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Evaluation of protective effect of DNA vaccination with genes encoding antigens GRA4 and SAG1 associated with GM-CSF plasmid, against acute, chronical and congenital toxoplasmosis in mice.

AbstractTo develop a multiantigenic vaccine against toxoplasmosis, two Toxoplasma gondii antigens, SAG1 and GRA4 selected on the basis of previous immunological and immunization studies, were chosen. We showed that DNA-based immunization with plasmids expressing GRA4 (pGRA4) or SAG1 (pSAG1mut) reduced mortality of susceptible C57BL/6 mice upon oral challenge with cysts of the 76K type II strain (62% survival). Immunization with pGRA4 and pSAG1mut, enhanced the protection (75% survival). This protection was further increased by co-inoculation with a plasmid encoding the granulocyte-macrophage colony-stimulating factor (GM-CSF) (87% survival). This latter DNA cocktail provided significant protection of less susceptible outbred Swiss OF1 mice against the development of cerebral cysts. A significantly higher survival of newborns from immunized outbred mice exposed to infection during gestation was observed (4.25+/-3.77 live pups/litter) in comparison to non-immunized mice (1.08+/-2.15 live pups/litter) without preventing parasite vertical transmission. Analysis of the immune response showed that protected animals developed a specific humoral and cellular Th1 response to native T. gondii SAG1 and GRA4 antigens. Our data demonstrated that protection was improved by associating antigens (SAG1 and GRA4) and cytokine (GM-CSF) for further development of a multiantigenic vaccine against toxoplasmosis.
AuthorsMarie-Noëlle Mévélec, Daniel Bout, Benoît Desolme, Hervé Marchand, Rémy Magné, Odile Bruneel, Dominique Buzoni-Gatel (Affiliation: Université François-Rabelais de Tours, INRA, UMR 483 Université-INRA d'Immunologie Parasitaire et Vaccinologie, IFR Agents transmissibles et Infectiologie, UFR des Sciences Pharmaceutiques, 31 Avenue Monge, 37200 Tours, France. mevelec at univ-tours.fr)
JournalVaccine (Vaccine) Vol. 23 Issue 36 Pg. 4489-99 (Aug 22 2005) ISSN: 0264-410X Netherlands
PMID15935521 (Publication Type: Journal Article)
Chemical References
  • Antigens, Protozoan
  • GRA4 protein, Toxoplasma gondii
  • Protozoan Proteins
  • Protozoan Vaccines
  • SAG1 antigen, Toxoplasma
  • Vaccines, DNA
  • Interleukin-4
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor
Topics
  • Animals
  • Antigens, Protozoan (genetics, immunology)
  • Body Weight
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor (genetics)
  • Interferon-gamma (biosynthesis)
  • Interleukin-4 (biosynthesis)
  • Mice
  • Mice, Inbred C57BL
  • Plasmids
  • Protozoan Proteins (genetics, immunology)
  • Protozoan Vaccines (immunology)
  • Toxoplasma (immunology)
  • Toxoplasmosis, Animal (prevention & control)
  • Toxoplasmosis, Congenital (prevention & control)
  • Vaccination
  • Vaccines, DNA (immunology)