Differential immune imprinting effects of seasonal common cold coronaviruses on breadth of responses to SARS-CoV-2 4766

Abstract Description As novel SARS-CoV-2 variants continue to emerge, it is essential to gain further insight into the impact of imprinting on protective antibody responses. Utilizing a longitudinal healthcare worker cohort with samples collected before and after infection or vaccination, we aimed to determine whether preexisting humoral immunity to seasonal common cold human coronaviruses (hCoVs)—OC43, HKU1, 229E, and NL63—negatively affect the subsequent IgG, IgM, and IgA responses to the Receptor Binding Domain (RBD) of different variants (Wuhan, Alpha, Beta, Gamma, Kappa, Delta, Delta+, Lambda, and Omicron) of SARS-CoV-2 during the initial COVID-19 wave in the US. We developed a novel method of quantifying the breadth of the overall anti-RBD responses for each isotype utilizing the Grantham’s distances between the variant RBD amino acid sequences. The resulting “Breadth Scores”, but not anti-RBD measurements alone, were post-vaccination correlates of protection against breakthrough infections and were independent of age. We found that anti-hCoV Spike levels before COVID-19 had both significant positive and negative effects on Breadth Scores during COVID-19 regardless of demographic factors. Most notably, participants who had higher baseline anti-OC43 Spike IgM levels exhibited significantly lower Breadth Scores during COVID-19 due only to non-Wuhan variant RBD binding. Overall, these data suggest preexisting immunity to hCoVs can affect future responses to ever-evolving SARS-CoV-2 variants. Funding Sources David C. Brice was supported through the American Association of Immunologists Intersect Program for Computational Scientists and Immunologists. Maureen A. McGargill was supported through NIH/NIAID R01AI114728 and CEIRS HHSN272201400006C, ALSAC, and HRTS 3U01AI144616-02S1. Topic Categories Viral Immunology (VIR)