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

Ge Song,Jonathan L Torres,James E Voss,Wanting He ,Caroline Ignacio,Fabio Anzanello,Mara Parren,Linlin Yang,Thomas F Rogers ,Nathan Beutler,Sean Callaghan,Deli Huang,Linghang Peng,Davey M Smith ,Sirena Vargas,Andrew B Ward,David Nemazee,Jon Cassell,Dennis R Burton,James Ricketts,Raiees Andrabi

doi:10.1038/s41467-021-23074-3

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.

Highlights

Pre-existing immunity to seasonal endemic coronaviruses could have profound consequences for antibody responses to SARS-CoV-2, induced from natural infection or vaccination
Since individuals who have been infected with SARS-CoV-2 will generally have been infected with endemic HCoVs, we chose to compare COVID-19 and pre-pandemic donors in terms of serum Abs and B-cell receptors (BCRs) with specificity for the spike (S) protein (Supplementary Table 1 summarizes the demographic details of the human cohorts)
The COVID-19 cohort could reveal the effects of SARS-CoV-2 infection on cross-reactive responses

Summary

Introduction

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. We show weak evidence of pre-existing SARS-CoV-2 cross-reactive serum antibodies in prepandemic donors. We find evidence of pre-existing cross-reactive memory B cells that are activated during SARS-CoV-2 infection. Our results suggest that pre-existing immunity to endemic coronaviruses should be considered in evaluating antibody responses to SARS-CoV-2. There is considerable interest in establishing whether Ab or T-cell responses to SARS-CoV-2, through infection or vaccination, might be impacted by pre-existing immunity to other coronaviruses, the endemic coronaviruses (endemic HCoVs), namely the betacoronaviruses (βHCoV), HCoV-HKU1 and HCoV-OC43, and the alphacoronaviruses (α-HCoV), HCoV-NL63 and HCoV-229E, which are responsible for non-severe infections such as common colds[4,5,6,7,8]. A number of studies have reported on cross-reactive T cells and serum Abs[5,7,9,10,11,12], we investigate here both Ab and BCR cross-reactivities

Methods

Results

Conclusion