INVESTIGATING ANTIBODY AVIDITY IN SARS-COV-2 NAÏVE AND CONVALESCENT VACCINEES

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2022

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Over the past two years, SARS-CoV-2 has had a devastating impact across the world. Despite the historic success of the multiple SARS-CoV-2 vaccines, additional research is needed to further understand the underlying mechanisms of protection. While many studies focus primarily on neutralizing antibody titers, another aspect of humoral immunity that is often overlooked is antibody avidity. Avidity, the total binding strength of all interactions between an antibody and antigen, is important to consider in the context of vaccination because it provides an important measure of antibody maturation and development. To date, there is no “gold standard” approach to measure antibody avidity. Solid-state immunoassays such as ELISAs are commonly modified with a chaotropic agent capable of disrupting antigen-antibody interactions. This overall focus of this study is to measure and compare antibody avidity in SARS-CoV-2 naïve and convalescent vaccinees. To do so we optimized an ammonium thiocyanate-modified multiplex immunoassay that can be used to measure SARS-CoV-2 antibody avidity. We found that standardizing antibody concentrations is an important step when measuring antibody avidity. This helps to prevent oversaturation of the assay and ensures that avidity can be measured and compared between sera with different antibody populations. Additionally, we used this assay to measure longitudinal sera collected from SARS-CoV-2 naïve and convalescent vaccinees to investigate the relationship between natural infection and vaccination. Sera were collected prior to vaccination, >14 days post-dose 1, and >14 days post-dose 2 and individuals were grouped based on whether they had SARS-CoV-2 infection prior to vaccination. Additionally, in both the naïve and convalescent groups, antibody avidity increased following each vaccine dose. A single antigen exposure in the convalescent group (natural infection), generated higher antibody avidity than a single vaccine dose in the naïve group. Avidity was also higher following two antigen exposures in the convalescent group (natural infection + a single vaccine dose) compared to two vaccine doses in the naïve group. Our assay demonstrates differences in the antibody response following natural infection and vaccination which opens the door for further investigation into these differences.

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Biology, Virology, Immunology, Avidity, COVID-19, SARS-CoV-2, Vaccines

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73 pages

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