Pillar 4
Functional Genomics & Structure-Function of VOCs

Neutralizing antibodies are produced as an immune response to vaccination or infection.  The term “neutralizing” refers to the ability of some antibodies to block a pathogen from infecting or entering host cells.  This neutralizing activity depends on the ability of these antibodies to recognize proteins that belong to the pathogen.  Immunization with vaccines encoding the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is designed to instruct our immune systems to produce antibodies that recognize SARS-CoV-2 spike and block infection.  However, SARS-CoV-2 variants of concern (VOC) had emerged with mutations that reduced the ability of antibodies to recognize and neutralize SARS-CoV-2 spike and prevent infection.

The first vaccine dose was administered in Canada on Dec 14, 2021, and still by late March 2021, very few Canadians had received a second dose of vaccine.  At that time, it was estimated that up to two-thirds of COVID-19 cases in the Canadian province of Ontario were due to the variants Alpha, Beta and Gamma whereas in Sept 2021 nearly all infections in Ontario were due to the Delta variant.  This study was conducted to understand the levels of neutralizing antibodies and the breadth of antibody protection against wild-type SARS-CoV-2 and VOCs in Canadian blood donors during the first 3 months of 2021.  From 4,500 samples collected between January and March 2021, a subset of 320 samples was divided into groups based on known vaccination status and presumed infection.  Samples were randomly selected for testing from these sub-groups.  We conducted neutralization assays using viral-like particles (VLPs) to measure the neutralizing capacity of antibodies against wild-type as well as VOCs, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2).  The Delta variant was included in this analysis because it emerged as a prevalent variant during the study, and its inclusion enabled the research team to compare how vaccines and infections that were acquired during the January to March 2021 period were able to produce a neutralizing capacity against an emergent Delta variant.

Elevated levels of neutralizing capacity in vaccinated blood donors were detected; however, neutralization capacities against SARS-CoV-2 VOCs were reduced compared to that of the wild-type strain.  In the vaccinated and/or infected groups, neutralization of Beta was detectable, albeit showed the least neutralization capacity when compared to wild-type strain.  These same donor groups also showed detectable, though reduced, neutralization capacity against Alpha, Gamma, and Delta VOCs compared to wild-type strain.  However, in the unvaccinated and uninfected group, we did not detect neutralizing capacity against wild-type or VOCs.  This study is important because it indicates that vaccination (and prior infection) is associated with a broad neutralizing antibody capacity of donor plasma against SARS-CoV-2 wild-type strain and Alpha, Beta, Gamma, and Delta VOCs.

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SARS-CoV-2 virus-like particle neutralizing capacity in blood donors depends on serological profile and donor-declared SARS-CoV-2 vaccination history. Steven J. Drews, Queenie Hu, Reuben Samson, Kento T. Abe, Bhavista Rathod, Karen Colwill, Anne-Claude Gingras, Qi-Long Yi, Sheila F. O’Brien. Microbiology Spectrum. 2022.02.23.02262-21; https://journals.asm.org/doi/10.1128/spectrum.02262-21