MIMOTOPE CONVERSION OF HIV-1 CARBOHYDRATE ANTIGENS

University Of Pennsylvania, Philadelphia PA

Investigators

Linked publications & trials

Abstract

DESCRIPTION: (Adapted from Applicant's Abstract) Carbohydrate antigens have been the basis for eliciting protective immune responses against many pathogens, yet this approach has not been adequately assessed in HIV research. Targeting carbohydrates could present new possibilities for group specific vaccine development because they are present on all isolates. Furthermore, anti-carbohydrate antibodies may sensitize HIV infected cells for complement-mediated cytolysis by targeting cell surface expressed glycoprotein. We have developed a program concerned with the interconversion of carbohydrate epitopes associated with HIV into a peptide-based vaccine strategy to augment carbohydrate cross-reactive systemic and mucosal responses. We have shown that peptides can induce carbohydrate cross-reactive IgM and IgG responses that can be further manipulated to participate in lysing HIV infected cells or target HIV virions. This proposal has three specific aims: 1) To further refine peptide mimotopes of HIV associated carbohydrate antigens. We evaluate the antigenic mimicry of peptide mimotopes by kinetic and binding parameters of peptides that compete with HIV associated carbohydrates for Con A and anti- carbohydrate antibody using BIACORE and ELISA analysis. 2) To evaluate mechanisms to enhance or augment immune responses to HIV-1 associated carbohydrates. Serological comparisons are made between peptide, carbohydrate conjugates and mimotope encoded DNA immunizations. 3.) To determine the extent to which priming and boosting strategies lead to enhanced carbohydrate cross-reactive systemic and mucosal anti-HIV antibody responses. Focus is placed on the ability to prime for an antibody response to envelope expressed carbohydrate and to have this response boosted with later injections of HIV-1 protein, carbohydrate-conjugates or carbohydrate expressing cells. Based upon preliminary evidence it is hypothesized that boosting will further augment or enhance carbohydrate cross-reactive IgG2a, IgA, and secretory IgM responses. Incorporation of encoded peptide mimotopes with HIV CTL epitopes into a DNA vaccine strategy further ensures HIV memory responses and augmented T cell immunity that can target infected cells. This is a unique approach using both antibodies and T cells to target infected cells. This approach could set the groundwork for further development, providing a novel strategy to supplement HIV vaccine research.