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Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice

BACKGROUND: We have previously demonstrated that intranasal vaccination of highly susceptible BALB/c mice with whole Leishmania amazonensis antigens (LaAg) leads to protection against murine cutaneous leishmaniasis. Here, we evaluate the response of partially resistant C57BL/6 mice to vaccination as...

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Autores principales: Pratti, Juliana Elena Silveira, Ramos, Tadeu Diniz, Pereira, Joyce Carvalho, da Fonseca-Martins, Alessandra Marcia, Maciel-Oliveira, Diogo, Oliveira-Silva, Gabriel, de Mello, Mirian França, Chaves, Suzana Passos, Gomes, Daniel Claudio Oliveira, Diaz, Bruno Lourenço, Rossi-Bergmann, Bartira, de Matos Guedes, Herbert Leonel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052793/
https://www.ncbi.nlm.nih.gov/pubmed/27716449
http://dx.doi.org/10.1186/s13071-016-1822-9
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author Pratti, Juliana Elena Silveira
Ramos, Tadeu Diniz
Pereira, Joyce Carvalho
da Fonseca-Martins, Alessandra Marcia
Maciel-Oliveira, Diogo
Oliveira-Silva, Gabriel
de Mello, Mirian França
Chaves, Suzana Passos
Gomes, Daniel Claudio Oliveira
Diaz, Bruno Lourenço
Rossi-Bergmann, Bartira
de Matos Guedes, Herbert Leonel
author_facet Pratti, Juliana Elena Silveira
Ramos, Tadeu Diniz
Pereira, Joyce Carvalho
da Fonseca-Martins, Alessandra Marcia
Maciel-Oliveira, Diogo
Oliveira-Silva, Gabriel
de Mello, Mirian França
Chaves, Suzana Passos
Gomes, Daniel Claudio Oliveira
Diaz, Bruno Lourenço
Rossi-Bergmann, Bartira
de Matos Guedes, Herbert Leonel
author_sort Pratti, Juliana Elena Silveira
collection PubMed
description BACKGROUND: We have previously demonstrated that intranasal vaccination of highly susceptible BALB/c mice with whole Leishmania amazonensis antigens (LaAg) leads to protection against murine cutaneous leishmaniasis. Here, we evaluate the response of partially resistant C57BL/6 mice to vaccination as a more representative experimental model of human cutaneous leishmaniasis. METHODS: C57BL/6 mice from different animal facilities were infected with L. amazonensis (Josefa strain) to establish the profile of infection. Intranasal vaccination was performed before the infection challenge with two doses of 10 μg of LaAg alone or associated with the adjuvant ADDAVAX® by instillation in the nostrils. The lesion progression was measured with a dial caliper and the parasite load by limited dilution assay in the acute and chronic phases of infection. Cytokines were quantified by ELISA in the homogenates of infected footpads. RESULTS: C57BL/6 mice from different animal facilities presented the same L. amazonensis infection profile, displaying a progressive acute phase followed by a controlled chronic phase. Parasites cultured in M199 and Schneider’s media were equally infective. Intranasal vaccination with LaAg led to milder acute and chronic phases of the disease. The mechanism of protection was associated with increased production of IFN-gamma in the infected tissue as measured in the acute phase. Association with the ADDAVAX® adjuvant did not improve the efficacy of intranasal LaAg vaccination. Rather, ADDAVAX® reduced vaccination efficacy. CONCLUSION: This study demonstrates that the efficacy of adjuvant-free intranasal vaccination with LaAg is extendable to the more resistant C57Bl/6 mouse model of infection with L. amazonensis, and is thus not exclusive to the susceptible BALB/c model. These results imply that mucosal immunomodulation by LaAg leads to peripheral protection irrespective of the genetic background of the host. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1822-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-50527932016-10-06 Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice Pratti, Juliana Elena Silveira Ramos, Tadeu Diniz Pereira, Joyce Carvalho da Fonseca-Martins, Alessandra Marcia Maciel-Oliveira, Diogo Oliveira-Silva, Gabriel de Mello, Mirian França Chaves, Suzana Passos Gomes, Daniel Claudio Oliveira Diaz, Bruno Lourenço Rossi-Bergmann, Bartira de Matos Guedes, Herbert Leonel Parasit Vectors Research BACKGROUND: We have previously demonstrated that intranasal vaccination of highly susceptible BALB/c mice with whole Leishmania amazonensis antigens (LaAg) leads to protection against murine cutaneous leishmaniasis. Here, we evaluate the response of partially resistant C57BL/6 mice to vaccination as a more representative experimental model of human cutaneous leishmaniasis. METHODS: C57BL/6 mice from different animal facilities were infected with L. amazonensis (Josefa strain) to establish the profile of infection. Intranasal vaccination was performed before the infection challenge with two doses of 10 μg of LaAg alone or associated with the adjuvant ADDAVAX® by instillation in the nostrils. The lesion progression was measured with a dial caliper and the parasite load by limited dilution assay in the acute and chronic phases of infection. Cytokines were quantified by ELISA in the homogenates of infected footpads. RESULTS: C57BL/6 mice from different animal facilities presented the same L. amazonensis infection profile, displaying a progressive acute phase followed by a controlled chronic phase. Parasites cultured in M199 and Schneider’s media were equally infective. Intranasal vaccination with LaAg led to milder acute and chronic phases of the disease. The mechanism of protection was associated with increased production of IFN-gamma in the infected tissue as measured in the acute phase. Association with the ADDAVAX® adjuvant did not improve the efficacy of intranasal LaAg vaccination. Rather, ADDAVAX® reduced vaccination efficacy. CONCLUSION: This study demonstrates that the efficacy of adjuvant-free intranasal vaccination with LaAg is extendable to the more resistant C57Bl/6 mouse model of infection with L. amazonensis, and is thus not exclusive to the susceptible BALB/c model. These results imply that mucosal immunomodulation by LaAg leads to peripheral protection irrespective of the genetic background of the host. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-016-1822-9) contains supplementary material, which is available to authorized users. BioMed Central 2016-10-06 /pmc/articles/PMC5052793/ /pubmed/27716449 http://dx.doi.org/10.1186/s13071-016-1822-9 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Pratti, Juliana Elena Silveira
Ramos, Tadeu Diniz
Pereira, Joyce Carvalho
da Fonseca-Martins, Alessandra Marcia
Maciel-Oliveira, Diogo
Oliveira-Silva, Gabriel
de Mello, Mirian França
Chaves, Suzana Passos
Gomes, Daniel Claudio Oliveira
Diaz, Bruno Lourenço
Rossi-Bergmann, Bartira
de Matos Guedes, Herbert Leonel
Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice
title Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice
title_full Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice
title_fullStr Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice
title_full_unstemmed Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice
title_short Efficacy of intranasal LaAg vaccine against Leishmania amazonensis infection in partially resistant C57Bl/6 mice
title_sort efficacy of intranasal laag vaccine against leishmania amazonensis infection in partially resistant c57bl/6 mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052793/
https://www.ncbi.nlm.nih.gov/pubmed/27716449
http://dx.doi.org/10.1186/s13071-016-1822-9
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