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.