Parenteral immunization of mice with a genetically inactivated pertussis toxin DNA vaccine induces cell-mediated immunity and protection.
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-gamma) 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-gamma 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.
Fry
Scott R
SR
Department of Biological and Physical Sciences, University of Southern Queensland, Toowoomba 4350, Queensland, Australia.
Chen
Austen Y
AY
Department of Biological and Physical Sciences, University of Southern Queensland, Toowoomba 4350, Queensland, Australia.
Daggard
Grant
G
Department of Biological and Physical Sciences, University of Southern Queensland, Toowoomba 4350, Queensland, Australia.
Mukkur
Trilochan K S
TKS
Department of Biological and Physical Sciences, University of Southern Queensland, Toowoomba 4350, Queensland, Australia.
D000818:Animals; D000917:Antibody Formation; D007111:Immunity, Cellular; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D037342:Pertussis Toxin / Q000235:genetics* / Q000276:immunology; D010567:Pertussis Vaccine / Q000008:administration & dosage* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D014917:Whooping Cough / Q000276:immunology / Q000517:prevention & control*
D007376:Interleukin-2; D010567:Pertussis Vaccine; D019444:Vaccines, DNA; D015164:Vaccines, Inactivated; D007371:Interferon-gamma; D037342:Pertussis Toxin