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A LigA Three-Domain Region Protects Hamsters from Lethal Infection by Leptospira interrogans

The leptospiral LigA protein consists of 13 bacterial immunoglobulin-like (Big) domains and is the only purified recombinant subunit vaccine that has been demonstrated to protect against lethal challenge by a clinical isolate of Leptospira interrogans in the hamster model of leptospirosis. We determ...

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Autores principales: Coutinho, Mariana L., Choy, Henry A., Kelley, Melissa M., Matsunaga, James, Babbitt, Jane T., Lewis, Michael S., Aleixo, Jose Antonio G., Haake, David A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236721/
https://www.ncbi.nlm.nih.gov/pubmed/22180800
http://dx.doi.org/10.1371/journal.pntd.0001422
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author Coutinho, Mariana L.
Choy, Henry A.
Kelley, Melissa M.
Matsunaga, James
Babbitt, Jane T.
Lewis, Michael S.
Aleixo, Jose Antonio G.
Haake, David A.
author_facet Coutinho, Mariana L.
Choy, Henry A.
Kelley, Melissa M.
Matsunaga, James
Babbitt, Jane T.
Lewis, Michael S.
Aleixo, Jose Antonio G.
Haake, David A.
author_sort Coutinho, Mariana L.
collection PubMed
description The leptospiral LigA protein consists of 13 bacterial immunoglobulin-like (Big) domains and is the only purified recombinant subunit vaccine that has been demonstrated to protect against lethal challenge by a clinical isolate of Leptospira interrogans in the hamster model of leptospirosis. We determined the minimum number and location of LigA domains required for immunoprotection. Immunization with domains 11 and 12 was found to be required but insufficient for protection. Inclusion of a third domain, either 10 or 13, was required for 100% survival after intraperitoneal challenge with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130. As in previous studies, survivors had renal colonization; here, we quantitated the leptospiral burden by qPCR to be 1.2×10(3) to 8×10(5) copies of leptospiral DNA per microgram of kidney DNA. Although renal histopathology in survivors revealed tubulointerstitial changes indicating an inflammatory response to the infection, blood chemistry analysis indicated that renal function was normal. These studies define the Big domains of LigA that account for its vaccine efficacy and highlight the need for additional strategies to achieve sterilizing immunity to protect the mammalian host from leptospiral infection and its consequences.
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spelling pubmed-32367212011-12-16 A LigA Three-Domain Region Protects Hamsters from Lethal Infection by Leptospira interrogans Coutinho, Mariana L. Choy, Henry A. Kelley, Melissa M. Matsunaga, James Babbitt, Jane T. Lewis, Michael S. Aleixo, Jose Antonio G. Haake, David A. PLoS Negl Trop Dis Research Article The leptospiral LigA protein consists of 13 bacterial immunoglobulin-like (Big) domains and is the only purified recombinant subunit vaccine that has been demonstrated to protect against lethal challenge by a clinical isolate of Leptospira interrogans in the hamster model of leptospirosis. We determined the minimum number and location of LigA domains required for immunoprotection. Immunization with domains 11 and 12 was found to be required but insufficient for protection. Inclusion of a third domain, either 10 or 13, was required for 100% survival after intraperitoneal challenge with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130. As in previous studies, survivors had renal colonization; here, we quantitated the leptospiral burden by qPCR to be 1.2×10(3) to 8×10(5) copies of leptospiral DNA per microgram of kidney DNA. Although renal histopathology in survivors revealed tubulointerstitial changes indicating an inflammatory response to the infection, blood chemistry analysis indicated that renal function was normal. These studies define the Big domains of LigA that account for its vaccine efficacy and highlight the need for additional strategies to achieve sterilizing immunity to protect the mammalian host from leptospiral infection and its consequences. Public Library of Science 2011-12-13 /pmc/articles/PMC3236721/ /pubmed/22180800 http://dx.doi.org/10.1371/journal.pntd.0001422 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Coutinho, Mariana L.
Choy, Henry A.
Kelley, Melissa M.
Matsunaga, James
Babbitt, Jane T.
Lewis, Michael S.
Aleixo, Jose Antonio G.
Haake, David A.
A LigA Three-Domain Region Protects Hamsters from Lethal Infection by Leptospira interrogans
title A LigA Three-Domain Region Protects Hamsters from Lethal Infection by Leptospira interrogans
title_full A LigA Three-Domain Region Protects Hamsters from Lethal Infection by Leptospira interrogans
title_fullStr A LigA Three-Domain Region Protects Hamsters from Lethal Infection by Leptospira interrogans
title_full_unstemmed A LigA Three-Domain Region Protects Hamsters from Lethal Infection by Leptospira interrogans
title_short A LigA Three-Domain Region Protects Hamsters from Lethal Infection by Leptospira interrogans
title_sort liga three-domain region protects hamsters from lethal infection by leptospira interrogans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236721/
https://www.ncbi.nlm.nih.gov/pubmed/22180800
http://dx.doi.org/10.1371/journal.pntd.0001422
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