Evaluating the A-Subunit of the Heat-Labile Toxin (LT) As an Immunogen and a Protective Antigen Against Enterotoxigenic Escherichia coli (ETEC)
Diarrheal illness contributes to malnutrition, stunted growth, impaired cognitive development, and high morbidity rates in children worldwide. Enterotoxigenic Escherichia coli (ETEC) is a major contributor to this diarrheal disease burden. ETEC cause disease in the small intestine by means of coloni...
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| description | Diarrheal illness contributes to malnutrition, stunted growth, impaired cognitive development, and high morbidity rates in children worldwide. Enterotoxigenic Escherichia coli (ETEC) is a major contributor to this diarrheal disease burden. ETEC cause disease in the small intestine by means of colonization factors and by production of a heat-labile enterotoxin (LT) and/or a small non-immunogenic heat-stable enterotoxin (ST). Overall, the majority of ETEC produce both ST and LT. LT induces secretion via an enzymatically active A-subunit (LT-A) and a pentameric, cell-binding B-subunit (LT-B). The importance of anti-LT antibodies has been demonstrated in multiple clinical and epidemiological studies, and a number of potential ETEC vaccine candidates have included LT-B as an important immunogen. However, there is limited information about the potential contribution of LT-A to development of protective immunity. In the current study, we evaluate the immune response against the A-subunit of LT as well as the A-subunit's potential as a protective antigen when administered alone or in combination with the B-subunit of LT. We evaluated human sera from individuals challenged with a prototypic wild-type ETEC strain as well as sera from individuals living in an ETEC endemic area for the presence of anti-LT, anti-LT-A and anti-LT-B antibodies. In both cases, a significant number of individuals intentionally or endemically infected with ETEC developed antibodies against both LT subunits. In addition, animals immunized with the recombinant proteins developed robust antibody responses that were able to neutralize the enterotoxic and cytotoxic effects of native LT by blocking binding and entry into cells (anti-LT-B) or the intracellular enzymatic activity of the toxin (anti-LT-A). Moreover, antibodies to both LT subunits acted synergistically to neutralize the holotoxin when combined. Taken together, these data support the inclusion of both LT-A and LT-B in prospective vaccines against ETEC. |
| doi_str_mv | 10.1371/journal.pone.0136302 |
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Enterotoxigenic Escherichia coli (ETEC) is a major contributor to this diarrheal disease burden. ETEC cause disease in the small intestine by means of colonization factors and by production of a heat-labile enterotoxin (LT) and/or a small non-immunogenic heat-stable enterotoxin (ST). Overall, the majority of ETEC produce both ST and LT. LT induces secretion via an enzymatically active A-subunit (LT-A) and a pentameric, cell-binding B-subunit (LT-B). The importance of anti-LT antibodies has been demonstrated in multiple clinical and epidemiological studies, and a number of potential ETEC vaccine candidates have included LT-B as an important immunogen. However, there is limited information about the potential contribution of LT-A to development of protective immunity. In the current study, we evaluate the immune response against the A-subunit of LT as well as the A-subunit's potential as a protective antigen when administered alone or in combination with the B-subunit of LT. We evaluated human sera from individuals challenged with a prototypic wild-type ETEC strain as well as sera from individuals living in an ETEC endemic area for the presence of anti-LT, anti-LT-A and anti-LT-B antibodies. In both cases, a significant number of individuals intentionally or endemically infected with ETEC developed antibodies against both LT subunits. In addition, animals immunized with the recombinant proteins developed robust antibody responses that were able to neutralize the enterotoxic and cytotoxic effects of native LT by blocking binding and entry into cells (anti-LT-B) or the intracellular enzymatic activity of the toxin (anti-LT-A). Moreover, antibodies to both LT subunits acted synergistically to neutralize the holotoxin when combined. Taken together, these data support the inclusion of both LT-A and LT-B in prospective vaccines against ETEC.