TH17 responses elicited by a BcfA-containing vaccine protects against B. bronchiseptica disease and respiratory tract bacterial burden in mice 2257134

Abstract

Abstract Introduction Bordetella bronchiseptica (Bb) is a respiratory pathogen of farm and companion animals. Current vaccines do not prevent transmission. Improved vaccines are needed to address this problem. We tested an intranasal subunit vaccine containing Bordetella colonization factor A (BcfA), filamentous hemagglutinin (FHA), and pertactin (Prn) as antigens. BcfA, an outer membrane protein with dual antigen and adjuvant functions, promotes a protective TH1/TH17 immune response critical for clearance of Bordetella species. Methods Mice were primed and boosted intranasally with BcfA/FHA/Prn. Immune responses were evaluated 2 weeks post boost by flow cytometry and ELISAs. Immunized animals were challenged with the laboratory Bb strain RB50, and phagocytes and CFUs were analyzed at days 4, 7, 14, and 28 post-challenge. Respiratory function was evaluated using noninvasive whole-body plethysmography. Results The vaccine elicited mucosal CD4+IL-17+ tissue resident memory T cells and systemic and mucosal IgG and IgA responses. Unimmunized challenged mice showed increased coughing and impaired lung function while BcfA/FHA/Prn immunized mice were protected from respiratory disease and showed reduced bacterial burden in the lungs and nose. Conclusion These findings demonstrate that an intranasal subunit vaccine containing BcfA/FHA/Prn elicits mucosal and systemic immunity and has the potential to provide sustained protection against Bb infection and disease and reduce colonization and subsequent transmission. Funding Source RO1AI153829 Topic Categories Vaccines and Immunotherapy (VAC)