BPZE1 vaccination induces IL-17+ and IL-22+ CD4+ T cells associated with nasal mucosal secretory IgA responses in humans: effects on virulent Bordetella pertussis colonisation

Abstract Pertussis remains a major public health challenge due to the inability of current acellular vaccines to prevent Bordetella pertussis colonisation and transmission. The live-attenuated intranasal vaccine, BPZE1, has shown efficacy in protecting against infection following challenge with virulent B. pertussis, but the immune mechanisms underpinning this protective effect are poorly defined. In this study, we demonstrate that intranasal vaccination with BPZE1 induced circulating CD4 + T cells of Th17 and Th22 effector phenotype. These responses correlated positively with BPZE1-induced secretory IgA (SIgA) responses, suggesting coordinated induction of mucosal immunity. Among BPZE1 recipients who developed breakthrough infection following virulent B. pertussis challenge, higher vaccine-induced SIgA titres were significantly associated with reduced colonisation density. By contrast, BPZE1-induced serum IgA and IgG titres were not associated with reduced colonisation density. These findings identify a Th17/Th22-SIgA immune axis as a feature of BPZE1 vaccination and support the hypothesis that BPZE1-induced SIgA may contribute to reduced B. pertussis colonisation density in participants with virulent B. pertussis breakthrough infection despite BPZE1 vaccination.