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0136302</identifier><identifier>PMID: 26305793</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antibodies ; Antibodies, Bacterial - blood ; Antibodies, Bacterial - immunology ; Antibodies, Neutralizing - blood ; Antibodies, Neutralizing - immunology ; Antigens ; Antigens, Bacterial - genetics ; Antigens, Bacterial - immunology ; Bacteria ; Bacterial Toxins - chemistry ; Bacterial Toxins - genetics ; Bacterial Toxins - immunology ; Binding ; Cell Line ; Children ; Cholera ; Cognitive ability ; Colonization ; Cytotoxicity ; Diarrhea ; Disease Models, Animal ; E coli ; Enterotoxigenic Escherichia coli - genetics ; Enterotoxigenic Escherichia coli - immunology ; Enterotoxins - chemistry ; Enterotoxins - genetics ; Enterotoxins - immunology ; Enzymatic activity ; Epidemiology ; Escherichia coli ; Escherichia coli Infections - epidemiology ; Escherichia coli Infections - immunology ; Escherichia coli Infections - prevention & control ; Escherichia coli Proteins - chemistry ; Escherichia coli Proteins - genetics ; Escherichia coli Proteins - immunology ; Heat ; Heat-labile enterotoxin ; Humans ; Immune response ; Immune system ; Immunity ; Immunity, Mucosal ; Immunization ; Immunogenicity ; Immunoglobulins ; Immunology ; Infections ; Lymphocytes B ; Malnutrition ; Mice ; Morbidity ; Mucous Membrane - immunology ; Mucous Membrane - microbiology ; Neutralization Tests ; Patients ; Protective antigen ; Protein Subunits - genetics ; Protein Subunits - immunology ; Proteins ; Small intestine ; Studies ; Thermal stability ; Tropical diseases ; Vaccines ; Vibrio cholerae</subject><ispartof>PloS one, 2015-08, Vol.10 (8), p.e0136302-e0136302</ispartof><rights>2015 Norton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Norton et al 2015 Norton et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-51599aa89ebfd1571228a6f1a8355f22c5722da0c4e23e755f7625484cee90103</citedby><cites>FETCH-LOGICAL-c526t-51599aa89ebfd1571228a6f1a8355f22c5722da0c4e23e755f7625484cee90103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549283/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549283/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26305793$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mantis, Nicholas J</contributor><creatorcontrib>Norton, Elizabeth B</creatorcontrib><creatorcontrib>Branco, Luis M</creatorcontrib><creatorcontrib>Clements, John D</creatorcontrib><title>Evaluating the A-Subunit of the Heat-Labile Toxin (LT) As an Immunogen and a Protective Antigen Against Enterotoxigenic Escherichia coli (ETEC)</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Diarrheal illness contributes to malnutrition, stunted growth, impaired cognitive development, and high morbidity rates in children worldwide. Enterotoxigenic Escherichia coli (ETEC) is a major contributor to this diarrheal disease burden. ETEC cause disease in the small intestine by means of colonization factors and by production of a heat-labile enterotoxin (LT) and/or a small non-immunogenic heat-stable enterotoxin (ST). Overall, the majority of ETEC produce both ST and LT. LT induces secretion via an enzymatically active A-subunit (LT-A) and a pentameric, cell-binding B-subunit (LT-B). The importance of anti-LT antibodies has been demonstrated in multiple clinical and epidemiological studies, and a number of potential ETEC vaccine candidates have included LT-B as an important immunogen. However, there is limited information about the potential contribution of LT-A to development of protective immunity. In the current study, we evaluate the immune response