The TLR agonist profilin protein from Toxoplasma gondii generates protection in an experimental vaccine

NADIA ARCON, MARIANO SERGIO PICCHIO, VANESA ROXANA SANCHEZ, IGNACIO MARTIN FENOY, ROSALIA ESTHER MORETTA, MATIAS DAMIAN PERRONE SIBILIA, ARIADNA SOLEDAD SOTO, MARIA DE LOS ANGELES ALDIRICO, ALEJANDRA GOLDMAN, VALENTINA MARTIN

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Toxoplasmosis is a disease that affects 30% of the world's population.At present, there are no pharmacological treatments that eliminate the parasiteor vaccines that confer protection to the host. In this work we studied the adjuvantand/or immunogenic value of a recombinant form of T. gondii Profilin protein (rTgPF), a TLR ligand, in a vaccinestrategy using a murine model of chronic toxoplasmosis. BALB/c mice, with highresistance to this infection, were intradermal immunized 3 times with a 2-weekinterval with: rGRA7 (recombinant T.gondii dense granule 7 protein), rTgPF, rGRA7+rTgPF or rGRA7+ACF.The anti-GRA7humoral response showed a Th1 profile when rTgPF was used as adjuvant(IgG1/IgG2a ratio: 0,6±0,5), while rGRA7+ACF showed a mixed profile (IgG1/IgG2a ratio: 1,3±0,5). Splenocytes from rGRA7+rTgPF and rGRA7+ACF mice stimulatedwith rGRA7, showed similar levels of proliferative responses that weresignificantly higher than the control group (p <0.05), and alsosignificant production of IFN-γ (p <0.05 vs control). In addition, although rTgPF generated a low humoralresponse, this presented a Th1 profile both in rTgPF and rGRA7+rTgPF groups(IgG1/IgG2a ratio: 0,4±0,1 and0,4±0,1 respectively). After rTgPF in vitro stimulation of splenocytes, significantproliferative responses and also significant production of IFN-γ were detected in rGRA7+rTgPF mice compared to the control group (p<0.01). When vaccinated mice were orally challenged with a non-lethal dose of T. gondii cysts, rGRA7+rTgPF mice presented a 62% reduction in the cysts number per brain compared tothe control group (p<0,05). This reduction resulted similar to the observedfor the rGRA7+ACF group. Together these results demonstrate the dual role of rTgPF: as an adjuvant with capacity to enhance immuneresponses against another antigen, and also as an immunogen given its ability toinduce specific responses. We conclude that Profilin is a valuable candidate toinclude in a vaccine against toxoplasmosis