Longitudinal adaptive immune profiling of vaccinated children reveals correlates of protection against symptomatic SARS-CoV-2 infection

Abstract The development of evidence-based COVID-19 vaccination policies for new birth cohorts is hindered by the lack of systematic examination of the protective capacity of elements of adaptive immunity besides neutralising antibodies. To address this knowledge gap, we conducted a longitudinal cohort study of healthy 5- to 12-year-olds vaccinated with BNT162b2. We serially measured binding and neutralising antibody titres, Spike (S)-specific memory B cell (MBC) and S-reactive T cell responses over 1 year; SARS-CoV-2 infections were ascertained using antigen rapid tests, and serological and cellular responses against nucleocapsid. We found that children mounted antibody, MBC and T cell responses after 2 doses, with continual expansion of SARS-CoV-2 variant neutralising capacity up to 1 year in the absence of wild-type infection. A booster (third) dose only improved neutralising antibody titres without impacting MBC and T cell responses. Hybrid immunity was greater in those infected after 2 vaccine doses than those infected before dose 2. Binding IgG titres, MBC and T cell responses were predictive of protection against symptomatic infection prior to attaining hybrid immunity; neutralising antibody titres only correlated with protection after hybrid immunity. The stable MBC and T cell responses over time suggest sustained protection against symptomatic SARS-CoV-2 infection, even when antibody levels wane.