Cross-reactive antibodies elicited to conserved epitopes on SARS-CoV-2 spike protein after infection and vaccination

Sci Rep. 2022 Apr 20;12(1):6496. doi: 10.1038/s41598-022-10230-y.


SARS-CoV-2 is a novel betacoronavirus that caused coronavirus disease 2019 and has resulted in millions of deaths worldwide. Novel coronavirus infections in humans have steadily become more common. Understanding antibody responses to SARS-CoV-2, and identifying conserved, cross-reactive epitopes among coronavirus strains could inform the design of vaccines and therapeutics with broad application. Here, we determined that individuals with previous SARS-CoV-2 infection or vaccinated with the Pfizer-BioNTech BNT162b2 vaccine produced antibody responses that cross-reacted with related betacoronaviruses. Moreover, we designed a peptide-conjugate vaccine with a conserved SARS-CoV-2 S2 spike epitope, immunized mice and determined cross-reactive antibody binding to SARS-CoV-2 and other related coronaviruses. This conserved spike epitope also shared sequence homology to proteins in commensal gut microbiota and could prime immune responses in humans. Thus, SARS-CoV-2 conserved epitopes elicit cross-reactive immune responses to both related coronaviruses and host bacteria that could serve as future targets for broad coronavirus therapeutics and vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral
  • BNT162 Vaccine
  • COVID-19* / prevention & control
  • Epitopes
  • Humans
  • Mice
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus*
  • Vaccination


  • Antibodies, Viral
  • Epitopes
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • BNT162 Vaccine