IL-10 induced by alum-adjuvanted acellular pertussis vaccine reduces its capacity to induce protective respiratory tissue-resident CD4 T cells

Whooping cough (pertussis) remains a global health problem despite widespread vaccination. Infection with Bordetella pertussis induces tissue-resident memory CD4 T cells (T_RM) with Th1/Th17 phenotype, which confer protective immunity against re-infection. Current alum-adjuvanted acellular pertussis (aP) vaccines (aP/alum) protect against lung infection but induce limited cellular immunity or expansion of respiratory T_RM cells and fail to prevent infection of the nasal mucosa or bacterial transmission. This study aims to elucidate the mechanisms by which aP/alum vaccines fail to recruit T_RM cells to the nasal tissue and how novel adjuvants may overcome this deficit. Immunization of mice with aP/alum vaccine induced antibody responses but failed to induce systemic Th1 or Th17 responses and T_RM cells in nasal tissue after B. pertussis challenge. In contrast, immunization of mice with aP/alum vaccine induced IL-10 production in draining lymph nodes. Immunization of IL-10-deficient mice with an aP/alum vaccine promoted induction of respiratory IFN-γ and IL-17-secreting T_RM cells and conferred protection against B. pertussis infection of the nasal cavity. Substitution or adding a novel adjuvant LP-GMP, comprising TLR2 and STING agonists, to an aP vaccine generated respiratory T_RM cells and promoted bacterial clearance from the nasal mucosa. These findings suggest that IL-10 may play a role in the failure of aP/alum vaccines to protect against B. pertussis infection of the nasal mucosa by suppressing activation and recruitment of T_RM cells, but this can be overcome by adding the potent adjuvant LP-GMP to the aP/alum vaccine formulation.