INTRODUCTION
SARS-CoV-2 is a newly emerged human coronavirus (HCoV) that has rapidly swept through the globe and resulted in significant public health and socioeconomic loss. As a member of the genus Betacoronavirus, SARS-CoV-2 possesses shared epitopes with other HCoVs including the common cold Alphacoronaviruses (229E, NL63) and Betacoronaviruses (OC43, HKU1), as well as two newly emerged Betacoronaviruses, SARS-CoV-1 in 2002 and MERS-CoV in 2012 (1, 2). Prior exposures to common cold HCoVs may provide cross-protective humoral or cell-mediated immunity. However, previous studies showed conflicting results on whether pre-existing antibodies towards common cold HCoVs provide cross-protection against SARS-CoV-2 infection or severe disease outcomes (3, 4, 5, 6). On the other hand, pre-existing memory T cells that are likely elicited in response to common cold CoVs have been consistently associated with cross-protection among SARS-CoV-2-exposed healthcare workers or household contacts (7, 8).
Since 2020, 7.7 billion SARS-CoV-2 infected and re-infected cases have been reported to WHO and 13.5 billion doses of COVID-19 vaccines have been administered globally. The extensive exposure to SARS-CoV-2 through infection and immunization may substantially affect the population immune landscape and susceptibility to other HCoVs. The pre-existing immunity to common cold HCoVs may potentially result in back-boosting of antibodies against the conserved S2 epitopes upon SARS-CoV-2 infection or vaccination as reported previously (9, 10, 11, 12, 13). In addition, de novo antibody response against SARS-CoV-2 may also cross-react with other HCoVs (10, 14). A better understanding on the cross-reactive antibody responses may provide guidance on the development of pan-coronavirus vaccines.
While the spike-encoding mRNA and the whole-virion inactivated vaccines have been the main COVID-19 vaccines administered globally to date, most studies so far have focused on the effect of mRNA vaccines. The mRNA vaccines adopted the pre-fusion conformation of the spike protein while the pre-fusion and post-fusion conformations have been reported for the inactivated vaccines (15). Inactivated vaccines also contain additional SARS-CoV-2 structural proteins that may stimulate humoral or cell-mediated immunity. Using pre- and post- vaccination sera, we firstly compared the cross-reactive antibody responses against different HCoVs elicited by mRNA and inactivated COVID-19 vaccines in individuals previously infection-naïve for SARS-CoV-2. We also separately investigated cross-reactive antibody response in convalescent sera of SARS-CoV-2 patients with or without prior vaccination history.