Alpha-galactosylceramide as adjuvant induces protective cell-mediated immunity against Leishmania mexicana infection in vaccinated BALB/c mice.

Adjuvants represent a promising strategy to improve vaccine effectiveness against infectious diseases such as leishmaniasis. Vaccination with the invariant natural killer T cell ligand α-galactosylceramide (αGalCer) has been used successfully as adjuvant, generating a Th1-biased immunomodulation. This glycolipid enhances experimental vaccination platforms against intracellular parasites including Plasmodium yoelii and Mycobacterium tuberculosis. In the present study, we assessed the protective immunity induced by a single-dose intraperitoneal injection of αGalCer (2 µg) co-administrated with a lysate antigen of amastigotes (100 µg) against Leishmania mexicana infection in BALB/c mice. The prophylactic vaccination led to 5.0-fold reduction of parasite load at the infection site, compared to non-vaccinated mice. A predominant pro-inflammatory response was observed in challenged vaccinated mice, represented by a 1.9 and 2.8-fold-increase of IL-1ß and IFN-γ producing cells, respectively, in the lesions, and by 23.7-fold-increase of IFN-γ production in supernatants of restimulated splenocytes, all compared to control groups. The co-administration of αGalCer also stimulated the maturation of splenic dendritic cells and modulated a Th1-skewed immune response, with high amounts of IFN-γ production in serum. Furthermore, peritoneal cells of αGalCer-immunized mice exhibited an elevated expression of Ly6G and MHCII. These findings indicate that αGalCer improves protection against cutaneous leishmaniasis, supporting evidence for its potential use as adjuvant in Leishmania-vaccines.