Parenteral immunization of mice with a genetically inactivated pertussis toxin DNA vaccine induces cell-mediated immunity and protection

Department of Biological and Physical Sciences, University of Southern Queensland, Toowoomba 4350, Queensland, Australia Correspondence Trilochan K. S. Mukkur tk_mukkur{at}hotmail.com Received 23 July 2007 Accepted 13 September 2007 The immunogenicity and protective efficacy of a DNA vaccine encoding a genetically inactivated S1 domain of pertussis toxin was evaluated using a murine respiratory challenge model of Bordetella pertussis infection. It was found that mice immunized via the intramuscular route elicited a purely cell-mediated immune response to the DNA vaccine, with high levels of gamma interferon (IFN- ) and interleukin (IL)-2 detected in the S1-stimulated splenocyte supernatants and no serum IgG. Despite the lack of an antibody response, the lungs of DNA-immunized mice were cleared of B. pertussis at a significantly faster rate compared with mock-immunized mice following an aerosol challenge. To gauge the true potential of this S1 DNA vaccine, the immune response and protective efficacy of the commercial diphtheria–tetanus–acellular pertussis (DTaP) vaccine were included as the gold standard. Immunization with DTaP elicited a typically strong T-helper (Th)2-polarized immune response with significantly higher titres of serum IgG than in the DNA vaccine group, but a relatively weak Th1 response with low levels of IFN- and IL-2 detected in the supernatants of antigen-stimulated splenocytes. DTaP-immunized mice cleared the aerosol challenge more efficiently than DNA-immunized mice, with no detectable pathogen after day 7 post-challenge. Abbreviations: aP, acellular pertussis; CHO, Chinese hamster ovary; CMI, cell-mediated immunity; ConA, concanavalin A; DTaP, diphtheria–tetanus–acellular pertussis; HRP, horseradish peroxidase; i.d., intradermal; IFN- , gamma interferon; IL, interleukin; i.m., intramuscular; IMAC, immobilized metal affinity chromatography; i.n., intranasal; i.p., intraperitoneal; PT, pertussis toxin; s.c., subcutaneous; Th, T-helper; wP, whole-cell pertussis. Present address: Panbio Limited, Brisbane, Queensland, Australia.