Article

Induction of protective immunity against toxoplasmosis in mice by DNA immunization with a plasmid encoding Toxoplasma gondii GRA4 gene

Equipe Associée INRA d’Immunologie Parasitaire, Faculté des Sciences Pharmaceutiques, 31 Ave. Monge, 37200 Tours, France
Vaccine DOI:10.1016/S0264-410X(00)00035-9 pp.2512-2521

ABSTRACT GRA4 is a dense granule protein of Toxoplasma gondii that is a candidate for vaccination against this parasite. We have inserted the entire coding sequence of GRA4 into an eukaryotic expression vector to determine whether DNA immunization can elicit protective immune response to T. gondii. Susceptible C57BL/6 mice were then vaccinated intramuscularly with GRA4 DNA and orally challenged with a lethal dose of 76 K T. gondii strain cysts. Immunization with pGRA4 resulted in a 62% survival of C57BL/6 infected mice. Mice immunized with GRA4 DNA developed high levels of serum anti-GRA4 immunoglobulin G antibodies as well as a cellular immune response, as assessed by splenocyte proliferation, in response to recombinant GRA4 protein restimulation in vitro. The cellular immune response was associated with IFN-γ and IL-10 synthesis, suggesting a modulated Th1-type response. Splenocyte proliferation was strongly enhanced and protection slightly higher by inoculation with GRA4 DNA combined with a granulocyte-macrophage colony-stimulating factor expressing vector. This is the first report that demonstrates the establishment of a DNA vaccine-induced protective immunity against the acute phase of T. gondii infection.

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Keywords

76 K T. gondii strain cysts
 
acute phase
 
cellular immune response
 
dense granule protein
 
DNA vaccine-induced protective immunity
 
entire coding sequence
 
first report
 
GRA4
 
GRA4 DNA
 
IL-10 synthesis
 
intramuscularly
 
mice
 
Mice immunized
 
modulated Th1-type response
 
pGRA4
 
recombinant GRA4 protein restimulation
 
serum anti-GRA4 immunoglobulin G antibodies
 
splenocyte proliferation
 
Susceptible C57BL/6 mice
 
T. gondii infection