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Cross-reactive serum and memory B-cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection

Ge Song, Wan-ting He, Sean Callaghan and 18 more

Nature Communications · 2021 · CC BY

doi:10.1101/2020.09.22.308965

Abstract

Pre-existing immunity to seasonal endemic coronaviruses could have profound consequences for antibody responses to SARS-CoV-2, induced from natural infection or vaccination. A first step to establish whether pre-existing responses can impact SARS-CoV-2 infection is to understand the nature and extent of cross-reactivity in humans to coronaviruses. Here we compare serum antibody and memory B cell responses to coronavirus spike proteins from pre-pandemic and SARS-CoV-2 convalescent donors using binding and functional assays. We show weak evidence of pre-existing SARS-CoV-2 cross-reactive serum antibodies in pre-pandemic donors. However, we find evidence of pre-existing cross-reactive memory B cells that are activated during SARS-CoV-2 infection. Monoclonal antibodies show varying degrees of cross-reactivity with betacoronaviruses, including SARS-CoV-1 and endemic coronaviruses. We identify one cross-reactive neutralizing antibody specific to the S2 subunit of the S protein. Our results suggest that pre-existing immunity to endemic coronaviruses should be considered in evaluating antibody responses to SARS-CoV-2.

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Structural biology of SARS-CoV-2: open the door for novel therapies · 2022
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Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection · 2022
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Longitudinal analysis of humoral immunity against SARS-CoV-2 Spike in convalescent individuals up to 8 months post-symptom onset · 2021
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SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern · 2021
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mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection · 2021
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A conserved immunogenic and vulnerable site on the coronavirus spike protein delineated by cross-reactive monoclonal antibodies · 2021
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Immunity to SARS‐CoV‐2 induced by infection or vaccination · 2021
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Broad betacoronavirus neutralization by a stem helix–specific human antibody · 2021
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Humoral Responses and Serological Assays in SARS-CoV-2 Infections · 2020
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Preexisting and de novo humoral immunity to SARS-CoV-2 in humans · 2020
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