Intranasal acellular pertussis vaccine provides mucosal immunity and protects mice from Bordetella pertussis

Current acellular pertussis vaccines fall short of optimal protection against the human respiratory pathogen Bordetella pertussis resulting in increased incidence of a previously controlled vaccine- preventable disease. Natural infection is known to induce a protective mucosal immunity. Therefore, in this study, we aimed to use acellular pertussis vaccines to recapitulate these mucosal immune responses. We utilized a murine immunization and challenge model to characterize the efficacy of intranasal immunization (IN) with DTaP vaccine or DTaP vaccine supplemented with curdlan, a known Th1/Th17 promoting adjuvant. Protection from IN delivered DTaP was compared to protection mediated by intraperitoneal injection of DTaP and whole-cell pertussis vaccines. We tracked fluorescently labeled DTaP after immunization and detected that DTaP localized preferentially in the lungs while DTaP with curdlan was predominantly in the nasal turbinates. IN immunization with DTaP, with or without curdlan adjuvant, resulted in anti- B. pertussis and anti-pertussis toxin IgG titers at the same level as intraperitoneally administered DTaP. IN immunization was able to protect against B. pertussis challenge and we observed decreased pulmonary pro-inflammatory cytokines, neutrophil infiltrates in the lung, and bacterial burden in the upper and lower respiratory tract at day 3 post challenge. Furthermore, IN immunization with DTaP triggered mucosal immune responses such as production of B. pertussis -specific IgA, and increased IL-17A. Together, the induction of a mucosal immune response and humoral antibody-mediated protection associated with an IN administered DTaP and curdlan adjuvant warrant further exploration as a pertussis vaccine candidate formulation. Bordetella pertussis : mimicking the mucosal response for protection An acellular pertussis vaccine is used to protect against whooping cough, caused by the bacterial pathogen Bordetella pertussis ; however, there is a growing number of pertussis cases despite vaccination. Here Dylan Boehm and colleagues combine the acellular vaccine with a pro-inflammatory adjuvant to maximise the mucosal immune response when administered intra-nasally in a murine model. They use curdlan, a 1,3 β-glucan, which is known for its Th1/Th17 promoting abilities. Intra-nasal vaccination with curdlan resulted in protection that was comparable to typical intra-peritoneal administration or whole-cell pertussis vaccines, with similar IgG levels against th