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IMMUNIZATION OF EXPERIMENTAL DOGS WITH SALIVARY PROTEINS FROM LUTZOMYIA LONGIPALPIS, USING DNA AND RECOMBINANT CANARYPOX VIRUS INDUCES IMMUNE RESPONSES CONSISTENT WITH PROTECTION AGAINST LEISHMANIA INFANTUM
Mosca da areia
Leishmaniose visceral canina
Vetores de doenças
Proteínas salivares
Sand fly
Canine visceral leishmaniasis
Disease vectors
Salivary proteins
Salivary proteins
Autor
Abbehusen, Melissa Moura Costa
Cunha, Jurema
Suarez, Martha Sena
Teixeira, Clarissa
Almeida, Valter dos Anjos
Pereira, Laís da Silva
Bordoni, Marcelo
Santana, Leonardo Gil
Solcà, Manuela da Silva
Fraga, Deborah Bittencourt Mothé
Fischer, Laurent
Bozza, Patricia Torres
Valenzuela, Jesus G.
Kamhawi, Shaden
Andrade, Bruno de Bezerril
Brodskyn, Claudia Ida
Cunha, Jurema
Suarez, Martha Sena
Teixeira, Clarissa
Almeida, Valter dos Anjos
Pereira, Laís da Silva
Bordoni, Marcelo
Santana, Leonardo Gil
Solcà, Manuela da Silva
Fraga, Deborah Bittencourt Mothé
Fischer, Laurent
Bozza, Patricia Torres
Valenzuela, Jesus G.
Kamhawi, Shaden
Andrade, Bruno de Bezerril
Brodskyn, Claudia Ida
Afiliación
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Teresina, PI, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Boerhinger Ingelheim. Laboratoire de Lyon Portes des Alpes. Lyon, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Vector Molecular Biology Unit. Laboratory of Malaria and Vector Research. Bethesda, MD, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brazil / Universidade Salvador. Laureate Universities. Salvador, BA, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Instituto de Ciências da Saúde. Salvador, BA, Brasil / Nacional de Ciência e Tecnologia de Investigação em Imunologia. São Paulo, SP, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Teresina, PI, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.
Boerhinger Ingelheim. Laboratoire de Lyon Portes des Alpes. Lyon, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
National Institutes of Health. National Institute of Allergy and Infectious Diseases. Vector Molecular Biology Unit. Laboratory of Malaria and Vector Research. Bethesda, MD, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brazil / Universidade Salvador. Laureate Universities. Salvador, BA, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Instituto de Ciências da Saúde. Salvador, BA, Brasil / Nacional de Ciência e Tecnologia de Investigação em Imunologia. São Paulo, SP, Brasil.
Resumen en ingles
Metacyclic Leishmania promastigotes are transmitted by sand flies that inject parasites and saliva into the host’s skin. Previous studies have demonstrated that DNA plasmids encoding Lutzomyia longipalpis salivary proteins LJM17 and LJL143, when used to immunize dogs, resulted in a systemic and local Th1 cell-mediated immunity that interfered in parasite survival in vitro. Here we evaluated the ability of these same salivary antigens to induce anti-Leishmania immunity and to confer protection by
immunizing dogs using a novel vaccination strategy more suitable for use in the field. The strategy consisted of a single dose of plasmid followed by two doses of recombinant Canarypoxvirus (rCanarypoxvirus) expressing L. longipalpis salivary proteins (LJM17 or LJL143). Thirty days after the final immunization, dogs were intradermally challenged with 107 Leishmania infantum promastigotes in the presence of L. longipalpis saliva. We followed the experimentally infected dogs for 10 months to characterize clinical,
parasitological, and immunological parameters. Upon vaccination, all immunized dogs presented strong and specific humoral responses with increased serum concentrations of IFN-g, TNF, IL-7, and IL-15. The serum of dogs immunized with LJM17 also exhibited high levels of IL-2, IL-6, and IL-18. L. infantum infection was established in all experimental groups as evidenced by the presence of anti-Leishmania IgG, and by parasite detection in the spleen and skin. Dogs immunized with LJM17-based vacines presented higher circulating levels of IFN-g, IL-2, IL-6, IL-7, IL-15, IL-18, TNF, CXCL10, and GM-CSF post-infection when compared with controls. Results demonstrated that relevant Leishmania-specific immune responses were induced following vaccination of dogs with L. longipalpis salivary antigen LJM17 administered in a single priming dose of plasmid DNA, followed by two booster doses of recombinant Canarypox vector.
Importantly, a significant increase in pro-inflammatory cytokines and chemokines known to be relevant for protection against leishmaniasis was evidenced after challenging LJM17-vaccinated dogs as compared to controls. Although similar results were observed following immunization with LJL143, the pro-inflammatory response observed after immunization was attenuated following infection. Collectively, these data suggest that the
LJM17-based vaccine induced an immune profile consistent with the expected protective immunity against canine leishmaniosis. These results clearly support the need for further evaluation of the LJM17 antigen, using a heterologous prime-boost vaccination strategy against canine visceral leishmaniosis (CVL).
Palabras clave en portugues
VacinaMosca da areia
Leishmaniose visceral canina
Vetores de doenças
Proteínas salivares
Palabras clave en ingles
VaccineSand fly
Canine visceral leishmaniasis
Disease vectors
Salivary proteins
Salivary proteins
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