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Clin. Vaccine Immunol. doi:10.1128/CVI.00050-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

IMMUNOLOGICAL EVIDENCE FOR FUNCTIONAL vs. STRUCTURAL MIMICRY WITH A Shigella flexneri Y POLYSACCHARIDE-MIMETIC PEPTIDE

Department of Chemistry, Simon Fraser University, Burnaby, B.C.,Canada V5A 1S6

^* To whom correspondence should be addressed. Email: bpinto{at}sfu.ca.

	Abstract

An approach to vaccine design is the use of molecules that mimic the immunogenic element of interest. In this context, the interaction of MDWNMHAA, a peptide mimic of the Shigella flexneri Y O-polysaccharide, with an anti-carbohydrate monoclonal antibody, as studied previously by X-ray crystallography, suggested the presence of functional vs. structural mimicry, and a bound peptide conformation that was not represented significantly in the free-ligand ensemble. The antibody response elicited by a MDWNMHAA-carrier protein (tetanus toxoid, TT) conjugate has now been investigated in BALB/c mice. Mice were immunized following an homologous prime/boost strategy using MDWNMHAA-TT as immunogen. Mice showed anti-peptide antibody (IgG) titers that increased after boosting. High anti-LPS (IgG) titers were observed after the last boost. A faster immune response, with cross-reactive titers, was observed with a peptide conjugate with 30% more copies of peptide. The binding of anti-peptide polyclonal antibodies to LPS could be inhibited by LPS, polysaccharide (PS), MDWNMHAA and MDWNMHAA-BSA, as assessed by inhibition ELISA. Conversely, mice immunized with PS-TT showed IgG anti-peptide titers. These data demonstrate the cross-reactivity of the antibody response and support the hypothesis that functional as opposed to structural mimicry of the S. flexneri Y O-polysaccharide by MDWNMHAA or the underrepresentation of the bound ligand conformation in the free-ligand ensemble does not compromise immunological cross-reactivity.

Prime/boost strategies were performed with an heterologous boost of PS-TT or MDWNMHAA-TT. They led to high anti-LPS titers after only three injections, suggesting alternatives to improve the immunogenicity of the carbohydrate-mimetic peptide and confirming the antigenic-mimicry.