The immunogenicity and protective efficacy of systemically and orally delivered pertussis antigens entrapped in either microparticle poly-lactide-co-glycolide (PLG) or nanoparticle PLG formulations were evaluated in a murine respiratory challenge model for infection with Bordetella pertussis. The results demonstrate that immunization with two parenteral doses of 1 microg or three oral doses of 100 microg of pertussis toxoid (PTd) and filamentous haemagglutinin (FHA) encapsulated in PLG conferred a high level of protection against B. pertussis challenge. Furthermore protection could be generated with a single parenteral immunization with a combined microparticle and nanoparticle formulation. However, the route of immunization and the size of the particles affected the type of T cell response induced. Parenteral immunization with PTd and FHA entrapped in PLG microparticles elicits a potent type 1 T cell response and potent antibody response when given by the intraperitoneal (i.p.) or intramuscular (i.m.) route. In contrast, nanoparticle formulations favoured the induction of Th2 cells.