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Over-expression of major colonization factors of enterotoxigenic Escherichia coli, alone or together, on non-toxigenic E. coli bacteria
University of Gothenburg, Sweden.ORCID iD: 0000-0001-6783-4622
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2010 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 28, no 43, p. 6977-6984Article in journal (Refereed) Published
Abstract [en]

Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrheal disease and deaths among children in developing countries and the major cause of traveller's diarrhea. Since surface protein colonization factors (CFs) of ETEC are important for pathogenicity and immune protection is mainly mediated by locally produced IgA antibodies in the gut, much effort has focused on the development of an oral CF-based vaccine. We have recently described the development of recombinant strains over-expressing CFA/I; the most prevalent CF among human clinical ETEC isolates. Here, non-toxigenic recombinant E. coli strains over-expressing Coli surface antigen 2 (CS2), CS4, CS5, and CS6, either alone, or each in combination with CFA/I were constructed by cloning the genes required for expression and assembly of each CF into expression vectors harboring a strong promoter. Immunological assays showed that recombinant strains expressing single CFs produced those in significantly larger amounts than did corresponding naturally high producing reference strains. Recombinant strains co-expressing CFA/I together with another CF also expressed significantly larger amounts of both CFs compared with the corresponding references strains. Further, when tested in mice, oral immunization with formalin-killed recombinant bacteria co-expressing one such double-expression CF pair, CFA/I. +. CS2, induced specific serum IgG. +. IgM and fecal IgA antibody responses against both CFs exceeding the responses induced by immunizations with natural reference strains expressing CFA/I and CS2, respectively. We conclude that the described type of recombinant bacteria over-expressing major CFs of ETEC, alone or in combination, may be useful as candidate strains for use in an oral whole-cell CF-ETEC vaccine. 

Place, publisher, year, edition, pages
2010. Vol. 28, no 43, p. 6977-6984
Keywords [en]
Anti-colonization immunity, Co-expression, Colonization factors, ETEC, ETEC vaccine, Over-expression, Escherichia coli vaccine, formaldehyde, immunoglobulin A antibody, immunoglobulin G, immunoglobulin M, membrane antigen, membrane protein, protein colonization factor i, surface antigen 2, surface antigen 4, surface antigen 5, surface antigen 6, unclassified drug, animal experiment, animal model, antibody response, article, bacterial strain, controlled study, enterotoxigenic Escherichia coli, Escherichia coli infection, female, gene overexpression, molecular cloning, mouse, nonhuman, nucleotide sequence, priority journal, Animals, Antibodies, Bacterial, Antigens, Bacterial, Escherichia coli Infections, Escherichia coli Proteins, Escherichia coli Vaccines, Fimbriae Proteins, Mice, Mice, Inbred BALB C, Recombinant Proteins, Recombination, Genetic
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Natural Sciences
Identifiers
URN: urn:nbn:se:ri:diva-56879DOI: 10.1016/j.vaccine.2010.08.047Scopus ID: 2-s2.0-77957333788OAI: oai:DiVA.org:ri-56879DiVA, id: diva2:1612585
Note

Funding details: Vetenskapsrådet, VR; Funding details: Sahlgrenska Universitetssjukhuset, SU; Funding details: Marianne and Marcus Wallenberg Foundation, MMW; Funding text 1: This work was supported by grants from the S Research Council (VR), Göteborg University Vaccine Research Institute (GUVAX), Marianne and Marcus Wallenberg foundation, and Sahlgrenska University Hospital (ALF).

Available from: 2021-11-18 Created: 2021-11-18 Last updated: 2021-11-18Bibliographically approved

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Nygren, Erik

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