Vaccine-breakthrough infection by the SARS-CoV-2 Omicron variant elicits broadly cross-reactive immune responses

Highly transmissible SARS-CoV-2 Omicron variant has posted a new crisis for COVID-19 pandemic control. Within a month, Omicron is dominating over Delta variant in several countries probably due to immune evasion. It remains unclear whether vaccine-induced memory responses can be recalled by Omicron infection. Here, we investigated host immune responses in the first vaccine-breakthrough case of Omicron infection in Hong Kong. We found that the breakthrough infection rapidly recruited potent cross-reactive broad neutralizing antibodies (bNAbs) against current VOCs, including Alpha, Beta, Gamma, Delta and Omicron, from unmeasurable IC50 values to mean 1:2929 at around 9-12 days, which were higher than the mean peak IC50 values of BioNTech-vaccinees. Cross-reactive spike- and nucleocapsid-specific CD4 and CD8 T cell responses were detected. Similar results were also obtained in the second vaccine-breakthrough case of Omicron infection. Our preliminary findings may have timely implications to booster vaccine optimization and preventive strategies of pandemic control.

Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections

The World Health Organization has recently declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, as pandemic. There is currently a lack of knowledge in the antibody response elicited from SARS-CoV-2 infection. One major immunological question is concerning the antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by using plasma from patients infected by SARS-CoV-2 or SARS-CoV, and plasma obtained from infected or immunized mice. Our results show that while cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses is rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. Whether these non-neutralizing antibody responses will lead to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding the antigenicity differences between SARS-CoV-2 and SARS-CoV, but also has important implications in vaccine development.