DNA Vaccination with Genes EncodingToxoplasma gondiiAntigens GRA1, GRA7, and ROP2 Induces Partially Protective Immunity against Lethal Challenge in Mice

Abstract

C57BL/6, C3H, and BALB/c mice were vaccinated with plasmids encoding Toxoplasma gondii antigens GRA1, GRA7, and ROP2, previously described as strong inducers of immunity. Seroconversion for the relevant antigen was obtained in the majority of the animals. T. gondii lysate stimulated specific T-cell proliferation and secretion of gamma interferon (IFN-␥) 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-vaccinated C57BL/6 mice also produced IFN-␥. No interleukin-4 was detected in the supernatants of lysate-stimulated splenocytes from DNA-vaccinated mice in any of the mouse strains evaluated. As in infected animals, a high ratio of specific immunoglobulin G2a (IgG2a) to IgG1 antibodies was found in DNA-vaccinated C3H mice, suggesting that a Th1-type response had been induced. For BALB/c mice, the isotype ratio of the antibody response to DNA vaccination was less polarized. The protective potential of DNA vaccination was demonstrated in C3H mice. C3H mice vaccinated with plasmid encoding GRA1, GRA7, or ROP2 were partially protected against a lethal oral challenge with cysts of two different T. gondii strains: survival rates increased from 10% in controls to at least 70% after vaccination in one case and from 50% to at least 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 controls. 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 effect of DNA vaccination against T. gondii.

Protective Effect of Vaccination with Toxoplasma Lysate Antigen and CpG as an Adjuvant against Toxoplasma gondii in Susceptible C57BL/6 Mice

“…First, the mice used in the two studies were different. Another study reported that vaccine materials were not protective in BALB/c mice although the candidate molecules were different from our study (36). Alternatively, it is possible that BALB/c and C57BL/6 are different in sensitivity to CpG ODN because of different expression levels of TLR9 or other unknown reasons (26,30).…”

Importance of CD8 T cell-mediated immune response during intracellular parasitic infections and its implications for the development of effective vaccines

“…Although DNA immunization can elicit some degree of protective immunity, the activation of specific CD8 T cells has been poorly or not at all characterized (Nielsen et al 1999, Angus et al 2000, Vercammen et al 2000, Desolme et al 2000. Whether subunit vaccines may induce protective CD8 T cells specific for these antigen remains to be further characterized in the future.…”

Vaccines against Toxoplasma gondii: challenges and opportunities

“…Other proteins evaluated in DNA vaccines mostly originate from dense granules, rhoptries or micronemes. DNA vaccination with GRA1, GRA7 or ROP2 provided partial protection against acute and chronic infection with T. gondii 76K and IPB-G in C3H/HeN mice (Vercammen et al 2000). GRA1 partially protected against acute toxoplasmosis by generation of a cytolytic CD8 response against this antigen (Scorza et al 2003).…”