Bivalent mRNA booster vaccination recalls cellular and antibody immunity against antigenically divergent SARS-CoV-2...

The ongoing rollout of SARS-CoV-2 vaccines lags behind rapid viral evolution. Updated vaccine immunogens elicit neutralising antibodies against the component strain. However, protection against future SARS-CoV-2 variants is unclear. Here, we sought to understand factors underpinning serological breadth following bivalent BA.1 vaccination. Booster vaccination of 33 individuals elicited robust and durable antibody responses against component vaccine antigens and elevated frequencies of spike-specific CD4 and CD8 T cells. Immunisation predominantly drove recall of cross-reactive memory B cells which also recognised XBB.1.5 spike, with significantly enhanced neutralisation titres against XBB virus seen within 91% of participants. Multivariate regression indicated that both baseline neutralising titres and spike-specific CD4 T cell frequencies were strong predictors of ancestral, BA.1 and XBB neutralisation post-immunisation. These data highlight that updated SARS-CoV-2 vaccines recall cross-reactive memory that maintains recognition of antigenically evolved viral variants and suggests T cell help and prior antibody titres underpin robust vaccine-induced neutralising activity.