Association of MDPs with Synthetic Immunogenic Constructs in View of DevelopingAnti-Enterotoxigenic E. Coli Oral Vaccines

摘要

This study was aimed to design suitable anti-Enterotoxigenic E. Coli (ETEC) oralvaccines using synthetic colonization factor antigen (CPA) and synthetic muramyl peptides (MDP)s. The rationale of this approach was that CPA represent major virulence factors of ETEC and that MDP have been described to enhance the mucosal response. Natural and even more synthetic CPAs are not immunogenic specially when given per os. By combining efficient presentation of the epitopes and suitable immunostimulation, most interesting preclinical results have been obtained. Orally active MDPs administrable to humans have been defined following the establishment of appropriate testing systems. Various parameters of an immune response were chosen to compare systemic versus mucosal response in sera, secretions and different cell populations following immunization per os. The Beta chain of cholera toxin was tested for its capacity of helping an heterogeneous protein administered orally to evoke an immune response. The same Beta chain and a synthetic copy of its GMl binding sequence were used as carriers for the synthetic peptides and one of these peptides was incorporated into microspheres. In all cases, oral administrations were performed and orally active muramyl peptides used as immunoadjuvants. Muramyl peptides were always able to increase the immune responses and under our experimental conditions, already positive results were obtained using the encapsulated peptide administered with MDPs. Antibodies recognizing the immunizing peptide were raised and these antibodies particularly IgAs bound a cognate natural CFAI-ETEC preparation. These data are highly encouraging and suggest that a successful anti-ETEC vaccine could comprise synthetic CPA antigens into microspheres and a selected muramyl peptide.