Construction of Synthetic Immunogens in View of Developing Orally-Active Anti-Enterotoxigenic E. coli Vaccines.

摘要

The aim of this research was to build immunogens susceptible of inducing a response against enterotoxigenic E. coli (Escherichia coli) (ETEC) following oral administration. The antigenic determinants were peptides copying structures of the colonization factor antigens (CFA), the carriers were either the Beta-chain of cholera toxin or a synthetic copy of one of its fragment. This fragment is known to bind in the Payer's patches the GM1 ganglioside which represents the toxin receptor. Two different E. coli peptides have been analyzed by HPLC (high performance liquid chromatography). Eight different conjugates have been prepared using glutaraldehyde or carbodiimide. The two peptides have been linked to muramyl dipeptide-Lys, 6-0-succinyl murabutide, Beta-chain of cholera toxin and the GM1 ganglioside binding peptide. After analysis, these conjugates have been sent to Dr. Reid to be tested in in vitro systems. They have been administered to mice orally. The antibody response has been studied in sera. Only a slight anti-Beta-cholera toxin response has been obtained. It would be advisable to increase the dosage of immunogens. Keywords: 1-Orally-active vaccines, 2-Synthetic enterotoxigenic E. coli immunogens, 3-Muramyl dipeptides, 4-Synthetic cholera toxin receptor, 5-GM1 ganglioside, RA 1. (jg)