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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| Veröffentlicht in: | PLoS neglected tropical diseases 2011-12, Vol.5 (12), p.e1422-e1422 |
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| creator | Coutinho, Mariana L Choy, Henry A Kelley, Melissa M Matsunaga, James Babbitt, Jane T Lewis, Michael S Aleixo, Jose Antonio G Haake, David A |
| 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. |
| doi_str_mv | 10.1371/journal.pntd.0001422 |
| format | Article |
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The work is made available under the Creative Commons CC0 public domain dedication. 2011</rights><rights>2011 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Citation: Coutinho ML, Choy HA, Kelley MM, Matsunaga J, Babbitt JT, et al. (2011) A LigA Three-Domain Region Protects Hamsters from Lethal Infection by Leptospira interrogans. 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Choy, Henry A ; Kelley, Melissa M ; Matsunaga, James ; Babbitt, Jane T ; Lewis, Michael S ; Aleixo, Jose Antonio G ; Haake, David A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c622t-fab66b711f1330c45086e876364acc4e30f27c2f54defad7afd9a2e523824e1d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Antigens, Bacterial - chemistry</topic><topic>Antigens, Bacterial - genetics</topic><topic>Antigens, Bacterial - immunology</topic><topic>Bacterial infections</topic><topic>Bacterial Proteins - chemistry</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - immunology</topic><topic>Bacterial vaccines</topic><topic>Bacterial Vaccines - administration & dosage</topic><topic>Bacterial Vaccines - immunology</topic><topic>Biology</topic><topic>Body Weight</topic><topic>Cricetinae</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Experiments</topic><topic>Female</topic><topic>Health aspects</topic><topic>Immune response</topic><topic>Immunoglobulins</topic><topic>Kidney - microbiology</topic><topic>Kidney - pathology</topic><topic>Leptospira interrogans - chemistry</topic><topic>Leptospira interrogans - genetics</topic><topic>Leptospira interrogans - immunology</topic><topic>Leptospirosis</topic><topic>Leptospirosis - immunology</topic><topic>Leptospirosis - prevention & control</topic><topic>Mesocricetus</topic><topic>Mortality</topic><topic>Prevention</topic><topic>Protein Structure, Tertiary</topic><topic>Proteins</topic><topic>Recombinant Proteins</topic><topic>Risk factors</topic><topic>Survival Analysis</topic><topic>Tropical diseases</topic><topic>Vaccines</topic><topic>Vaccines, Attenuated - administration & dosage</topic><topic>Vaccines, Attenuated - immunology</topic><topic>Vaccines, Synthetic - administration & dosage</topic><topic>Vaccines, Synthetic - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Coutinho, Mariana L</creatorcontrib><creatorcontrib>Choy, Henry A</creatorcontrib><creatorcontrib>Kelley, Melissa M</creatorcontrib><creatorcontrib>Matsunaga, James</creatorcontrib><creatorcontrib>Babbitt, Jane T</creatorcontrib><creatorcontrib>Lewis, Michael S</creatorcontrib><creatorcontrib>Aleixo, Jose Antonio G</creatorcontrib><creatorcontrib>Haake, David A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Coutinho, Mariana L</au><au>Choy, Henry A</au><au>Kelley, Melissa M</au><au>Matsunaga, James</au><au>Babbitt, Jane T</au><au>Lewis, Michael S</au><au>Aleixo, Jose Antonio G</au><au>Haake, David A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A LigA three-domain region protects hamsters from lethal infection by Leptospira interrogans</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2011-12-01</date><risdate>2011</risdate><volume>5</volume><issue>12</issue><spage>e1422</spage><epage>e1422</epage><pages>e1422-e1422</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22180800</pmid><doi>10.1371/journal.pntd.0001422</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis of Variance Animals Antigens, Bacterial - chemistry Antigens, Bacterial - genetics Antigens, Bacterial - immunology Bacterial infections Bacterial Proteins - chemistry Bacterial Proteins - genetics Bacterial Proteins - immunology Bacterial vaccines Bacterial Vaccines - administration & dosage Bacterial Vaccines - immunology Biology Body Weight Cricetinae Deoxyribonucleic acid DNA Experiments Female Health aspects Immune response Immunoglobulins Kidney - microbiology Kidney - pathology Leptospira interrogans - chemistry Leptospira interrogans - genetics Leptospira interrogans - immunology Leptospirosis Leptospirosis - immunology Leptospirosis - prevention & control Mesocricetus Mortality Prevention Protein Structure, Tertiary Proteins Recombinant Proteins Risk factors Survival Analysis Tropical diseases Vaccines Vaccines, Attenuated - administration & dosage Vaccines, Attenuated - immunology Vaccines, Synthetic - administration & dosage Vaccines, Synthetic - immunology |
| title | A LigA three-domain region protects hamsters from lethal infection by Leptospira interrogans |
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