Impact of hybrid immunity booster vaccination and Omicron breakthrough infection on SARS-CoV-2 VOCs cross-neutralization

The elicitation of cross-variant neutralizing antibodies against SARS-CoV-2 represents a major goal for current COVID-19 vaccine strategies. Additionally, natural infection may also contribute to broaden neutralizing responses. To assess the contribution of vaccines and natural infection, we cross-sectionally analyzed plasma neutralization titers of six groups of individuals, organized according to the number of vaccines they received and their SARS-CoV-2 infection history. Two doses of vaccine had a limited capacity to generate cross-neutralizing antibodies against Omicron variants of concern (VOCs) in uninfected individuals, but efficiently synergized with previous natural immunization in convalescent individuals. In contrast, booster dose had a critical impact on broadening the cross-neutralizing response in uninfected individuals, to level similar to hybrid immunity, while still improving cross-neutralizing responses in convalescent individuals. Omicron breakthrough infection improved cross-neutralization of Omicron subvariants in non-previously infected vaccinated individuals. Therefore, ancestral Spike-based immunization, via infection or vaccination, contributes to broaden SARS-CoV-2 humoral immunity.

Automated summary

The development of cross-variant neutralizing antibodies against SARS-CoV-2 is an important goal for COVID-19 vaccine strategies. This study analyzed the neutralization titers of plasma from different groups based on vaccine doses and infection history. Two doses of vaccine had limited efficacy in generating cross-neutralizing antibodies against Omicron variants in uninfected individuals, but showed synergy with natural immunization in convalescent individuals. Booster doses significantly broadened the cross-neutralizing response in uninfected individuals and improved responses in convalescent individuals. Omicron breakthrough infections also improved cross-neutralization in vaccinated individuals. Overall, ancestral Spike-based immunization, through infection or vaccination, helps broaden SARS-CoV-2 humoral immunity.