Host predictors of broadly cross-reactive antibodies against SARS-CoV-2 variants of concern differ between infection and vaccination.

ABSTRACT

BACKGROUND: Following SARS-CoV-2 infection or vaccination there is significant variability between individuals in protective antibody levels against SARS-CoV-2, and within individuals against different virus variants. However, host demographic or clinical characteristics that predict variability in cross-reactive antibody levels are not well-described. These data could inform clinicians, researchers, and policy makers on the populations most likely to require vaccine booster shots. METHODS: In an institutional review board-approved prospective observational cohort study of staff at St. Jude Children's Research Hospital, we identified participants with plasma samples collected after SARS-CoV-2 infection, after mRNA vaccination, and after vaccination following infection, and quantitated IgG levels by ELISA to the spike receptor binding domain (RBD) from five important SARS-CoV-2 variants (Wuhan Hu-1, B.1.1.7, B.1.351, P.1 and B.1.617.2). We used regression models to identify factors that contributed to cross-reactive IgG against one or multiple viral variants. RESULTS: Following infection, a minority of the cohort generated cross-reactive antibodies, IgG antibodies that bound all tested variants. Those that did had increased disease severity, poor metabolic health, and were of a particular ancestry. Vaccination increased the levels of cross-reactive IgG levels in all populations including immunocompromised, elderly and persons with poor metabolic health. Younger people with a healthy weight mounted the highest responses. CONCLUSIONS: Our findings provide important new information on individual antibody responses to infection/vaccination that could inform clinicians on the populations that may require follow-on immunization.