Variants of concern: escape from infection- and vaccination-induced immunity in older adults

Gingras, Anne-Claude | $496,159

Ontario Sinai Health System 2021 CIHR Operating Grant

One year after the beginning of the COVID‑19 pandemic, much has been learned on the biology of the virus that causes it, SARS-CoV-2. We know that it can enter human cells through the binding of the virus spike protein to a protein at the surface of human cells called ACE2. In response to viral infection, the body tries to defend itself by producing antibodies, including a class of antibodies that attach to the virus spike protein and prevent it from binding to the ACE2 protein on human cells (we call these “neutralizing antibodies”). The vaccines approved in Canada work by mimicking the viral spike protein, inducing the production of neutralizing antibodies. While the vaccines have been extremely successful to drive immunity to the originally circulating strain, RNA viruses like SARS-CoV-2 make mistakes when they replicate their genetic material; these mistakes are called “mutations”. Often, the mutations do not change the virus properties, or negatively affect the virus, but sometimes, the mutations offer the virus some selective advantages. Some of the mutations have caused spike to bind more tightly to ACE2 – this is the case of the B.1.1.17 strain first identified in the UK, while some of the mutations make the virus less efficiently “neutralized” by antibodies. These viruses that have mutations that potentially render them more dangerous are called “Variants of Concern”, or VOCs, and we expect that new such variants will continue to emerge. Here, we want to study to what extent the different variants that are circulating in Canada are efficiently “neutralized” by the immune system of older adults, because this population is likely to build lower levels of antibodies following vaccination and is more susceptible to severe disease.

With funding from the Government of Canada

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