The F1F3 recombinant chimera induced higher vaccine efficacy than its independent F1 and F3 components against Leishmania (L.) infantum chagasi mice infection.

Daniele Crespo GomesMaria Paula Fonseca-RibeiroMARCUS VINICIUS SILVAClarisa B. Palatnik-de-Sousa^*

• Microbiologia Geral, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil

Visceral leishmaniasis (VL) is a severe human vector-borne CD4-immunosuppressive disease that can be lethal if untreated soon after symptoms arise. No vaccine is available against human VL, and its chemotherapy is highly toxic. Leishmania (L.) donovani nucleoside hydrolase (NH36) has been considered a vaccine candidate, among other Leishmania antigens. In mice vaccinated with NH36, protection against VL is mediated by a CD4+ T cell response to the NH36 C-terminal domain (F3), and against cutaneous leishmaniasis (CL), by a CD4+ response against F3 and a CD8+ response against the NH36 N-terminal (F1). Vaccination with a recombinant chimera containing the F1 and F3 domains expressed in tandem (F1F3) protected mice against the heterologous CL infection by L. (L.) amazonensis and L. (V.) braziliensis. In this investigation, BALB/c mice were immunized with either F1, F3, a mixture of both, or with the F1F3 chimera, plus saponin, and challenged with amastigotes of L. (L.) infantum chagasi, the agent of VL in America. The F1F3 chimera and the F3 vaccines promoted the highest IgA, IgM, IgG, IgG1, IgG2a, IgG2b, and IgG3 antibody responses. The F1F3 chimera promoted the strongest intradermal response against the leishmanial antigen, the highest body weight gain, and the most potent spleen and liver relative weights reduction. In addition, the F1F3 chimera vaccine increased the secretion of IFN-γ, and, together with the F3 vaccine, the secretion of TNF-α by splenocytes. The F1F3 chimera and the F1 vaccine also promoted the strongest secretion of IL-10, which was very low in mice immunized with F3. Thus, the IFN-γ/IL-10 and TNF-α/IL-10 ratios, characteristic of a Th1 response, were increased in mice vaccinated with F3. The F1F3 chimera and the F3 vaccine reduced the parasite load in the liver. Therefore, the F1F3 chimera, as described for the heterologous CL infections, also optimizes protection against the homologous visceral leishmaniasis infection by L. (L.) infantum chagasi, by a Th1 contribution from the F3 peptide and a regulatory response from the F1 peptide. Expression of the F1 and F3 domains in tandem induced higher efficacy than the simple mixture of the F1 and F3 domains.