Construction and expression of immunogenic hybrid enterotoxigenic Escherichia coli CFA/I and CS2 colonization fimbriae for use in vaccines.

Tobias, Joshua,1969Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine (författare)

Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrheal morbidity in developing countries, especially in children and also of traveler's diarrhea. Colonization factors (CFs) of ETEC, like CFA/I and CS2 which are genetically and structurally related, play a substantial role in pathogenicity, and since intestinal-mucosal immune responses against CFs appear to be protective, much effort has focused on the development of a CF-based ETEC vaccine. We have constructed hybrid operons in which the major CS2 subunit-encoding cotA gene was inserted into the CFA/I operon, either replacing (hybrid I) or being added to the major CFA/I subunit-encoding cfaB gene (hybrid II). Using specific monoclonal antibodies against the major subunits of CFA/I and CS2, high levels of surface expression of both fimbrial subunits were shown in E. coli carrying the hybrid II operon. Oral immunization of mice with formalin-killed bacteria expressing hybrid II fimbriae induced strong CFA/I- and CS2-specific serum IgG + IgM and fecal IgA antibody responses, which were higher than those achieved by similar immunization with the reference strains. Bacteria expressing hybrid fimbriae are potential candidate strains in an oral-killed CF-ETEC vaccine, and the approach represents an attractive and novel means of producing a broad-spectrum ETEC vaccine.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Mikrobiologi inom det medicinska området hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Microbiology in the medical area hsv//eng
Amino Acid Sequence
Animals
Enterotoxigenic Escherichia coli
chemistry
genetics
immunology
Escherichia coli Infections
immunology
microbiology
Escherichia coli Proteins
chemistry
genetics
immunology
Escherichia coli Vaccines
chemistry
genetics
immunology
Female
Fimbriae Proteins
chemistry
genetics
immunology
Gene Expression
Humans
Mice
Mice
Inbred BALB C
Molecular Sequence Data
Recombinant Fusion Proteins
chemistry
genetics
immunology
Sequence Alignment

Svennerholm, Ann-Mari,1947Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine(Swepub:gu)xsannx (författare)
Holmgren, Jan,1944Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine(Swepub:gu)xholja (författare)
Lebens, Michael,1956Gothenburg University,Göteborgs universitet,Institutionen för biomedicin,Institute of Biomedicine(Swepub:gu)xlebmi (författare)
Göteborgs universitetInstitutionen för biomedicin (creator_code:org_t)

Ingår i:Applied microbiology and biotechnology: Springer Science and Business Media LLC87:4, s. 1355-651432-06140175-7598

Av författaren/redakt...: Tobias, Joshua, ...; Svennerholm, Ann ...; Holmgren, Jan, 1 ...; Lebens, Michael, ...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Mikrobiologi ino ...

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