Protective immunity against Toxoplasma gondii in mice induced by the SAG2 internal image of anti-idiotype antibody

Abstract

A monoclonal antibody TGCM5 (isotype G, subclass 1, kappa light chain) against SAG2, a major surface antigen of Toxoplasma gondii tachyzoites, was produced in quantity and its Fab-containing idiotype (Id) was injected into rabbits for production of rabbit anti-Id sera. The rabbit anti-Id IgG (aId-IgG) with a SAG2 internal image was obtained by purification with a protein A column. Significant lymphocyte proliferation induced by tachyzoite lysate antigen was observed in BALB/c mice that received two injections of aId-IgG, but not in non-immunized control mice. Large amounts of gamma interferon were detected in supernatants of splenocyte cultures prepared from mice immunized with aId-IgG. Of the mice immunized with aId-IgG, 75-87.5% survived at least 28 days after a lethal challenge of 1 x 10(3) live tachyzoites, which killed all non-immunized control mice within 10 days. The results showed that the SAG2 internal image presented by aId-IgG indeed elicited a protection against the infection of T. gondii in mice.

Immunogenic characterization of the chimeric surface antigen 1 and 2 (SAG1/2) of Toxoplasma gondii expressed in the yeast Pichia pastoris

“…2b). The molecular mass of the recombinant SAG1/2 protein is slightly larger than the one expressed using E. coli (52 kDa; Yang et al 2003). The discrepancy in size between the recombinant and native (SAG1, 30 kDa and SAG2, 22 kDa) may be attributed to posttranslational modification involving glycosylation of the polypeptide backbone.…”

“…This IL-12 then activates natural killer cells and T cells to also produce interferon-γ (IFN-γ), which, along with TNF-α, produce a synergistic response and inhibit the intracellular replication of tachyzoites (Sher et al 1993). The IFN-γ response is mainly brought about by CD8+ T cells and CD4+ T cells, the former being the more proactive of the two (Thomas 2001;Yang et al 2003). In order to maintain immunity, IFN-γ has to be secreted continuously for as long as possible (Subauste and Remington 1993).…”

“…Five major surface antigens specific to the tachyzoite stage have been identified (Couvreur et al 1988), and two of them, SAG1 and SAG2, are involved in the process of host cell invasion and are highly immunogenic (Khan et al 1991;Mineo and Kasper 1994;Grimwood and Smith 1996). Recombinant SAG1, SAG2, and chimeric SAG1/2 expressed in the bacterium Escherichia coli has been shown to be effective in detecting immunoglobulin G (IgG) antibody to T. gondii in human patients with acute toxoplasmosis (Prince et al 1990;Parmley et al 1992;Yang et al 2003). Mice immunized with chimeric SAG1/2 produced by E. coli have higher survival rate (73%) after a lethal challenge of 1×10 3 live tachyzoites compared to either recombinant SAG1 (60%) or recombinant SAG2 (53%) (Yang et al 2003).…”

“…Recombinant SAG1, SAG2, and chimeric SAG1/2 expressed in the bacterium Escherichia coli has been shown to be effective in detecting immunoglobulin G (IgG) antibody to T. gondii in human patients with acute toxoplasmosis (Prince et al 1990;Parmley et al 1992;Yang et al 2003). Mice immunized with chimeric SAG1/2 produced by E. coli have higher survival rate (73%) after a lethal challenge of 1×10 3 live tachyzoites compared to either recombinant SAG1 (60%) or recombinant SAG2 (53%) (Yang et al 2003). However, mice vaccinated with E. coli-derived recombinant antigen were not fully protected against a lethal infection of T. gondii, possibly due to the incorrect folding of the recombinant protein when produced in the prokaryotic bacterial cells (Mishima et al 2001).…”

Microparticle Vaccines Against Toxoplasma gondii

“…Previous studies have shown that induction of both lymphocyte proliferation and IFN-γ production (one of Th1-type cytokines) positively correlates with protective Th1 cell-mediated immunity against T. gondii [43,44,51]. In addition, IFN-γ has been demonstrated to be a critical mediator that has to be secreted for as long as possible in order to maintain anti Toxoplasma immunity [52,53].…”