against the A-subunit of LT as well as the A-subunit's potential as a protective antigen when administered alone or in combination with the B-subunit of LT. We evaluated human sera from individuals challenged with a prototypic wild-type ETEC strain as well as sera from individuals living in an ETEC endemic area for the presence of anti-LT, anti-LT-A and anti-LT-B antibodies. In both cases, a significant number of individuals intentionally or endemically infected with ETEC developed antibodies against both LT subunits. In addition, animals immunized with the recombinant proteins developed robust antibody responses that were able to neutralize the enterotoxic and cytotoxic effects of native LT by blocking binding and entry into cells (anti-LT-B) or the intracellular enzymatic activity of the toxin (anti-LT-A). Moreover, antibodies to both LT subunits acted synergistically to neutralize the holotoxin when combined. Taken together, these data support the inclusion of both LT-A and LT-B in prospective vaccines against ETEC.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Bacterial - blood</subject><subject>Antibodies, Bacterial - immunology</subject><subject>Antibodies, Neutralizing - blood</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Antigens</subject><subject>Antigens, Bacterial - genetics</subject><subject>Antigens, Bacterial - immunology</subject><subject>Bacteria</subject><subject>Bacterial Toxins - chemistry</subject><subject>Bacterial Toxins - genetics</subject><subject>Bacterial Toxins - immunology</subject><subject>Binding</subject><subject>Cell Line</subject><subject>Children</subject><subject>Cholera</subject><subject>Cognitive ability</subject><subject>Colonization</subject><subject>Cytotoxicity</subject><subject>Diarrhea</subject><subject>Disease Models, Animal</subject><subject>E coli</subject><subject>Enterotoxigenic Escherichia coli - genetics</subject><subject>Enterotoxigenic Escherichia coli - immunology</subject><subject>Enterotoxins - chemistry</subject><subject>Enterotoxins - genetics</subject><subject>Enterotoxins - immunology</subject><subject>Enzymatic activity</subject><subject>Epidemiology</subject><subject>Escherichia coli</subject><subject>Escherichia coli Infections - epidemiology</subject><subject>Escherichia coli Infections - immunology</subject><subject>Escherichia coli Infections - prevention & control</subject><subject>Escherichia coli Proteins - chemistry</subject><subject>Escherichia coli Proteins - genetics</subject><subject>Escherichia coli Proteins - immunology</subject><subject>Heat</subject><subject>Heat-labile enterotoxin</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunity</subject><subject>Immunity, Mucosal</subject><subject>Immunization</subject><subject>Immunogenicity</subject><subject>Immunoglobulins</subject><subject>Immunology</subject><subject>Infections</subject><subject>Lymphocytes B</subject><subject>Malnutrition</subject><subject>Mice</subject><subject>Morbidity</subject><subject>Mucous Membrane - immunology</subject><subject>Mucous Membrane - microbiology</subject><subject>Neutralization Tests</subject><subject>Patients</subject><subject>Protective antigen</subject><subject>Protein Subunits - genetics</subject><subject>Protein Subunits - immunology</subject><subject>Proteins</subject><subject>Small intestine</subject><subject>Studies</subject><subject>Thermal stability</subject><subject>Tropical diseases</subject><subject>Vaccines</subject><subject>Vibrio cholerae</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptkl2LEzEUhgdR3HX1H4gGvOleTM3nfNwIpYxuoaBgvQ6ZzJk2ZZrUJFP0V_iXTT922RWvkrznPU_yhpNlbwmeElaSj1s3equG6d5ZmGLCCobps-ya1IzmBcXs-aP9VfYqhC3GglVF8TK7osksyppdZ3-agxpGFY1do7gBNMu_j-1oTUSuPwl3oGK-VK0ZAK3cL2PRZLm6RbOAlEWL3W60bg02HTqk0DfvIuhoDglkozkWZmtlbIiosRFSNRGSajRqgt6AN3pjFNJuMGjSrJr57evsRa-GAG8u603243Ozmt_ly69fFvPZMteCFjEXRNS1UlUNbd8RURJKK1X0RFVMiJ5SLUpKO4U1B8qgTFpZUMErrgFqTDC7yd6fufvBBXn5yyBJiStRlCUTybE4OzqntnLvzU7539IpI0-C82upfDR6ANkntqgAF7yiXNC6Jl3LS1CC84Lrtk-sT5fbxnYHnQYbvRqeQJ9WrNnItTtILnhNK5YAkwvAu58jhCh3JmgYBmXBjad3p5AlqY_JPvxj_X86fnZp70Lw0D88hmB5nK_7LnmcL3mZr9T27nGQh6b7gWJ_AVWrzKw</recordid><startdate>20150825</startdate><enddate>20150825</enddate><creator>Norton, Elizabeth