Development and preclinical evaluation of safety and immunogenicity of an oral ETEC vaccine containing inactivated E. coli bacteria overexpressing colonization factors CFA/I,CS3, CS5 and CS6 combined with a hybrid LT/CT B subunit antigen,administered alone and together with dmLT adjuvant |
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| Authors: | J. Holmgren L. Bourgeois N. Carlin J. Clements B. Gustafsson A. Lundgren E. Nygren J. Tobias R. Walker A.-M. Svennerholm |
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| Affiliation: | 1. University of Gothenburg Vaccine Research Institute (GUVAX), Department of Microbiology and Immunology, University of Gothenburg, Box 435, 405 30 Gothenburg, Sweden;2. PATH, 455 Massachusetts Ave, NW, Washington, DC 20001, USA;3. Etvax AB, Gunnar Asplunds allé, 171 63 Solna, Stockholm, Sweden;4. Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA |
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| Abstract: | A first-generation oral inactivated whole-cell enterotoxigenic Escherichia coli (ETEC) vaccine, comprising formalin-killed ETEC bacteria expressing different colonization factor (CF) antigens combined with cholera toxin B subunit (CTB), when tested in phase III studies did not significantly reduce overall (generally mild) ETEC diarrhea in travelers or children although it reduced more severe ETEC diarrhea in travelers by almost 80%. We have now developed a novel more immunogenic ETEC vaccine based on recombinant non-toxigenic E. coli strains engineered to express increased amounts of CF antigens, including CS6 as well as an ETEC-based B subunit protein (LCTBA), and the optional combination with a nontoxic double-mutant heat-labile toxin (LT) molecule (dmLT) as an adjuvant. |
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| Keywords: | CF, colonization factor CT, cholera toxin B subunit CTB, cholera toxin binding subunit dmLT, double-mutant LT ELISA, enzyme linked immunosorbent assay ETEC, enterotoxigenic Eschericia coli EV, ETEC vaccine GMP, good manufacturing practice i.g. immunization, intragastric immunization LT, heat labile toxin LTB, heat labile toxin binding subunit PV, prototype vaccine |
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