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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere75228
JournaleLife
Volume11
DOIs
StatePublished - Mar 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
‍© Crowley et al.

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