{'fraction_non_alphanumeric': 0.03485517918507609, 'fraction_numerical': 0.0014727540500736377, 'mean_word_length': 5.309597523219814, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Immunological Evidence for Functional Rather than Structural Mimicry by a Shigella ﬂexneri Y Polysaccharide-Mimetic Peptide (cid:1)

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 per- formed 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.