The TLR agonist profilin protein from Toxoplasma gondii enhance immunity against GRA7 protein in mice

NADIA ARCON, MARIANO S. PICCHIO, IGNACIO M. FENOY, MATÍAS D. PERRONE SIBILIA, ARIADNA S. SOTO, VANESA R. SÁNCHEZ, MARÍA DE LOS ÁNGELES ALDIRICO, ALEJANDRA GOLDMAN, VALENTINA MARTIN.

Congreso; Recunión Anual de la Sociedad Argentina de Inmunología; 2016

The development of vaccines against T. gondii infection is a high priority, given the high rate of infection close to 30% of theworld population. The only commercialvaccine is based on live attenuated parasitesused in sheep to prevent abortions induced by congenital toxoplasmosis. TLR ligands are attractive adjuvant candidates in vaccinedevelopment. T. gondii profilin(TgPF), is a protein involved in parasite motility and is recognized by TLR-5, -11and -12 receptors of the innate immune system. Activation of these receptorsresults in the expression of IL-12, cytokine involved in the differentiation ofnaive T cells towards a Th1phenotype, immune response profile associated with protection against infectionby this parasite. The aim of the present work was to study the immunogenicity ofa vaccine formulation containing a recombinant form of TgPF (rTgPF) incombination with T. gondii densegranule GRA7 recombinant protein (rGRA7). Mice were intradermaly immunized 4times with a 2-week interval with rTgPF, rGRA7, rGRA7+ACF or rGRA7+rTgPF. rTgPFsignificantly enhanced anti-GRA7 IgG levels compared to rGRA7 without adjuvant(p<0,05), reaching values similarto the ACF adjuvanted group. The humoral response either in rGRA7+ACF orrGRA7+rTgPF showed a mixed Th1/Th2 profile. rGRA7 in vitro stimulation of splenocytes induced significant and similarproliferative responses in mice vaccinated with rGRA7+rTgPF and rGRA7+ACF (p<0,05 vs control), while rGRA7+rTgPFgenerated higher levels of IFN-γ and IL-10secretion compared to the rGRA7+ACF (p<0,05).No specific humoral response against rTgPF could be detected in anyexperimental group. However, a significant proliferative response (p<0,05 vs control) with a Th1 profile(p<0,05 vs control) was generatedafter rTgPF in vitro stimulation ofsplenocytes from rTgPF and rGRA7+rTgPF immunized mice. Together these resultsshow that TgPF is an attractive adjuvant candidate for the development of a vaccineagainst toxoplasmosis