Nasal immunization with compound 48/80-adjuvanted acellular pertussis vaccines is an effective strategy to induce pertussis-specific systemic and mucosal immunity.

PURPOSE: Mast cell activating adjuvants induce vaccine-specific systemic and mucosal immunity when administered intranasally. Bordetella pertussis infects the respiratory tract and caused 0.45% childhood mortality in the United States before implementing pertussis vaccines. Pertussis infections are resurging. Immunity induced by current pertussis vaccines wanes quickly, possibly due to vaccine-induced T helper (Th) 2 and weak mucosal immunity. B. pertussis induces Th1, Th17, and mucosal immunoglobulin A (IgA) immunity, providing durable protection against disease. Next-generation pertussis vaccines that induce Th1, Th17, and IgA immunity may reduce the resurgence of pertussis. This study determined if nasal pertussis vaccines adjuvanted with the mast cell activator compound 48/80 (C48/80) modulate pertussis-specific immunity. MATERIALS AND METHODS: Mice received intranasal C48/80-adjuvanted pertussis vaccines or subcutaneous aluminum-adjuvanted pertussis vaccines. Immunized mice were challenged with B. pertussis and monitored for protection against infection. Pertussis-specific immune profiles were characterized after immunization. A C48/80 and CpG adjuvant combination was evaluated to enhance pertussis-specific Th1 immunity. RESULTS: Alum-adjuvanted pertussis vaccines induce Th2 immunity and undetectable IgA responses. Nasal C48/80-adjuvanted pertussis vaccines enhance pertussis-specific serum and mucosal IgA and Th2 and Th17 responses but not Th1 immunity. The C48/80 and CpG adjuvant combination enhances systemic and mucosal pertussis-specific Th1, Th17, and IgA compared to unadjuvanted pertussis vaccines, which may be the desired immune response to protect against pertussis infections. CONCLUSION: We demonstrate that nasal pertussis vaccines containing C48/80 adjuvants induce pertussis-specific IgA, Th1-, and Th17-associated immunity when combined with CpG, which may be an effective strategy to improve pertussis vaccines.