AUTHOR=Hu Caiqin , Wang Zheng , Ren Li , Hao Yanling , Zhu Meiling , Jiang He , Wang Shuo , Li Dan , Shao Yiming TITLE=Pre-existing anti-HCoV-OC43 immunity influences the durability and cross-reactivity of humoral response to SARS-CoV-2 vaccination JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 12 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.978440 DOI=10.3389/fcimb.2022.978440 ISSN=2235-2988 ABSTRACT=Purpose In order to properly understand whether prior seasonal human coronavirus (HCoVs) immunity could impacts potential cross-reactivity of humoral responses induced by SARS-CoV-2 vaccine, thereby devising universal coronavirus vaccines for the future outbreaks. Methods we performed the ELISA (enzyme-linked immunosorbent assay) to quantify the immunoglobulin G (IgG) antibody levels to spike (S) protein and S1 subunit of HCoVs (HCoV-OC43, HCoV-HKU1, HCoV-NL63 and HCoV-229E), and ELISA (anti-RBD and anti-nucleoprotein(N)), chemiluminescence immunoassay assays (anti-RBD), pseudovirus neutralization test and authentic viral neutralization test to detect the binding and neutralizing antibodies to SARS-CoV-2 in the vaccinees. Results We found that the antibody of seasonal HCoVs did exist before vaccination and could be boosted by SARS-CoV-2 vaccine. Further analysis demonstrated that the prior S and S1 IgG antibodies of HCoV-OC43 were positive correlated with anti-RBD and neutralization antibodies to SARS-CoV-2 at the 12 and 24 weeks post the second vaccination, and the correlation is more statistically significant at 24 weeks. The persistent antibody levels of SARS-CoV-2 were observed in vaccinees with higher pre-existing HCoV-OC43 antibodies. Conclusion Our data indicate that inactivated SARS-CoV-2 vaccination may confer cross-protection against seasonal coronaviruses in most individuals and more importantly, the pre-existing HCoV-OC43 antibody was associated with protective immunity to SARS-CoV-2, supporting the development of a pan-coronavirus vaccine.