Recombinant cholera toxin B subunit and gene fusion proteins for oral vaccination.

The B subunit portion of cholera toxin (CTB) is a safe and effective oral immunizing agent in humans, affording protection against both cholera and diarrhoea caused by enterotoxigenic Escherichia coli producing heat-labile toxin (LT) (Clemens et al., 1986; 1988). CTB may also be used as a carrier of various "foreign" antigens suitable for oral administration. To facilitate large-scale production of CTB for vaccine development purposes, we have constructed recombinant overexpression systems for CTB proteins in which the CTB gene is under the control of strong foreign (non-cholera) promoters and in which it is also possible to fuse oligonucleotides to the CTB gene and thereby achieve overexpression of hybrid proteins (Sanchez and Holmgren, 1989; Sanchez et al., 1988). We here expand these findings by describing overexpression of CTB by a constitutive tacP promoter as well as by the T7 RNA-polymerase promoter, and also by describing gene fusions leading to overexpression of several hybrid proteins between heat-stable E. coli enterotoxin (STa)-related peptides to either the amino or carboxy ends of CTB. Each of the hybrid proteins, when tested as immunogens in rabbits, stimulated significant anti-STa as well as anti-CTB antibody formation, although the anti-STa antibody levels attained (c.a. 1-15 micrograms/ml specific anti-STa immunoglobulin) were too low to give more than partial neutralization of STa intestinal challenge in baby mice. The hybrid proteins also had a near-native conformation, as apparent from their oligomeric nature and their strong reactivity with both a neutralizing antibody against the B subunit and a neutralizing monoclonal antibody (mAb) against STa.(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsJ Sanchez, S Johansson, B Löwenadler, A M Svennerholm, J Holmgren
JournalResearch in microbiology (Res Microbiol) 1990 Sep-Oct Vol. 141 Issue 7-8 Pg. 971-9 ISSN: 0923-2508 [Print] FRANCE
PMID2101488 (Publication Type: Journal Article)
Chemical References
  • Antibodies, Bacterial
  • Cholera Vaccines
  • Recombinant Fusion Proteins
  • Vaccines, Synthetic
  • Cholera Toxin
  • Administration, Oral
  • Amino Acid Sequence
  • Animals
  • Antibodies, Bacterial (biosynthesis)
  • Cholera Toxin (genetics, immunology)
  • Cholera Vaccines (administration & dosage, genetics, isolation & purification)
  • Molecular Sequence Data
  • Rabbits
  • Recombinant Fusion Proteins (genetics, immunology)
  • Vaccines, Synthetic (administration & dosage, genetics, isolation & purification)

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