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IMMUNITY TO A SALIVARY PROTEIN OF A SAND FLY VECTOR PROTECTS AGAINST THE FATAL OUTCOME OF VISCERAL LEISHMANIASIS IN A HAMSTER MODEL
Gomes, Regis Bernardo Brandim et al. | Date Issued: 2008
Author
Gomes, Regis Bernardo Brandim
Teixeira, Clarissa Romero
Teixeira, Maria Jânia
Oliveira, Fabiano
Menezes, Maria José
Silva, Claire
Oliveira, Camila Indiani de
Miranda, José Carlos
Elnaiem, Dia-Eldin A
Kamhawi, Shaden
Valenzuela, Jesus G
Brodskyn, Claudia Ida
Affilliation
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Vector Molecular Biology Unit. National Institutes of Health. Twinbrook Parkway, Rockville, MD, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Vector Molecular Biology Unit. National Institutes of Health. Twinbrook Parkway, Rockville, MD, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Vector Molecular Biology Unit. National Institutes of Health. Twinbrook Parkway, Rockville, MD, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Vector Molecular Biology Unit. National Institutes of Health. Twinbrook Parkway, Rockville, MD, USA
National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Vector Molecular Biology Unit. National Institutes of Health. Twinbrook Parkway, Rockville, MD, USA
National Institute of Allergy and Infectious Diseases. Laboratory of Malaria and Vector Research. Vector Molecular Biology Unit. National Institutes of Health. Twinbrook Parkway, Rockville, MD, USA /
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Instituto de Investigação em Imunologia. Salvador, BA, Brasil
Abstract
Visceral leishmaniasis (VL) is a fatal disease for humans, and no vaccine is currently available. Sand fly salivary proteins have been associated with protection against cutaneous leishmaniasis. To test whether vector salivary proteins can protect against VL, a hamster model was developed involving intradermal inoculation in the ears of 100,000 Leishmania infantum chagasi parasites together with Lutzomyia longipalpis saliva to mimic natural transmission by sand flies. Hamsters developed classical signs of VL rapidly, culminating in a fatal outcome 5–6 months postinfection. Saliva had no effect on the course of infection in this model. Immunization with 16 DNA plasmids coding for salivary proteins of Lu. longipalpis resulted in the identification of LJM19, a novel 11-kDa protein, that protected hamsters against the fatal outcome of VL. LJM19-immunized hamsters maintained a low parasite load that correlated with an overall high IFN- /TGF- ratio and inducible NOS expression in the spleen and liver up to 5 months postinfection. Importantly, a delayed-type hypersensitivity response with high expression of IFN- was also noted in the skin of LJM19-immunized hamsters 48 h after exposure to uninfected sand fly bites. Induction of IFN- at the site of bite could partly explain the protection observed in the viscera of LJM19-immunized hamsters through direct parasite killing and/or priming of anti-Leishmania immunity. We have shown that immunity to a defined salivary protein (LJM19) confers powerful protection against the fatal outcome of a parasitic disease, which reinforces the concept of using components of arthropod saliva in vaccine strategies against vector-borne diseases.
Keywords in Portuguese
Imunidade Antisaliva
Leishmania
Vetor de Vacinas
 
Keywords
Antisaliva Immunity
Leishmania
Sand fly saliva
Vector-based Vaccine
 
DeCS
Animais
Cricetinae
Modelos Animais de Doenças
Humanos
Imunidade
Mordeduras e Picadas de Insetos
Proteínas de Insetos
Insetos Vetores
Interferon gama
Vacinas contra Leishmaniose
Leishmaniose Visceral
Plasmídeos
Psychodidae
Proteínas e Peptídeos Salivares
Vacinação
 
Publisher
National Academy of Sciences
Citation
GOMES, R. et al. Immunity to a salivary protein of a sand fly vector protects against the fatal outcome of visceral leishmaniasis in a hamster model. Proceedings of the National Academy of Sciences of the United States of America, v.105, n.22, p.7845-7850, jun. 2008.
ISSN
0027-8424
Notes
Agradecimentos a Dra. Aldina Barral, Dr. Manoel Barral Netto, Dr. MC José Ribeiro, e Ryan Jochim pela revisão crítica deste manuscrito; Ao Dr. Robert Gwadz pelo apoio contínuo; a Sheila Dreher pela construção de DNA dos plasmídeos; Edivaldo Passos pela assistência técnica, e Nancy Shulman pela assistência editorial.