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SARS-CoV-2 is a novel beta coronavirus that emerged in 2019 and is responsible for the on-going pandemic (COVID-19). The humoral immune response consists of antibodies of multiple isotypes that can block viral progression. We wanted to characterize antibody response to a vaccine (Pfizer, BNT162b2) in a group of Children’s Mercy employees. We compared responses of people with previous SARS-CoV-2 infection (COVID+) to those with no known previous infection (COVID-). We measured antibody isotypes IgG, IgM and IgA to SARS-CoV-2 spike protein subunit 1 (S1), spike protein subunit 2 (S2), receptor binding domain (RBD), and nucleocapsid (NP) at baseline (week 0), after the first dose (week 3) and after the second dose (week 7). At baseline, the COVID+ group had levels of IgG to S1, S2, RBD, NP that were significantly higher than the COVID- group. After the first dose, the COVID+ group continued to show significantly higher IgG levels to S1, S2, RBD, NP. The COVID- group had variable IgG levels, suggesting that protection after the first vaccine is not guaranteed. Due to the extremely high levels of IgG in COVID+ group after the first dose, these individuals may only require one vaccination. At the final time point, COVID- had similar IgG levels to S1, S2, and RBD as the COVID+ group; indicating that protection from the second vaccination was complete. Neutralizing antibody levels were also determined throughout the course of immunization. The COVID+ group had significantly higher neutralizing antibodies compared to the COVID- group at baseline and after the first dose. After the second dose, nearly all participants had high (<85%) neutralizing antibodies present. Finally, using the spike protein we identified regions of high IgG reactivity that may be excellent targets for future vaccine design.

Antibodies can target conserved sites on the virus and cross-react with multiple related coronaviruses. Children are often more recently infected with seasonal coronaviruses than adults and are more resistant to severe COVID-19 disease. It was previously reported that children have high levels of cross-reactive antibodies to SARS-CoV-2 despite never having infection. We wanted to confirm if children have higher levels of cross-reactive antibodies than adults, and further characterize these responses. We measured antibody isotypes in children never exposed to SARS-CoV-2 (cohort from 2017/2016). We found that a portion of children had pre-existing cross-reactive antibodies, and that these antibodies were also present in some adults with no prior history of SARS-CoV-2 infection.

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Characterizing Differential Antibody Responses To Covid-19 Vaccine And Pre-Existing Immunity To Covid-19