Boosting of cross-reactive antibodies to endemic coronaviruses by SARS-CoV-2 infection but not vaccination with stabilized spike

• DOI: 10.7554/elife.75228
• Publication Date: 2022-03-15T00:01:14Z
• Authors: Andrew R Crowley; Harini Natarajan; Andrew P Hederman; Carly A Bobak; Joshua A Weiner; Wendy Wieland-Alter; Jiwon Lee; Evan M Bloch; Aaron AR Tobian; Andrew D Redd; Joel N Blankson; Dana Wolf; Tessa Goetghebuer; Arnaud Marchant; Ruth I Connor; Peter F Wright; Margaret E Ackerman
• Keywords: conformation; COVID-19 Vaccines; QH301-705.5; infectious disease; Science; Cross Reactions; Antibodies, Viral; Article; immunology; Immunology and Inflammation; Antibody Specificity; Neutralization Tests; vaccine; Immunologie; antibodies; Humans; human; Biology (General); epitope; SARS-CoV-2; microbiology; Q; Vaccination; Neurosciences cognitives; R; COVID-19; Sciences bio-médicales et agricoles; neutralization; Immunoglobulin A; 3. Good health; Immunoglobulin M; inflammation; Immunoglobulin G; Host-Pathogen Interactions; Spike Glycoprotein, Coronavirus; Medicine; Microbiologie et protistologie [bacteriol.virolog.mycolog.]

Preexisting antibodies to endemic coronaviruses (CoV) that cross-react with SARS-CoV-2 have the potential to influence the antibody response to COVID-19 vaccination and infection for better or worse. In this observational study of mucosal and systemic humoral immunity in acutely infected, convalescent, and vaccinated subjects, we tested for cross-reactivity against endemic CoV spike (S) protein at subdomain resolution. Elevated responses, particularly to the β-CoV OC43, were observed in all natural infection cohorts tested and were correlated with the response to SARS-CoV-2. The kinetics of this response and isotypes involved suggest that infection boosts preexisting antibody lineages raised against prior endemic CoV exposure that cross-react. While further research is needed to discern whether this recalled response is desirable or detrimental, the boosted antibodies principally targeted the better-conserved S2 subdomain of the viral spike and were not associated with neutralization activity. In contrast, vaccination with a stabilized spike mRNA vaccine did not robustly boost cross-reactive antibodies, suggesting differing antigenicity and immunogenicity. In sum, this study provides evidence that antibodies targeting endemic CoV are robustly boosted in response to SARS-CoV-2 infection but not to vaccination with stabilized S, and that depending on conformation or other factors, the S2 subdomain of the spike protein triggers a rapidly recalled, IgG-dominated response that lacks neutralization activity.