SARS-CoV-2 virus infection in vaccinated vulnerable populations and the potential for variant emergence

Vulnerable populations including immunosuppressed individuals and those of older ages typically have less effective vaccine responses. Additionally, reports have surfaced that SARS-CoV-2 infection in particular vulnerable populations leads to viral variant emergence. Our research project will investigate the effectiveness of vaccination or previous infection in older frail individuals as well as HIV+ people to prevent infection with the SARS-CoV-2 variants of concern (VOC). As we are investigating the ability of antibodies elicited after vaccination to neutralize SARS-CoV-2 viruses, we will also determine the molecular signature of viruses that have the ability to escape antibody neutralization. We hypothesize that vaccinated vulnerable populations will be less protected from the variants which will enable a selection pressure capable of driving virus evolution and new variants. For our study we have established cohorts of infected and vaccinated vulnerable populations (older frail individuals and those HIV+) from Halifax, Nova Scotia; Sardinia, Italy; and Kigali, Rwanda. Plasma collected from these cohorts will be tested in virus neutralization assays and virus escape assays to identify protection as well as escape viruses. Viral variant signatures will be analyzed by next generation sequencing methods and our bioinformatic pipeline to identify regions of change on the virus that might affect antibody binding. To validate our work, we will perform challenge studies in vaccinated aged hamsters. Two important outcomes will result from this study: 1.Potential effectiveness of COVID-19 vaccines to protect against VOCs in vulnerable groups. 2.The signature of potential future VOCs. The VOC signature can be used to screen for potential VOCs in the community and inform vaccine reformulation.