Polyepitope DNA Immunization: Induction of Carbohydrate Cross-reactive Antibody Response with HIV gp120 Specific Cellular Responses

Thomas Kieber-Emmons

《Journal of Genetics and Molecular Biology》 13卷1期 (2002/03) Pp. 58-58

https://doi.org/10.30047/JGMB.200203.0015

並列摘要

Protective immunity to many pathogens is based upon eliciting an immune response to carbohydrate antigens. The HIV envelop glycoprotein is highly glycosylated and thus, HIV-1 associated carbohydrate antigens are potential vaccine targets. However, the development of carbohydrate-based vaccines is severely limited by our inability to synthesize these complex structures in vitro. To elicit carbohydrate-directed immune responses, we have initiated a research program based on the ability of peptides to mimic carbohydrate epitopes. Targeting carbohydrates on the surface of envelope glycoprotein gpl20 could present new possibilities for group-specific vaccine development because they are present on all isolates. Using systematic approaches involving molecular modeling and phage display libraries, we are developing prototypic peptide mimeotope templates of HIV-1-associated carbohydrate antigens. We have shown that immunization with peptide mimeotopes of nominal HIV-1 associated carbohydrate antigens elicit cross-reactive antibody responses to HIV-1. In an attempt to further set strategies for the design and development of effective anti-carbohydrate vaccines, we converted the mineotopes to DNA sequences, immunized mice with generated plasmids and confirmed the induction of cross-reactive carbohydrate IgG with a predominance of IgG2a. DNA immunization with encoded mimeotopes primed for a booster reponse upon challenge with synthetic carbohydrate. The IgG component of the generated serum was reactive with glycosylated gpl20. The inclusion of a CTL epitope from the HIV-1 envelope protein in the expression cassette, and co-administration with IL-12 or GMCSF encoding plasmids, induced cellular responses to HIV-1 envelope. These results indicate the feasibility of combining an HIV-1 specific cellular response with a carbohydrate cross-reactive humoral response against gpl20 and that cytokine gene co-injection with the antigenic DNA selectively improves the immune response. These results define a novel strategy for future HIV vaccine development.