DNA immunization with eukaryotic initiation factor-2α of Toxoplasma gondii induces protective immunity against acute and chronic toxoplasmosis in mice

Toxoplasma gondii infection is a serious health problem of humans and animals worldwide. T. gondii eukaryotic initiation factor-2 alpha (TgIF2 alpha) plays a crucial role in parasite viability and is an important virulence factor of T. gondii. To evaluate the vaccine potential of TgIF2 alpha, we constructed a novel eukaryotic plasmid pVAX-IF2 alpha expressing TgIF2 alpha from the RH strain and validated expression and immunogenicity in vitro in the Marc145 cell expression system by indirect immunofluorescence (IFA). Administration of pVAX-IF2 alpha intramuscularly induced specific humoral immune responses including high levels of specific TgIF2 alpha IgG antibody and a mixed IgG1/IgG2 alpha response with a predominance of IgG2 alpha production. The cellular immune response was elicited, showing significant production of IFN-gamma and IL-2 associated with Th1 type response, and thus strong cell-mediated cytotoxic activity with increased frequencies of IFN-gamma parameters analyzed in both CD4(+) and CD8(+) T cell compartments (CD4(+) IFN-gamma(+) T cells and CD8(+) IFN-gamma(+) T cells). Immunization resulted in partial protection against acute and chronic toxoplamosis in outbred Kunming mice, demonstrated by a significantly prolonged survival time (15.9 +/- 4.6 days) after challenge with the virulent RH strain and significant reduction in brain cysts (44.1%) against chronic infection with PRU cyst in contrast to control mice. Our data suggested that pVAX-IF2 alpha could be used as a DNA vaccine candidate against both acute and chronic T. gondii infection by the activation of effective humoral and cellular immune responses. (C) 2013 Elsevier Ltd. All rights reserved.