DNA vaccination with genes encoding Toxoplasma gondii antigens GRA1, GRA7,and ROP2 induces partially protective immunity against lethal challenge inmice

C57BL/6, C3H, and BALB/c mice were vaccinated,vith plasmids encoding Toxopl asma gondii antigens GRA1, GRA7, and ROP2, previously described as strong i nducers of immunity. Seroconversion for the relevant antigen,vas obtained i n the majority of the animals. T. gondii lysate stimulated specific T-cell proliferation and secretion of gamma interferon (IFN-gamma) in spleen cell cultures from vaccinated BALB/c and C3H mice but not in those from control mice. Although not proliferating, stimulated splenocytes from DNA-vaccinate d C57BL/6 mice also produced IFN-gamma. No interleukin-4 was detected in th e supernatants of lysate-stimulated splenocytes from DNA-vaccinated mice in any of the mouse strains evaluated. As in infected animals, a high ratio o f specific immunoglobulin G2a (IgG2a) to IgG1 antibodies was found in DNA-v accinated C3H mice, suggesting that a Th1-type response had been induced. F or BALB/c mice, the isotype ratio of the antibody response to DNA vaccinati on was less polarized, The protective potential of DNA vaccination was demo nstrated in C3H mice. C3H mice vaccinated with plasmid encoding GRA1, GRA7, or ROP2 were partially protected against a lethal oral challenge with cyst s of two different T,gondii strains: survival rates increased from 10% in c ontrols to at least 70% after vaccination in one case and from 50% to at le ast 90% in the other. In vaccinated C3H mice challenged with a nonlethal T. gondii dose, the number of brain cysts was significantly lower than in con trols. DNA vaccination did not protect BALB/c or C57BL/6 mice. Our results demonstrate for the first time in an animal model a partially protective ef fect of DNA vaccination against T. gondii.