A Comparative Study of Different Presentation Strategies for an HIV Peptide Immunogen

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• 作者：Luis J. Cruz ; Enrique Iglesias ; Julio C. Aguilar ; Luis J. Gonzá ; lez ; Osvaldo Reyes ; Fernando Albericio ; and David Andreu
• 刊名：Bioconjugate Chemistry
• 出版年：2004
• 出版时间：January 2004
• 年：2004
• 卷：15
• 期：1
• 页码：112 - 120
• 全文大小：149K
• 年卷期：v.15,no.1(January 2004)
• ISSN：1520-4812

文摘

Different strategies have been used to increase the immunogenicity of an antigenic HIV peptide as avaccine candidate. The selected B-cell epitope comprises 15 amino acids (317-331) of the V3 regionof HIV-1, JY1 isolate (subtype D), in tandem with a T-helper epitope corresponding to the 830-844region of tetanus toxoid. Several presentations, including oligomerization, multiple antigenic peptidedendrimers, and conjugation to dextran beads or to other macromolecular carriers, have beensynthesized and evaluated. Murine sera from the different presentations of the V3 epitope have beencompared with regard to antibody titers and cross-reactivity with heterologous HIV subtypes. Thedendrimer version of the peptide conjugated to HBsAg protein was a better immunogen than thedendrimer alone and showed a higher immunogenicity than other multimeric presentations or thanthe peptide alone conjugated to dextran. The dendrimer version, either alone or conjugated to HBSAg,enhanced cross-reactivity toward heterologous V3 sequences relative to monomeric peptide. In addition,fine epitope mapping of the entire JY1 sequence by sera from the different immunization groups wasperformed by the spot synthesis technique. Results showed that the amino acids involved in molecularrecognition were LXQXXY or LXQXLY, with particularly strong recognition of the C-terminal regionLGQALY. However, cross-reactivity toward the heterologous sequences did not completely correlatewith recognition of particular amino acids in the primary sequences. These results can find applicationin the development of HIV vaccine candidates.