A sand fly salivary protein vaccine shows efficacy against vector-transmitted cutaneous leishmaniasis in nonhuman primates

Fabiano Oliveira, Edgar Rowton, Hamide Aslan, Regis Gomes, Philip A. Castrovinci, Patricia H. Alvarenga, Maha Abdeladhim, Clarissa Teixeira, Claudio Meneses, Lindsey T. Kleeman, Anderson B. Guimarães-Costa, Tobin E. Rowland, Dana Gilmore, Seydou Doumbia, Steven G. Reed, Phillip G. Lawyer, John F. Andersen, Shaden Kamhawi, Jesus G. Valenzuela

Research output: Contribution to journalArticlepeer-review

Abstract

Currently, there are no commercially available human vaccines against leishmaniasis. In rodents, cellular immunity to salivary proteins of sand fly vectors is associated to protection against leishmaniasis, making them worthy targets for further exploration as vaccines. We demonstrate that nonhuman primates (NHP) exposed to Phlebotomus duboscqi uninfected sand fly bites or immunized with salivary protein PdSP15 are protected against cutaneous leishmaniasis initiated by infected bites. Uninfected sand fly-exposed and 7 of 10 PdSP15-immunized rhesus macaques displayed a significant reduction in disease and parasite burden compared to controls. Protection correlated to the early appearance of Leishmania-specific CD4+IFN-γ+ lymphocytes, suggesting that immunity to saliva or PdSP15 augments the host immune response to the parasites while maintaining minimal pathology. Notably, the 30% unprotected PdSP15-immunized NHP developed neither immunity to PdSP15 nor an accelerated Leishmania-specific immunity. Sera and peripheral blood mononuclear cells from individuals naturally exposed to P. duboscqi bites recognized PdSP15, demonstrating its immunogenicity in humans. PdSP15 sequence and structure show no homology to mammalian proteins, further demonstrating its potential as a component of a vaccine for human leishmaniasis.

Original languageEnglish (US)
Article number290ra90
JournalScience translational medicine
Volume7
Issue number290
DOIs
StatePublished - Jun 3 2015

ASJC Scopus subject areas

  • Medicine(all)

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