title: A sand fly salivary protein vaccine shows efficacy against vector-transmitted cutaneous leishmaniasis in nonhuman primates.
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.
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: Fabiano
authors.initials: F
authors.lastname: Oliveira
authors.affiliation: Department of Entomology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Edgar
authors.initials: E
authors.lastname: Rowton
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: Hamide
authors.initials: H
authors.lastname: Aslan
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. Centro de Pesquisas Gonçalo Moniz (CPqGM)-Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia 40296-710, Brazil.
authors.forename: Regis
authors.initials: R
authors.lastname: Gomes
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Castrovinci
authors.affiliation: Laboratório de Bioquímica de Resposta ao Estresse, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Alvarenga
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: Maha
authors.initials: M
authors.lastname: Abdeladhim
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. Centro de Pesquisas Gonçalo Moniz (CPqGM)-Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Bahia 40296-710, Brazil.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Teixeira
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Meneses
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: Lindsey T
authors.initials: LT
authors.lastname: Kleeman
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: Anderson B
authors.initials: AB
authors.lastname: Guimarães-Costa
authors.affiliation: Department of Entomology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Tobin E
authors.initials: TE
authors.lastname: Rowland
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Gilmore
authors.affiliation: Faculty of Medicine, Pharmacy and Odontostomatology, University of Bamako, Bamako 1805, Mali.
authors.forename: Seydou
authors.initials: S
authors.lastname: Doumbia
authors.affiliation: Infectious Disease Research Institute, Seattle, WA 98102, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.affiliation: Department of Entomology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Lawyer
authors.affiliation: Vector Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Andersen
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. jvalenzuela@niaid.nih.gov skamhawi@niaid.nih.gov.
authors.forename: Shaden
authors.initials: S
authors.lastname: Kamhawi
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. jvalenzuela@niaid.nih.gov skamhawi@niaid.nih.gov.
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Valenzuela
mesh_terms: D000818:Animals; D006801:Humans; D007303:Insect Vectors; D016773:Leishmaniasis, Cutaneous / Q000628:therapy*; D011323:Primates; D016052:Protozoan Vaccines / Q000627:therapeutic use*; D011576:Psychodidae / Q000469:parasitology*; D012471:Salivary Proteins and Peptides / Q000276:immunology*
chemical_list: D016052:Protozoan Vaccines; D012471:Salivary Proteins and Peptides