Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen) and a toxoid fusion of heat-stable toxin (STa) and heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC) retain broad anti-CFA and antitoxin antigenicity

Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunol...

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Veröffentlicht in:PloS one 2015-03, Vol.10 (3), p.e0121623
Hauptverfasser: Ruan, Xiaosai, Sack, David A, Zhang, Weiping
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description Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent vaccine development.
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Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent vaccine development.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0121623</identifier><identifier>PMID: 25803825</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adults ; Animals ; Antibodies ; Antibodies, Bacterial - blood ; Antigenic determinants ; Antigenicity ; Antigens ; Antigens, Bacterial - immunology ; Artificial Gene Fusion - methods ; Bacteria ; Bacterial Toxins - genetics ; Bacterial Toxins - toxicity ; Bacterial Vaccines ; Cholera ; Colonization ; Colonization factor ; Consortia ; Developing countries ; Diarrhea ; Drug dosages ; E coli ; Enterotoxigenic Escherichia coli - genetics ; Enterotoxigenic Escherichia coli - metabolism ; Enterotoxins ; Enterotoxins - genetics ; Enterotoxins - toxicity ; Epitopes ; Escherichia coli ; Escherichia coli Proteins - genetics ; Escherichia coli Proteins - toxicity ; Fimbriae Proteins - genetics ; Fimbriae Proteins - immunology ; Genetic research ; Health aspects ; Heat ; Immunity ; Immunization ; Immunogenicity ; Immunoglobulins ; Immunology ; Laboratory animals ; LDCs ; Mice ; Neutralization ; Neutralization Tests ; Strains (organisms) ; Suidae ; Thermal stability ; Toxins ; Vaccine development ; Vaccines ; Veterinary colleges ; Veterinary medicine ; Wildlife conservation</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0121623</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Ruan 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 Ruan et al 2015 Ruan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c524t-79501f7755b8c6398b2da972458662a4f9c35387b6d41f4777f8ee2437d506b53</citedby><cites>FETCH-LOGICAL-c524t-79501f7755b8c6398b2da972458662a4f9c35387b6d41f4777f8ee2437d506b53</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/PMC4372207/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372207/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25803825$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ruan, Xiaosai</creatorcontrib><creatorcontrib>Sack, David A</creatorcontrib><creatorcontrib>Zhang, Weiping</creatorcontrib><title>Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen) and a toxoid fusion of heat-stable toxin (STa) and heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC) retain broad anti-CFA and antitoxin antigenicity</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. 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This MEFA strategy may be generally used in multivalent vaccine development.</description><subject>Adults</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Bacterial - blood</subject><subject>Antigenic determinants</subject><subject>Antigenicity</subject><subject>Antigens</subject><subject>Antigens, Bacterial - immunology</subject><subject>Artificial Gene Fusion - methods</subject><subject>Bacteria</subject><subject>Bacterial Toxins - genetics</subject><subject>Bacterial Toxins - toxicity</subject><subject>Bacterial Vaccines</subject><subject>Cholera</subject><subject>Colonization</subject><subject>Colonization factor</subject><subject>Consortia</subject><subject>Developing countries</subject><subject>Diarrhea</subject><subject>Drug dosages</subject><subject>E coli</subject><subject>Enterotoxigenic Escherichia coli - genetics</subject><subject>Enterotoxigenic Escherichia coli - metabolism</subject><subject>Enterotoxins</subject><subject>Enterotoxins - genetics</subject><subject>Enterotoxins - toxicity</subject><subject>Epitopes</subject><subject>Escherichia coli</subject><subject>Escherichia coli Proteins - genetics</subject><subject>Escherichia coli Proteins - toxicity</subject><subject>Fimbriae Proteins - genetics</subject><subject>Fimbriae Proteins - immunology</subject><subject>Genetic research</subject><subject>Health aspects</subject><subject>Heat</subject><subject>Immunity</subject><subject>Immunization</subject><subject>Immunogenicity</subject><subject>Immunoglobulins</subject><subject>Immunology</subject><subject>Laboratory animals</subject><subject>LDCs</subject><subject>Mice</subject><subject>Neutralization</subject><subject>Neutralization Tests</subject><subject>Strains (organisms)</subject><subject>Suidae</subject><subject>Thermal stability</subject><subject>Toxins</subject><subject>Vaccine development</subject><subject>Vaccines</subject><subject>Veterinary colleges</subject><subject>Veterinary medicine</subject><subject>Wildlife conservation</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>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNp1UsuO0zAUjRCIGQb-AIElJNQu0vqRxMkGqaraoVIRCwpb6yZxWleeuNgOYj6Zv8Bp0mFmgWQpts8jx_feKHpL8IwwTuZH09kW9OxkWjnDhJKMsmfRNSkYjTOK2fNH-6volXNHjFOWZ9nL6IqmOWY5Ta-jP7eylV5VqOmcMq1DpkGAluvFfDPfhPUDfVmtF2hy12mv5El5c5IjF0Hr1V6207Cpg8ib30bVFzD4HCT42HkotexB1aLJtx0M9DOmoVT_sO1u2qtk66U1_V3wDsFWrjpIq6qDAlQZrdBktVstp8hKD0FWWgP1OUocUg9RwmHwHBOqSvn719GLBrSTb8bvTfR9vdotP8fbr7eb5WIbVylNfMyLFJOG8zQt8ypjRV7SGgpOkzSUjkLSFBULZeRlViekSTjnTS4lTRivU5yVKbuJ3g--J22cGLvkBMmyjOGCMxwYm4FRGziKk1V3YO-FASXOF8buBdjQEy0FoQzqguGE5yQhUAKHkuAil7wgFW5k8Po0_q0r72RdhepZ0E9MnyKtOoi9-SVCYEoxDwYfRgNrfnbS-f9E_jiw9hBSheZpf3BGd76fGbFIKGUc85wFYjIQK2ucs7J5iEKw6Of2Yi_6uRXj3AbZu8fPeBBdBpX9BQxp6yk</recordid><startdate>20150324</startdate><enddate>20150324</enddate><creator>Ruan, Xiaosai</creator><creator>Sack, David A</creator><creator>Zhang, Weiping</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>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150324</creationdate><title>Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen) and a toxoid fusion of heat-stable toxin (STa) and heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC) retain broad anti-CFA and antitoxin antigenicity</title><author>Ruan, Xiaosai ; Sack, David A ; Zhang, Weiping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c524t-79501f7755b8c6398b2da972458662a4f9c35387b6d41f4777f8ee2437d506b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adults</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Bacterial - blood</topic><topic>Antigenic determinants</topic><topic>Antigenicity</topic><topic>Antigens</topic><topic>Antigens, Bacterial - immunology</topic><topic>Artificial Gene Fusion - methods</topic><topic>Bacteria</topic><topic>Bacterial Toxins - genetics</topic><topic>Bacterial Toxins - toxicity</topic><topic>Bacterial Vaccines</topic><topic>Cholera</topic><topic>Colonization</topic><topic>Colonization factor</topic><topic>Consortia</topic><topic>Developing countries</topic><topic>Diarrhea</topic><topic>Drug dosages</topic><topic>E coli</topic><topic>Enterotoxigenic Escherichia coli - genetics</topic><topic>Enterotoxigenic Escherichia coli - metabolism</topic><topic>Enterotoxins</topic><topic>Enterotoxins - genetics</topic><topic>Enterotoxins - toxicity</topic><topic>Epitopes</topic><topic>Escherichia coli</topic><topic>Escherichia coli Proteins - genetics</topic><topic>Escherichia coli Proteins - toxicity</topic><topic>Fimbriae Proteins - genetics</topic><topic>Fimbriae Proteins - immunology</topic><topic>Genetic research</topic><topic>Health aspects</topic><topic>Heat</topic><topic>Immunity</topic><topic>Immunization</topic><topic>Immunogenicity</topic><topic>Immunoglobulins</topic><topic>Immunology</topic><topic>Laboratory animals</topic><topic>LDCs</topic><topic>Mice</topic><topic>Neutralization</topic><topic>Neutralization Tests</topic><topic>Strains (organisms)</topic><topic>Suidae</topic><topic>Thermal stability</topic><topic>Toxins</topic><topic>Vaccine development</topic><topic>Vaccines</topic><topic>Veterinary colleges</topic><topic>Veterinary medicine</topic><topic>Wildlife conservation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ruan, Xiaosai</creatorcontrib><creatorcontrib>Sack, David A</creatorcontrib><creatorcontrib>Zhang, Weiping</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>Proquest Nursing &amp; Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological &amp; Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest 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 &amp; Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies &amp; Aerospace Collection</collection><collection>Agricultural &amp; Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest 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</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 &amp; Medical Complete (Alumni)</collection><collection>ProQuest Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - 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Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent vaccine development.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25803825</pmid><doi>10.1371/journal.pone.0121623</doi><oa>free_for_read</oa></addata></record>
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1932-6203
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subjects Adults
Animals
Antibodies
Antibodies, Bacterial - blood
Antigenic determinants
Antigenicity
Antigens
Antigens, Bacterial - immunology
Artificial Gene Fusion - methods
Bacteria
Bacterial Toxins - genetics
Bacterial Toxins - toxicity
Bacterial Vaccines
Cholera
Colonization
Colonization factor
Consortia
Developing countries
Diarrhea
Drug dosages
E coli
Enterotoxigenic Escherichia coli - genetics
Enterotoxigenic Escherichia coli - metabolism
Enterotoxins
Enterotoxins - genetics
Enterotoxins - toxicity
Epitopes
Escherichia coli
Escherichia coli Proteins - genetics
Escherichia coli Proteins - toxicity
Fimbriae Proteins - genetics
Fimbriae Proteins - immunology
Genetic research
Health aspects
Heat
Immunity
Immunization
Immunogenicity
Immunoglobulins
Immunology
Laboratory animals
LDCs
Mice
Neutralization
Neutralization Tests
Strains (organisms)
Suidae
Thermal stability
Toxins
Vaccine development
Vaccines
Veterinary colleges
Veterinary medicine
Wildlife conservation
title Genetic fusions of a CFA/I/II/IV MEFA (multiepitope fusion antigen) and a toxoid fusion of heat-stable toxin (STa) and heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC) retain broad anti-CFA and antitoxin antigenicity
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