Impact of dose on norovirus antibody kinetics following infection or vaccination

BACKGROUND: Noroviruses are a leading cause of acute gastroenteritis worldwide, yet no licensed vaccines currently exist. Antibody-mediated immunity provides protection, but the relationship between norovirus exposure dose and antibody kinetics remains unclear. METHODS: We analyzed longitudinal data on histo-blood group antigen (HBGA)-blocking, IgA, and IgG antibodies from a human norovirus infection trial and a candidate vaccine trial. We developed hierarchical nonlinear Bayesian models to characterize antibody kinetics following different amounts of virus or vaccine antigen exposure within infection and vaccination settings. We fit models with exponential and power-law decay terms and compared their performance. RESULTS: Across studies and antibody types, the amount of antigen individuals were exposed to influenced early antibody kinetics, including growth, peak, and decay, but effects differed between infection and vaccination. Doses that produced larger initial antibody boosts also decayed faster, resulting in little association with one-year antibody persistence. CONCLUSIONS: Our findings suggest that amount and type of antigen exposure shapes early antibody kinetics but not lasting durability. This reflects a trade-off between dose-induced initial immune boost and subsequent waning.