BscF from Bordetella pertussis provides advantageous adjuvant activity when paired with the acellular pertussis vaccine: enhanced Th1/Th17 pertussis-specific immune response

Abstract

Abstract Incidence of pertussis, a severe respiratory disease caused by Bordetella pertussis, have been on the rise. This resurgence has been linked to antigenic divergence in circulating pertussis strains as well as waning or ineffective immunity induced by the current acellular pertussis (aP) vaccine. The current aP vaccine replaced a whole cell pertussis (wP) vaccine in the 1990s due to adverse events associated with the wP vaccine. Alum-absorbed aP vaccine has been shown to elicit a strong antibody response and considerable Th2 type CD4+ T cells. In contrast, wP vaccine promotes Th1/Th17 type cellular immunity and associated opsonizing antibodies presumably via its PAMPs. We have previously demonstrated that BscF, a B. pertussis needle protein, acts as a strong TLR agonist. Here we characterized the contribution of BscF to a laboratory prepared aP vaccine-induced response. aP + BscF resulted in statistically greater pertussis-specific antibody titers, compared to sham aP + PBS. BscF enhanced long-term aP-specific immunity, compared to either the alum or sham controls, as measured by increased numbers of central memory T cells. Moreover, the addition of BscF resulted in skewing the pertussis-specific immunity toward Th1 and Th17 responses, compared to the addition of alum or PBS which skewed pertussis-specific immunity away from Th1/Th17 responses. Mice immunized with aP + BscF demonstrated significantly reduced bacterial burden in their lungs 5 dpi. These findings suggest that BscF induced a strong Th1 and Th17 anti-pertussis response, potentially may provide protective BscF-specific immunity, and could be a novel additional component in the next generation aP vaccine.