Cross-reactive Antibody Responses to Coronaviruses Elicited by SARS-CoV-2 Infection or Vaccination

ABSTRACTBackgroundThe newly emerged SARS‐CoV‐2 possesses shared antigenic epitopes with other human coronaviruses. We investigated if COVID‐19 vaccination or SARS‐CoV‐2 infection may boost cross‐reactive antibodies to other human coronaviruses.MethodsPrevaccination and postvaccination sera from SARS‐CoV‐2 naïve healthy subjects who received three doses of the mRNA vaccine (BioNTech, BNT) or the inactivated vaccine (CoronaVac, CV) were used to monitor the level of cross‐reactive antibodies raised against other human coronaviruses by enzyme‐linked immunosorbent assay. In comparison, convalescent sera from COVID‐19 patients with or without prior vaccination history were also tested. Pseudoparticle neutralization assay was performed to detect neutralization antibody against MERS‐CoV.ResultsAmong SARS‐CoV‐2 infection−naïve subjects, BNT or CV significantly increased the anti‐S2 antibodies against Betacoronaviruses (OC43 and MERS‐CoV) but not Alphacoronaviruses (229E). The prevaccination antibody response to the common cold human coronaviruses did not negatively impact the postvaccination antibody response to SARS‐CoV‐2. Cross‐reactive antibodies that binds to the S2 protein of MERS‐CoV were similarly detected from the convalescent sera of COVID‐19 patients with or without vaccination history. However, these anti‐S2 antibodies do not possess neutralizing activity in MERS‐CoV pseudoparticle neutralization tests.ConclusionsOur results suggest that SARS‐CoV‐2 infection or vaccination may potentially modulate population immune landscape against previously exposed or novel human coronaviruses. The findings have implications for future sero‐epidemiological studies on MERS‐CoV.