A natural adjuvant underlies vaccine response variability in humans 4172

Abstract Description The antibody titer induced by a vaccine varies substantially among humans. We hypothesize that the pre-vaccination (VAX) serum abundances of certain cytokines may regulate the response. We pooled data (cytokine N = 66) from 5 different flu vaccine cohorts in 5 seasons (sample N = 664, received Inactivated Influenza Vaccine/IIV). The analysis finds that the age-associated decrease of antibody response is only significant in subjects with low-level pre-VAX flu antibodies (sample N = 353). In this group, the meta-analysis identifies a significant correlation between baseline/Day 0 serum IFN-β concentration and the antibody response on Day 28. Beyond correlation, we examined the vaccine-adjuvant functionality of cytokines in spleen organoids derived from organ transplant donors. Notably, Type I interferons are not stimulated by the inactivated vaccine. In contrast, Live Attenuated Influenza Vaccine (LAIV) can stimulate a potent Type I interferon and antibody response. Supplementing a single cytokine, IFN-β, can recapitulate most of the live vaccine-specific induction of numerous other cytokines and rescue the antibody induction deficiency of the inactivated vaccine. Organoid-based screen identifies other cytokines capable of adjuvating the inactivated vaccine, including Type I IFNs (α, ω), IL-10, IL21, IL12, and IL9. In contrast, many cytokines (notably, type II IFN, γ) strongly induced by the IIV could not adjuvate the antibody responses. Funding Sources NIH Life Science Research Foundation HHMI SU2C Topic Categories Immune Mechanisms of Human Disease (HUM)