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

Le résumé fourni par la source

Whooping cough (pertussis) remains a global health problem despite widespread vaccination. Infection with Bordetella pertussis induces tissue-resident memory CD4 T cells (TRM) 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 TRM 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 TRM 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 TRM 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 TRM 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 TRM 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 TRM cells, but this can be overcome by adding the potent adjuvant LP-GMP to the aP/alum vaccine formulation.

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