Citation

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,
macrophage and 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.