tetano
Editor, Senior Moderator
Elife
. 2022 Mar 15;11:e75228.
doi: 10.7554/eLife.75228.
Boosting of cross-reactive antibodies to endemic coronaviruses by SARS-CoV-2 infection but not vaccination with stabilized spike
Andrew R Crowley[SUP] #[/SUP][SUP] 1 [/SUP], Harini Natarajan[SUP] #[/SUP][SUP] 1 [/SUP], Andrew P Hederman[SUP] 2 [/SUP], Carly A Bobak[SUP] 3 [/SUP], Joshua A Weiner[SUP] 2 [/SUP], Wendy Wieland-Alter[SUP] 4 [/SUP], Jiwon Lee[SUP] 2 [/SUP], Evan M Bloch[SUP] 5 [/SUP], Aaron A R Tobian[SUP] 5 [/SUP], Andrew D Redd[SUP] 6 7 [/SUP], Joel N Blankson[SUP] 6 [/SUP], Dana Wolf[SUP] 8 [/SUP], Tessa Goetghebuer[SUP] 9 10 [/SUP], Arnaud Marchant[SUP] 9 [/SUP], Ruth I Connor[SUP] 4 [/SUP], Peter F Wright[SUP] 4 [/SUP], Margaret E Ackerman[SUP] 1 2 3 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2; antibodies; conformation; epitope; human; immunology; infectious disease; inflammation; microbiology; neutralization; vaccine.
. 2022 Mar 15;11:e75228.
doi: 10.7554/eLife.75228.
Boosting of cross-reactive antibodies to endemic coronaviruses by SARS-CoV-2 infection but not vaccination with stabilized spike
Andrew R Crowley[SUP] #[/SUP][SUP] 1 [/SUP], Harini Natarajan[SUP] #[/SUP][SUP] 1 [/SUP], Andrew P Hederman[SUP] 2 [/SUP], Carly A Bobak[SUP] 3 [/SUP], Joshua A Weiner[SUP] 2 [/SUP], Wendy Wieland-Alter[SUP] 4 [/SUP], Jiwon Lee[SUP] 2 [/SUP], Evan M Bloch[SUP] 5 [/SUP], Aaron A R Tobian[SUP] 5 [/SUP], Andrew D Redd[SUP] 6 7 [/SUP], Joel N Blankson[SUP] 6 [/SUP], Dana Wolf[SUP] 8 [/SUP], Tessa Goetghebuer[SUP] 9 10 [/SUP], Arnaud Marchant[SUP] 9 [/SUP], Ruth I Connor[SUP] 4 [/SUP], Peter F Wright[SUP] 4 [/SUP], Margaret E Ackerman[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 35289271
- DOI: 10.7554/eLife.75228
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.
Keywords: SARS-CoV-2; antibodies; conformation; epitope; human; immunology; infectious disease; inflammation; microbiology; neutralization; vaccine.