B</creator><creator>Branco, Luis M</creator><creator>Clements, John D</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150825</creationdate><title>Evaluating the A-Subunit of the Heat-Labile Toxin (LT) As an Immunogen and a Protective Antigen Against Enterotoxigenic Escherichia coli (ETEC)</title><author>Norton, Elizabeth B ; Branco, Luis M ; Clements, John D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-51599aa89ebfd1571228a6f1a8355f22c5722da0c4e23e755f7625484cee90103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Bacterial - blood</topic><topic>Antibodies, Bacterial - immunology</topic><topic>Antibodies, Neutralizing - blood</topic><topic>Antibodies, Neutralizing - immunology</topic><topic>Antigens</topic><topic>Antigens, Bacterial - genetics</topic><topic>Antigens, Bacterial - immunology</topic><topic>Bacteria</topic><topic>Bacterial Toxins - chemistry</topic><topic>Bacterial Toxins - genetics</topic><topic>Bacterial Toxins - immunology</topic><topic>Binding</topic><topic>Cell Line</topic><topic>Children</topic><topic>Cholera</topic><topic>Cognitive ability</topic><topic>Colonization</topic><topic>Cytotoxicity</topic><topic>Diarrhea</topic><topic>Disease Models, Animal</topic><topic>E coli</topic><topic>Enterotoxigenic Escherichia coli - genetics</topic><topic>Enterotoxigenic Escherichia coli - immunology</topic><topic>Enterotoxins - chemistry</topic><topic>Enterotoxins - genetics</topic><topic>Enterotoxins - immunology</topic><topic>Enzymatic activity</topic><topic>Epidemiology</topic><topic>Escherichia coli</topic><topic>Escherichia coli Infections - epidemiology</topic><topic>Escherichia coli Infections - immunology</topic><topic>Escherichia coli Infections - prevention & control</topic><topic>Escherichia coli Proteins - chemistry</topic><topic>Escherichia coli Proteins - genetics</topic><topic>Escherichia coli Proteins - immunology</topic><topic>Heat</topic><topic>Heat-labile enterotoxin</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunity</topic><topic>Immunity, Mucosal</topic><topic>Immunization</topic><topic>Immunogenicity</topic><topic>Immunoglobulins</topic><topic>Immunology</topic><topic>Infections</topic><topic>Lymphocytes B</topic><topic>Malnutrition</topic><topic>Mice</topic><topic>Morbidity</topic><topic>Mucous Membrane - immunology</topic><topic>Mucous Membrane - microbiology</topic><topic>Neutralization Tests</topic><topic>Patients</topic><topic>Protective antigen</topic><topic>Protein Subunits - genetics</topic><topic>Protein Subunits - immunology</topic><topic>Proteins</topic><topic>Small intestine</topic><topic>Studies</topic><topic>Thermal stability</topic><topic>Tropical diseases</topic><topic>Vaccines</topic><topic>Vibrio cholerae</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Norton, Elizabeth B</creatorcontrib><creatorcontrib>Branco, Luis M</creatorcontrib><creatorcontrib>Clements, John D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Norton, Elizabeth B</au><au>Branco, Luis M</au><au>Clements, John D</au><au>Mantis, Nicholas J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluating the A-Subunit of the Heat-Labile Toxin (LT) As an Immunogen and a Protective Antigen Against Enterotoxigenic Escherichia coli (ETEC)</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-08-25</date><risdate>2015</risdate><volume>10</volume><issue>8</issue><spage>e0136302</spage><epage>e0136302</epage><pages>e0136302-e0136302</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Diarrheal illness contributes to malnutrition, stunted growth, impaired cognitive development, and high morbidity rates in children worldwide. Enterotoxigenic Escherichia coli (ETEC) is a major contributor to this diarrheal disease burden. ETEC cause disease in the small intestine by means of colonization factors and by production of a heat-labile enterotoxin (LT) and/or a small non-immunogenic heat-stable