Inoculation of the leishmania infantum hsp70-ii null mutant induces long-term protection against l. Amazonensis infection in balb/c mice

Leishmania amazonensis parasites are etiological agents of cutaneous leishmaniasis in the New World. BALB/c mice are highly susceptible to L. amazonensis challenge due to their inability to mount parasite-dependent IFN--mediated responses. Here, we analyzed the capacity of a single administration of the LiDHSP70-II genetically-modified attenuated L. infantum line in preventing cutaneous leishmaniasis in mice challenged with L. amazonensis virulent parasites. In previous studies, this live attenuated vaccine has demonstrated to induce long-protection against murine leishmaniasis due to OldWorld Leishmania species. Vaccinated mice showed a reduction in the disease evolution due to L. amazonensis challenge, namely reduction in cutaneous lesions and parasite burdens. In contrast to control animals, after the challenge, protected mice showed anti-Leishmania IgG2a circulating antibodies accompanied to the induction of Leishmania-driven specific IFN- systemic response. An analysis performed in the lymph node draining the site of infection revealed an increase of the parasite-specific IFN-upgamma production by CD4+ and CD8+ T cells and a decrease in the secretion of IL-10 against leishmanial antigens. Since the immunity caused by the inoculation of this live vaccine generates protection against different forms of murine leishmaniasis, we postulate LiDHSP70-II as a candidate for the development of human vaccinesMinisterio de Ciencia e Innovación FISPI11/00095 and FISPI14/00366 (FEDER FUNDING) to M.S. and RYC-2016-19463 and RTI2018-343 to S.I. J.M.R. and M.S. are funded by the Fondo de Investigaciones Sanitarias (ISCIII-RETICRD16/0027/008-FEDER). E.H.G. is supported by a FPI grant from the Spanish Ministerio de Ciencia e Innovación. Institutional grants from the Fundación Ramón Areces and Banco de Santande