دورية أكاديمية
أعرض في EDS

Generation and characterization of a live attenuated enterotoxigenic Escherichia coli combination vaccine expressing six colonization factors and heat-labile toxin subunit B.

التفاصيل البيبلوغرافية
العنوان: Generation and characterization of a live attenuated enterotoxigenic Escherichia coli combination vaccine expressing six colonization factors and heat-labile toxin subunit B.
المؤلفون: Turner AK; TD Vaccines A/S, Aspvej 12, Rauf, Skørping 9520, Denmark., Stephens JC, Beavis JC, Greenwood J, Gewert C, Randall R, Freeman D, Darsley MJ
المصدر: Clinical and vaccine immunology : CVI [Clin Vaccine Immunol] 2011 Dec; Vol. 18 (12), pp. 2128-35. Date of Electronic Publication: 2011 Oct 12.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101252125 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1556-679X (Electronic) Linking ISSN: 1556679X NLM ISO Abbreviation: Clin Vaccine Immunol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Society for Microbiology, [2006]-
مواضيع طبية MeSH: Bacterial Toxins/*genetics , Enterotoxigenic Escherichia coli/*genetics , Escherichia coli Vaccines/*genetics , Virulence Factors/*genetics, Bacterial Toxins/immunology ; Enterotoxigenic Escherichia coli/immunology ; Escherichia coli Vaccines/administration & dosage ; Escherichia coli Vaccines/immunology ; Humans ; Plasmids ; Randomized Controlled Trials as Topic ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/genetics ; Vaccines, Attenuated/immunology ; Vaccines, Combined/administration & dosage ; Vaccines, Combined/genetics ; Vaccines, Combined/immunology ; Vaccines, Synthetic/administration & dosage ; Vaccines, Synthetic/genetics ; Vaccines, Synthetic/immunology ; Virulence Factors/immunology
مستخلص: Live attenuated oral enterotoxigenic Escherichia coli (ETEC) vaccines have been demonstrated to be safe and immunogenic in human volunteers and to provide a viable approach to provide protection against this important pathogen. This report describes the construction of new ETEC vaccine candidate strains from recent clinical isolates and their characterization. All known genes for ETEC toxins were removed, and attenuating deletion mutations were made in the aroC, ompC, and ompF chromosomal genes. An isolate expressing coli surface antigen 2 (CS2), CS3, heat-labile toxin (LT), heat-stable toxin (ST), and enteroaggregative Escherichia coli heat-stable toxin 1 (EAST1) was attenuated to generate ACAM2007. The subsequent insertion of the operon encoding CS1 created ACAM2017, and this was further modified by the addition of an expression cassette containing the eltB gene, encoding a pentamer of B subunits of LT (LTB), to generate ACAM2027. Another isolate expressing CS5, CS6, LT, ST, and EAST1 was attenuated to generate ACAM2006, from which a lysogenic prophage was deleted to create ACAM2012 and an LTB gene was introduced to form ACAM2022. Finally, a previously described vaccine strain, ACAM2010, had the eltB gene incorporated to generate ACAM2025. All recombinant genes were incorporated into the chromosomal sites of the attenuating mutations to ensure maximal genetic stability. The expression of the recombinant antigens and the changes in plasmids accompanying the deletion of toxin genes are described. Strains ACAM2025, ACAM2022, and ACAM2027 have been combined to create the ETEC vaccine formulation ACE527, which has recently successfully completed a randomized, double-blind, placebo-controlled phase I trial and is currently undergoing a randomized, double-blind placebo-controlled phase II challenge trial, both in healthy adult volunteers.
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المشرفين على المادة: 0 (Bacterial Toxins)
0 (Escherichia coli Vaccines)
0 (Vaccines, Attenuated)
0 (Vaccines, Combined)
0 (Vaccines, Synthetic)
0 (Virulence Factors)
تواريخ الأحداث: Date Created: 20111014 Date Completed: 20120314 Latest Revision: 20211020
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC3232708
DOI: 10.1128/CVI.05345-11
PMID: 21994355
قاعدة البيانات: MEDLINE
الوصف
تدمد:1556-679X
DOI:10.1128/CVI.05345-11