Epitopes described in "Synthesis of a single-molecule L-rhamnose-containing three-component vaccine and evaluation of antigenicity in the presence of anti-L-rhamnose antibodies."

Article Authors:Sourav Sarkar; Steven A Lombardo; Danielle N Herner; Rommel S Talan; Katherine A Wall; Steven J Sucheck
Article Title:Synthesis of a single-molecule L-rhamnose-containing three-component vaccine and evaluation of antigenicity in the presence of anti-L-rhamnose antibodies.
Reference Detail
Reference ID:1025651
Abstract:Carbohydrates are generally considered to be poorly immunogenic. Therefore, new approaches for enhancing their immunogenicity are important for the development of carbohydrates as vaccine components. We hypothesized that conjugation of an l-rhamnose (Rha) moiety to a carbohydrate antigen would enhance the antigenicity of the antigen in mice possessing anti-Rha antibodies via an antibody-dependent antigen uptake mechanism. To explore this hypothesis, we synthesized a single-molecule three-component vaccine containing the GalNAc-O-Thr (Tn) tumor-specific antigen, a 20 amino acid helper T-cell epitope (YAF) derived from an outer-membrane protein of Neisseria meningitides, and a Rha moiety. The vaccine was synthesized by automated Fmoc-based solid-phase peptide synthesis and deacetylated by brief treatment with NaOMe. Groups of female BALB/c mice were immunized and boosted with Rha-ovalbumin (Rha-OVA) formulated with either TiterMax Gold or Sigma Adjuvant System for a period of 35 days in order to determine optimal conditions for generating anti-Rha titers in mice. Anti-Rha antibody titers were >100 fold higher in groups of mice immunized with Rha-OVA than in the control groups. Mice producing anti-Rha were challenged with Rha-YAF-Tn or YAF-Tn. Sera collected from the groups initially immunized with Rha-OVA and later challenged with Rha-YAF-Tn showed a 2-fold increase in anti-Tn titer at 1/100 serum dilution relative to mice not immunized with Rha-OVA. An in vitro T-cell proliferation study using cells primed with either Rha-YAF-Tn or YAF-Tn was done to examine possible differences in antigen uptake and presentation due to anti-Rha antibody and chemical modification. Proliferation of T cells was stimulated by a 10-fold lower antigen concentration in the presence of Rha antibodies. The results strongly suggest that T cells present in the spleen were presented with higher concentrations of Rha-YAF-Tn as a result of the presence of the anti-Rha antibodies.
Reference Type:Literature
PubMed ID:21080675
Journal:J Am Chem Soc
Journal Volume:132
Article Pages:17236-46
Journal ISSN:1520-5126
Article Chemical List:Antibodies;Antigens, Tumor-Associated, Carbohydrate;Epitopes;Serum Albumin, Bovine;Tn antigen;Toll-Like Receptors;Vaccines;Hemocyanin;keyhole-limpet hemocyanin;Rhamnose
Article MeSH List:Amino Acid Sequence; Animals; Antibodies(immunology); Antigens, Tumor-Associated, Carbohydrate(metabolism); Cell Proliferation; Chemistry Techniques, Synthetic; Epitopes(immunology); Female; Hemocyanin(metabolism); Mice; Molecular Sequence Data; Rhamnose(chemistry; immunology); Serum Albumin, Bovine(metabolism); T-Lymphocytes(cytology; immunology); Toll-Like Receptors(metabolism); Vaccines(chemical synthesis; chemistry; immunology; metabolism)
Curation Last Updated:2014-07-16 23:14:32