Dynamic impact of bivalent COVID-19 vaccine boosters on systemic and mucosal antibody and T cell immunity

COVID-19 vaccines were updated to address immune escape from variants of concern (VOC). We explored the impact of ancestral/BA.1 bivalent mRNA booster vaccination (Autumn 2022) on peripheral and nasal antibody and T-cell responses to SARS-CoV-2 in an observational cohort of 133 healthcare workers, building on previous longitudinal vaccination studies. We demonstrate that maintenance of antibody and T-cell responses up to eighteen months following the third vaccine is at least partially driven by intercurrent infection. Boosting with the bivalent vaccine increases the breadth of circulating and nasal antibodies to spike, which waned over time but was still detectable six months post-dose. T-cell responses are well maintained and highly cross-reactive to VOCs irrespective of booster vaccination. Vaccination strongly boosted nasal IgG, but this was short-lived compared to circulating antibodies. Overall, ongoing COVID-19 vaccination provides benefit, boosting immunity in individuals who have not been recently infected, but new strategies may be needed to provide longer-term nasal immunity.