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.
To 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.
Mévélec
Marie-Noëlle
MN
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@univ-tours.fr
Bout
Daniel
D
Desolme
Benoît
B
Marchand
Hervé
H
Magné
Rémy
R
Bruneel
Odile
O
Buzoni-Gatel
Dominique
D
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics* / Q000276:immunology; D001835:Body Weight; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology; D016052:Protozoan Vaccines / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000517:prevention & control*; D014125:Toxoplasmosis, Congenital / Q000517:prevention & control*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
D000953:Antigens, Protozoan; C079248:GRA4 protein, Toxoplasma gondii; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; C047168:SAG1 antigen, Toxoplasma; D019444:Vaccines, DNA; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor