Shiqi Zhou , Karl O.A. Yu , Moustafa T. Mabrouk , Dushyant Jahagirdar , Wei-Chiao Huang , Julio A. Guerra , Xuedan He , Joaquin Ortega , Steven T. Poole , Eric R. Hall , Oscar G. Gomez-Duarte , Milton Maciel Jr. , Jonathan F. Lovell
{"title":"脂质体显示的重组产肠毒素大肠杆菌(ETEC)定殖抗原诱导小鼠抗体。","authors":"Shiqi Zhou , Karl O.A. Yu , Moustafa T. Mabrouk , Dushyant Jahagirdar , Wei-Chiao Huang , Julio A. Guerra , Xuedan He , Joaquin Ortega , Steven T. Poole , Eric R. Hall , Oscar G. Gomez-Duarte , Milton Maciel Jr. , Jonathan F. Lovell","doi":"10.1016/j.bj.2023.03.001","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Enterotoxigenic <em>Escherichia coli</em> (ETEC) strains cause infectious diarrhea and colonize host intestine epithelia via surface-expressed colonization factors. Colonization factor antigen I (CFA/I), a prevalent ETEC colonization factor, is a vaccine target since antibodies directed to this fimbria can block ETEC adherence and prevent diarrhea.</p></div><div><h3>Methods</h3><p>Two recombinant antigens derived from CFA/I were investigated with a vaccine adjuvant system that displays soluble antigens on the surface of immunogenic liposomes. The first antigen, CfaEB, is a chimeric fusion protein comprising the minor (CfaE) and major (CfaB) subunits of CFA/I. The second, CfaEad, is the adhesin domain of CfaE.</p></div><div><h3>Results</h3><p>Owing to their His-tag, recombinant CfaEB and CfaEad, spontaneously bound upon admixture with nanoliposomes containing cobalt-porphyrin phospholipid (CoPoP), as well as a synthetic monophosphoryl lipid A (PHAD) adjuvant. Intramuscular immunization of mice with sub-microgram doses CfaEB or CfaEad admixed with CoPoP/PHAD liposomes elicited serum IgG and intestinal IgA antibodies. The smaller CfaEad antigen benefitted more from liposome display. Serum and intestine antibodies from mice immunized with liposome-displayed CfaEB or CfaEad recognized native CFA/I fimbria as evidenced by immunofluorescence and hemagglutination inhibition assays using the CFA/I-expressing H10407 ETEC strain.</p></div><div><h3>Conclusion</h3><p>These data show that colonization factor-derived recombinant ETEC antigens exhibit immunogenicity when delivered in immunogenic particle-based formulations.</p></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"46 6","pages":"Article 100588"},"PeriodicalIF":4.1000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2319417023000252/pdfft?md5=77fff00d3445a8c813d9d2729eeb34d7&pid=1-s2.0-S2319417023000252-main.pdf","citationCount":"3","resultStr":"{\"title\":\"Antibody induction in mice by liposome-displayed recombinant enterotoxigenic Escherichia coli (ETEC) colonization antigens\",\"authors\":\"Shiqi Zhou , Karl O.A. Yu , Moustafa T. Mabrouk , Dushyant Jahagirdar , Wei-Chiao Huang , Julio A. Guerra , Xuedan He , Joaquin Ortega , Steven T. Poole , Eric R. Hall , Oscar G. Gomez-Duarte , Milton Maciel Jr. , Jonathan F. Lovell\",\"doi\":\"10.1016/j.bj.2023.03.001\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Enterotoxigenic <em>Escherichia coli</em> (ETEC) strains cause infectious diarrhea and colonize host intestine epithelia via surface-expressed colonization factors. Colonization factor antigen I (CFA/I), a prevalent ETEC colonization factor, is a vaccine target since antibodies directed to this fimbria can block ETEC adherence and prevent diarrhea.</p></div><div><h3>Methods</h3><p>Two recombinant antigens derived from CFA/I were investigated with a vaccine adjuvant system that displays soluble antigens on the surface of immunogenic liposomes. The first antigen, CfaEB, is a chimeric fusion protein comprising the minor (CfaE) and major (CfaB) subunits of CFA/I. The second, CfaEad, is the adhesin domain of CfaE.