Vaccine potential of antigen cocktails composed of recombinant Toxoplasma gondii TgPI-1, ROP2 and GRA4 proteins against chronic toxoplasmosis in C3H mice

PICCHIO, MARIANO S.; SÁNCHEZ, VANESA R.; ARCON, NADIA; SOTO, ARIADNA S.; PERRONE SIBILIA, MATÍAS; ALDIRICO, MARÍA DE LOS ANGELES; URRUTIA, MARIELA; MORETTA, ROSALÍA; FENOY, IGNACIO M.; GOLDMAN, ALEJANDRA; MARTIN, VALENTINA

EXPERIMENTAL PARASITOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2018 vol. 185 p. 62 - 70

0014-4894

The development of an effective and safe vaccine to prevent Toxoplasma gondii infection is an importantaim due to the great clinical and economic impact of this parasitosis. We have previously demonstratedthat immunization with the serine protease inhibitor-1 (TgPI-1) confers partial protection to C3H/HeNand C57BL/6 mice. In order to improve the level of protection, in this work, we combined this novelantigen with ROP2 and/or GRA4 recombinant proteins (rTgPI-1þrROP2, rTgPI-1þrGRA4, rTgPI-1þrROP2þrGRA4) to explore the best combination against chronic toxoplasmosis in C3H/HeN mice. Alltested vaccine formulations, administered following a homologous prime-boost protocol that combinesintradermal and intranasal routes, conferred partial protection as measured by the reduction of braincyst burden following oral challenge with tissue cysts of Me49 T. gondii strain. The highest level ofprotection was achieved by the mixture of rTgPI-1 and rROP2 proteins with an average parasite burdenreduction of 50% compared to the unvaccinated control group. The vaccine-induced protective effect wasrelated to the elicitation of systemic cellular and humoral immune responses that included antigenspecificspleen cell proliferation, the release of Th1/Th2 cytokines, and the generation of antigenspecificantibodies in serum. Additionally, mucosal immune responses were also induced,characterized by secretion of antigen-specific IgA antibodies in intestinal lavages and specific mesentericlymph node cell proliferation. Our results demonstrate that rTgPI-1þrROP2 antigens seem a promisingmixture to be combined with other immunogenic proteins in a multiantigenic vaccine formulationagainst toxoplasmosis.