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A SAND FLY SALIVARY PROTEIN VACCINE SHOWS EFFICACY AGAINST VECTOR-TRANSMITTED CUTANEOUS LEISHMANIASIS IN NON HUMAN PRIMATES.
Vacinas
Imunidade celular
Proteinas salivares
Saliva
Flebótomos
Animal
Leishmaniose Cutânea
Leishmaniose humana
Macacos rhesus
Author
Oliveira, Fabiano
Rowton, Edgar
Aslan, Hamide
Gomes, Regis Bernardo Brandim
Castrovinci, Philip A
Alvarenga, Patricia Hessab
Abdeladhim, Maha
Teixeira, Clarissa
Meneses, Claudio
Kleeman, Lindsey T
Costa, Anderson Guimarães Baptista
Rowland, Tobin E
Gilmore, Dana C
Doumbia, Seydou
Reed, Steven G
Lawyer, Philip G
Andersen, John F
Kamhawi, Shaden
Valenzuela, Jesus G
Rowton, Edgar
Aslan, Hamide
Gomes, Regis Bernardo Brandim
Castrovinci, Philip A
Alvarenga, Patricia Hessab
Abdeladhim, Maha
Teixeira, Clarissa
Meneses, Claudio
Kleeman, Lindsey T
Costa, Anderson Guimarães Baptista
Rowland, Tobin E
Gilmore, Dana C
Doumbia, Seydou
Reed, Steven G
Lawyer, Philip G
Andersen, John F
Kamhawi, Shaden
Valenzuela, Jesus G
Affilliation
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
Walter Read Army Institute of Research. Department of Entomology. Silver Spring, MD, USA
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
Universidade Federal do Rio de Janeiro. Instituto de Bioquimica Medica. Laboratório de Bioquímica e Resposta ao Estresse. Rio de Janeiro, RJ, Brasil
Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular. Rio de Janeiro, RJ, Brasil
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
Walter Read Army Institute of Research. Department of Entomology. Silver Spring, MD, USA
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
University of Bamaco. Faculty of Medicine, Pharmacy and Odontostomatology. Bamako, Mali
Infection Disease Research Institute. Seattle, WA, USA
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Diyarbakir, Turkey
Walter Read Army Institute of Research. Department of Entomology. Silver Spring, MD, USA
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Diyarbakir, Turkey
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
Walter Read Army Institute of Research. Department of Entomology. Silver Spring, MD, USA
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
Universidade Federal do Rio de Janeiro. Instituto de Bioquimica Medica. Laboratório de Bioquímica e Resposta ao Estresse. Rio de Janeiro, RJ, Brasil
Universidade Federal do Rio de Janeiro. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular. Rio de Janeiro, RJ, Brasil
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
Walter Read Army Institute of Research. Department of Entomology. Silver Spring, MD, USA
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
University of Bamaco. Faculty of Medicine, Pharmacy and Odontostomatology. Bamako, Mali
Infection Disease Research Institute. Seattle, WA, USA
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Diyarbakir, Turkey
Walter Read Army Institute of Research. Department of Entomology. Silver Spring, MD, USA
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Diyarbakir, Turkey
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
National Institutes of Allergy and Infectious Disease. Laboratory of Malaria and Vector. Vector Molecular Biology Section. Rockville, MD, USA
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.
Keywords in Portuguese
LeishmanioseVacinas
Imunidade celular
Proteinas salivares
Saliva
Flebótomos
Animal
Leishmaniose Cutânea
Leishmaniose humana
Macacos rhesus
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