Journal Article

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

Weiner, Joshua A, Redd, Andrew D, Crowley, Andrew R, Wieland-Alter, Wendy, Lee, Jiwon, Wolf, Dana, Tobian, Aaron AR, Blankson, Joel N, Hederman, Andrew P, Bobak, Carly A, Goetghebuer, Tessa, Natarajan, Harini, Bloch, Evan M, Connor, Ruth I, Wright, Peter F, Marchant, Arnaud, Ackerman, Margaret E

2022

Overview

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.

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Antibodies / Antibodies, Viral - immunology / Antibody response / Antibody Specificity - immunology / Antigenicity / Antigens / conformation / Coronaviridae / Coronaviruses / COVID-19 / COVID-19 - prevention & control / COVID-19 vaccines / COVID-19 Vaccines - immunology / Cross Reactions - immunology / Cross-reactivity / Dengue fever / epitope / Host-Pathogen Interactions - immunology / Humans / Humoral immunity / Hypotheses / Immunogenicity / Immunoglobulin A - immunology / Immunoglobulin G / Immunoglobulin G - immunology / Immunoglobulin M - immunology / Immunology and Inflammation / Infections / Isotypes / Microbiology and Infectious Disease / mRNA / Mucosa / Mucosal immunity / neutralization / Neutralization Tests / Pandemics / Peptides / Proteins / SARS-CoV-2 / SARS-CoV-2 - immunology / Severe acute respiratory syndrome coronavirus 2 / Spike Glycoprotein, Coronavirus - immunology / Spike protein / Vaccination / vaccine