Mucosal Immunization with DTaP Confers Protection against Bordetella pertussis Infection and Cough in Sprague-Dawley Rats

Abstract

Pertussis is a respiratory disease caused by the Gram-negative pathogen, Bordetella pertussis (Bp). The transition from a whole cell pertussis vaccine (wP; DTP) to an acellular pertussis vaccine (aP; DTaP; Tdap) correlates with an increase in pertussis cases, despite widespread vaccine implementation and coverage, and it is now appreciated that the protection provided by aP rapidly wanes. To recapitulate the localized immunity observed from natural infection, mucosal vaccination with aP was explored using the coughing rat model of pertussis. Overall, our goal was to evaluate the route of vaccination in the coughing rat model of pertussis. Immunity induced by both oral gavage (OG) and intranasal (IN) vaccination of aP in Bp challenged rats over a nine-day infection was compared to intramuscular (IM)-wP and IM-aP immunized rats that were used as positive controls. Our data demonstrate that mucosal immunization of aP resulted in production of anti-Bp IgG antibody titers similar to IM-wP and IM-aP vaccinated controls post-challenge. IN-aP also induced anti-Bp IgA antibodies in the nasal cavity. Immunization with IM-wP, IM-aP, IN-aP, and OG-aP immunization protected against Bp induced cough, while OG-aP immunization did not protect against respiratory distress. Mucosal immunization by both IN and OG administration protected against acute inflammation and decreased bacterial burden in the lung compared to mock vaccinated challenge (MVC) rats. The data presented in this study suggests that mucosal vaccination with aP can induce a mucosal immune response and provide protection against Bp challenge. This study highlights the potential benefits and uses of the coughing rat model of pertussis; however, further questions regarding waning immunity still require additional investigation.