A totally synthetic lipopeptide-based self-adjuvanting vaccine induces neutralizing antibodies against heat-stable enterotoxin from enterotoxigenic Escherichia coli.

ST-based lipopeptide vaccine candidates were constructed in which ST was chemically synthesized and folded into the correct conformation prior to ligation to a module containing a T-helper cell epitope (T(H)) and the Toll-like receptor 2 (TLR2) agonist, S-[2,3-bis(palmitoyloxy)propyl]cysteine (P2C). Two different chemistries, thioether-based and oxime-based, were then used to ligate ST to the lipidated T(H) epitope. The enterotoxic activity of synthetic ST and the ST-based lipopeptide vaccines was determined in mice followed by an evaluation of immunological efficacy. The importance of the fine detail in chemical composition used in vaccine design was demonstrated by the findings that (i) the oxime-based vaccine exhibited little or no toxicity but the thioether-based vaccine, exhibited residual toxicity in suckling mice, (ii) although each of the synthetic vaccines generated specific anti-ST antibodies, it was the low titer antibodies induced by the oxime-based vaccine that demonstrated better neutralizing activity suggesting that the chemical linkage also affects the specificity of antibodies, (iii) the geometric arrangement of ST within a vaccine can profoundly affect the specificity and biological function of the antibodies that are elicited, and (iv) the lipopeptide-based ST vaccine candidate assembled using oxime chemistry induced a better neutralizing antibody response to ST when administered by the mucosal (intranasal) route.

Concise synthesis of the pentasaccharide O-antigen of Escherichia coli O83:K24:H31 present in the Colinfant vaccine.

A block synthetic approach is presented for the synthesis of the pentasaccharide repeating unit of the O-antigen of E. coli O83:K24:H31 strain, present in the "Colifant" vaccine. The target pentasaccharide has been synthesized by coupling a disaccharide with a trisaccharide in excellent yield. Yields are quite satisfactory in all intermediate steps.

Extraintestinal isolates of Escherichia coli: identification and prospects for vaccine development.

Extraintestinal pathogenic Escherichia coli (ExPEC) cause a wide variety of infections that are responsible for significant morbidity, mortality and costs to our healthcare system. Thereby, the development of an efficacious ExPEC vaccine will minimize disease and may be cost-effective in selected patient groups. Surface polysaccharides, such as capsule, have been traditional targets for vaccine development. Considering that significant antigenic heterogeneity exists among surface polysaccharides present in various ExPEC strains, their use as vaccine candidates will be challenging. Therefore, alternative vaccine candidates/approaches are being identified and evaluated and are discussed in this review. The authors envision that an efficacious ExPEC vaccine will consist of either a polyvalent subunit vaccine or a genetically engineered killed whole-cell vaccine.