</p></div><div><h3>Results</h3><p>Owing to their His-tag, recombinant CfaEB and CfaEad, spontaneously bound upon admixture with nanoliposomes containing cobalt-porphyrin phospholipid (CoPoP), as well as a synthetic monophosphoryl lipid A (PHAD) adjuvant. Intramuscular immunization of mice with sub-microgram doses CfaEB or CfaEad admixed with CoPoP/PHAD liposomes elicited serum IgG and intestinal IgA antibodies. The smaller CfaEad antigen benefitted more from liposome display. Serum and intestine antibodies from mice immunized with liposome-displayed CfaEB or CfaEad recognized native CFA/I fimbria as evidenced by immunofluorescence and hemagglutination inhibition assays using the CFA/I-expressing H10407 ETEC strain.</p></div><div><h3>Conclusion</h3><p>These data show that colonization factor-derived recombinant ETEC antigens exhibit immunogenicity when delivered in immunogenic particle-based formulations.</p></div>\",\"PeriodicalId\":8934,\"journal\":{\"name\":\"Biomedical Journal\",\"volume\":\"46 6\",\"pages\":\"Article 100588\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2023-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2319417023000252/pdfft?md5=77fff00d3445a8c813d9d2729eeb34d7&pid=1-s2.0-S2319417023000252-main.pdf\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomedical Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2319417023000252\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Journal","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2319417023000252","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Antibody induction in mice by liposome-displayed recombinant enterotoxigenic Escherichia coli (ETEC) colonization antigens
Background
Enterotoxigenic Escherichia coli (ETEC) strains cause infectious diarrhea and colonize host intestine epithelia via surface-expressed colonization factors. Colonization factor antigen I (CFA/I), a prevalent ETEC colonization factor, is a vaccine target since antibodies directed to this fimbria can block ETEC adherence and prevent diarrhea.
Methods
Two recombinant antigens derived from CFA/I were investigated with a vaccine adjuvant system that displays soluble antigens on the surface of immunogenic liposomes. The first antigen, CfaEB, is a chimeric fusion protein comprising the minor (CfaE) and major (CfaB) subunits of CFA/I. The second, CfaEad, is the adhesin domain of CfaE.
Results
Owing to their His-tag, recombinant CfaEB and CfaEad, spontaneously bound upon admixture with nanoliposomes containing cobalt-porphyrin phospholipid (CoPoP), as well as a synthetic monophosphoryl lipid A (PHAD) adjuvant. Intramuscular immunization of mice with sub-microgram doses CfaEB or CfaEad admixed with CoPoP/PHAD liposomes elicited serum IgG and intestinal IgA antibodies. The smaller CfaEad antigen benefitted more from liposome display. Serum and intestine antibodies from mice immunized with liposome-displayed CfaEB or CfaEad recognized native CFA/I fimbria as evidenced by immunofluorescence and hemagglutination inhibition assays using the CFA/I-expressing H10407 ETEC strain.
Conclusion
These data show that colonization factor-derived recombinant ETEC antigens exhibit immunogenicity when delivered in immunogenic particle-based formulations.
期刊介绍：
Biomedical Journal publishes 6 peer-reviewed issues per year in all fields of clinical and biomedical sciences for an internationally diverse authorship. Unlike most open access journals, which are free to readers but not authors, Biomedical Journal does not charge for subscription, submission, processing or publication of manuscripts, nor for color reproduction of photographs.
Clinical studies, accounts of clinical trials, biomarker studies, and characterization of human pathogens are within the scope of the journal, as well as basic studies in model species such as Escherichia coli, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealing the function of molecules, cells, and tissues relevant for human health. However, articles on other species can be published if they contribute to our understanding of basic mechanisms of biology.
A highly-cited international editorial board assures timely publication of manuscripts. Reviews on recent progress in biomedical sciences are commissioned by the editors.
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