Cross-reactive antibodies after SARS-CoV-2 infection and vaccination

Grobben, M.; van der Straten, K.; Brouwer, P. J. M.; Brinkkemper, M.; Maisonnasse, P.; Dereuddre-Bosquet, N.; Burger, J. A.; Poniman, M.; Oomen, M.; Eggink, D.; Bijl, T. P. L.; van Willigen, H. D. G.; Wynberg, E.; Verkaik, B. J.; Figaroa, O. J. A.; de Vries, P. J.; Boertien, T. M.; Le Grand, R.; de Jong, M. D.; Prins, M.; Chung, A. W.; de Bree, G. J.; Sanders, R. W.; van Gils, M. J.

Current SARS-CoV-2 vaccines are losing efficacy against emerging variants and may not protect against future novel coronavirus outbreaks, emphasizing the need for more broadly protective vaccines. To inform the development of a pan-coronavirus vaccine, we investigated the presence and specificity of cross-reactive antibodies against the spike (S) proteins of human coronaviruses (hCoV) after SARS-CoV-2 infection and vaccination. We found an 11 to 123-fold increase in antibodies binding to SARS-CoV and MERS-CoV as well as a 2 to 4-fold difference in antibodies binding to seasonal hCoVs in COVID-19 convalescent sera compared to pre-pandemic healthy donors, with the S2 subdomain of the S protein being the main target for cross-reactivity. In addition, we detected cross-reactive antibodies to all hCoV S proteins after SARS-CoV-2 S protein immunization in macaques, with higher responses for hCoV more closely related to SARS-CoV-2. These findings support the feasibility of and provide guidance for development of a pan-coronavirus vaccine.