the effectiveness of these 2 vaccines determined? Pfizer and BioNTech, in collaboration with institutional laboratories, have just published the first results obtained during their vaccine development but before the onset of clinical trials. Two versions of the vaccine were compared: the BNT162b1, which encodes a trimerized RBD domain, and the BNT162b2, which encodes the full-length S protein, locked in its pre-fusion conformation (See letter January 18-24 2021). These 2 versions were tested firstly on mice, which were immunized with one or the other of the vaccines. An IgG antibody response was detected, as well as a strong response mediated by CD4 T  lymphocytes (T cell helpers that activate other immune cells) and T CD8s (cytotoxics that destroy infected cells). This response was slightly more pronounced with the BNT162b2 version of the vaccine.

This can be represented schematically as follows:

The 2 vaccines were then tested on macaques, with 2 injections at 3 week intervals. Results were similar to those observed in mice with respect to IgG and T cell responses. 41 to 55 days after the second injection, the macaques were infected with SARS-CoV-2. The 2 vaccines gave protection to the animals: a reduction in the viral charge was observed in vaccinated animals, in particular those immunized with the BNT162b2 version.

These initial results were encouraging and led to further clinical testing with the BNT162b2 version of the vaccine and, several months later, the Pfizer-BioNTech mRNA vaccine appeared on the market.

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