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

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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.

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