From Epitope Characterization to the Design of Semisynthetic Glycoconjugate Vaccines against Shigella flexneri 2a Infection

摘要

The four-step conception of a potential Shigella flexneri 2a glycoconjugate vaccine exposing synthetic oligosaccharides mimicking the serotype-specific protective determinants is described. (i) Study of the recognition of synthetic 0-antigen fragments by protective murine mIgGs showed that the 0-antigen exhibits a serotype-specific immunodominant epitope and that chain elongation improves binding. (ii) Five epitoperelated tri- to pentadecasaccharides were synthesized and coupled via single point-attachment to tetanus toxoid or PADRE. (iii) The immunogenicity of the conjugates was assessed in mice. (iv) The protective efficacy of sera induced by the most immunogenic conjugates was evaluated in amurine model of pulmonary infection. A pentadecasaccharide was identified as a good candidate for further development of a S. flexneri 2a semi-synthetic glycoconjugate vaccine.