Journal
CLINICAL AND VACCINE IMMUNOLOGY
Volume 15, Issue 7, Pages 1106-1114Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/CVI.00050-08
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- Natural Sciences and Engineering Research Council
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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 ( PS), with an anti-carbohydrate monoclonal antibody, as studied previously by X-ray crystallography, suggested the presence of functional rather than structural mimicry and a bound peptide conformation that was not represented significantly in the free-ligand ensemble. The antibody response elicited by an MDWNMHAA-carrier protein ( tetanus toxoid [ TT]) conjugate has now been investigated in BALB/c mice. The mice were immunized following a homologous prime/boost strategy using MDWNMHAA-TT as the immunogen. The mice showed anti-peptide antibody ( immunoglobulin G [IgG]) titers that increased after being boosted. High anti-lipopolysaccharide ( 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 the peptide. The binding of anti-peptide polyclonal antibodies to LPS could be inhibited by LPS, PS, MDWNMHAA, and MDWNMH AA-bovine serum albumin, as assessed by inhibition enzyme- linked immunosorbent assay. 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 PS 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 a 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.
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