enterotoxin (ST). Overall, the majority of ETEC produce both ST and LT. LT induces secretion via an enzymatically active A-subunit (LT-A) and a pentameric, cell-binding B-subunit (LT-B). The importance of anti-LT antibodies has been demonstrated in multiple clinical and epidemiological studies, and a number of potential ETEC vaccine candidates have included LT-B as an important immunogen. However, there is limited information about the potential contribution of LT-A to development of protective immunity. In the current study, we evaluate the immune response against the A-subunit of LT as well as the A-subunit's potential as a protective antigen when administered alone or in combination with the B-subunit of LT. We evaluated human sera from individuals challenged with a prototypic wild-type ETEC strain as well as sera from individuals living in an ETEC endemic area for the presence of anti-LT, anti-LT-A and anti-LT-B antibodies. In both cases, a significant number of individuals intentionally or endemically infected with ETEC developed antibodies against both LT subunits. In addition, animals immunized with the recombinant proteins developed robust antibody responses that were able to neutralize the enterotoxic and cytotoxic effects of native LT by blocking binding and entry into cells (anti-LT-B) or the intracellular enzymatic activity of the toxin (anti-LT-A). Moreover, antibodies to both LT subunits acted synergistically to neutralize the holotoxin when combined. Taken together, these data support the inclusion of both LT-A and LT-B in prospective vaccines against ETEC.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26305793</pmid><doi>10.1371/journal.pone.0136302</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1708567735 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Antibodies Antibodies, Bacterial - blood Antibodies, Bacterial - immunology Antibodies, Neutralizing - blood Antibodies, Neutralizing - immunology Antigens Antigens, Bacterial - genetics Antigens, Bacterial - immunology Bacteria Bacterial Toxins - chemistry Bacterial Toxins - genetics Bacterial Toxins - immunology Binding Cell Line Children Cholera Cognitive ability Colonization Cytotoxicity Diarrhea Disease Models, Animal E coli Enterotoxigenic Escherichia coli - genetics Enterotoxigenic Escherichia coli - immunology Enterotoxins - chemistry Enterotoxins - genetics Enterotoxins - immunology Enzymatic activity Epidemiology Escherichia coli Escherichia coli Infections - epidemiology Escherichia coli Infections - immunology Escherichia coli Infections - prevention & control Escherichia coli Proteins - chemistry Escherichia coli Proteins - genetics Escherichia coli Proteins - immunology Heat Heat-labile enterotoxin Humans Immune response Immune system Immunity Immunity, Mucosal Immunization Immunogenicity Immunoglobulins Immunology Infections Lymphocytes B Malnutrition Mice Morbidity Mucous Membrane - immunology Mucous Membrane - microbiology Neutralization Tests Patients Protective antigen Protein Subunits - genetics Protein Subunits - immunology Proteins Small intestine Studies Thermal stability Tropical diseases Vaccines Vibrio cholerae |
| title | Evaluating the A-Subunit of the Heat-Labile Toxin (LT) As an Immunogen and a Protective Antigen Against Enterotoxigenic Escherichia coli (ETEC) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T22%3A32%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Evaluating%20the%20A-Subunit%20of%20the%20Heat-Labile%20Toxin%20(LT)%20As%20an%20Immunogen%20and%20a%20Protective%20Antigen%20Against%20Enterotoxigenic%20Escherichia%20coli%20(ETEC)&rft.jtitle=PloS%20one&rft.au=Norton,%20Elizabeth%20B&rft.date=2015-08-25&rft.volume=10&rft.issue=8&rft.spage=e0136302&rft.epage=e0136302&rft.pages=e0136302-e0136302&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0136302&rft_dat=%3Cproquest_plos_%3E3793736701%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1708567735&rft_id=info:pmid/26305793&rft_doaj_id=oai_doaj_org_article_f62558e06482452991db47ea54464cbf&rfr_iscdi=true |