DUAL ROLE OF THE TLR-AGONIST PROFILIN PROTEIN FROM TOXOPLASMA GONDII: STUDY OF THE ADJUVANT AND IMMUNOGENIC VALUE IN A VACCINE FORMULATION IN TWO MOUSE STRAINS WITH DIFFERENT SUSCEPTIBILITY

ARCÓN, N; M PICCHIO; V SANCHEZ; R MORETTA; I FENOY; A SOTO; M PERRONE SIBILIA; ALDIRICO MA; A GOLDMAN; V MARTÍN

Mar del Plata

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Inmunología 2018; 2018

SAI

Toxoplasmosis is a disease that affects 30% ofthe world?s popu­lation. At present, there are no pharmacological treatmentsthat eliminate the parasite or vaccines that confer protection to the host. Theaim of the present work was to study the immunogenicity of a vaccineformulation containing a recombinant form of the T. gon­dii Profilinprotein (rTgPF), a TLR ligand, in combination with the dense granule GRA7protein (rGRA7), in two mouse strains with dif­ferent susceptibility to chronictoxoplasmosis. BALB/c and C57BL/6 mice were intradermally immunized 3-timeswith a 2-week interval with: rGRA7, rTgPF, rGRA7+rTgPF, rGRA7+ACF. Naive micewere used as control. While in BALB/c mice rGRA7+rTgPF vaccination generated ananti-GRA7 humoral response with a Th1 profile and rGRA7+ACF showed a mixedprofile, both formulations induced a mixed profile in C57BL/6 mice. Ex vivo stimulationof splenocytes with rGRA7 induced significant proliferative responses(p<0.05) and IFN-γproduction (p<0.05) in rGRA7+rTgPF and rGRA7+ACF groups of both mousestrains. In addition, although rTgPF generated very low humoral responses inboth mouse strains, significant pro­liferative responses (p<0.05) and IFN-γ production (p<0.05) weredetected in rTgPF-stimulated splenocytes from both rGRA7+rTgPF and rTgPFgroups. After an oral challenge with a non-lethal dose of T. gondii cysts,a 62% reduction in brain parasite load compared to control was obtained withrGRA7+rTgPF vaccine formulation in BALB/c (p<0.05), similarly to the levelobtained with rGRA7+ACF. In contrast, none of the vaccines induced protectionin C57BL/6 mice. These results demonstrate a dual role of rTgPF. As an adjuvantwith capacity to enhance the immunogenicity of another antigen, and also as animmunogen given its ability to induce specific-cellular re­sponses. We alsoshowed the importance of the genetic background of experimental animals whenevaluating vaccination protocols, therefore highlighting the importance oftesting the same vaccine formulation in animals with different haplotypes