AUGMENTING IMMUNE RESPONSES TO WEAK IMMUNOGENS

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The recent revolution in vaccine development has renewed the need for simple and general methods to increase antibody responses to weak immunogens. Accordingly, the present research is aimed at development of such a method to optimize antibody responses to antigenic peptides. The long term goal of the proposed research is to achieve a completely synthetic immunogen comprised of an adjuvant moiety, a carrier determinant that only stimulates T cells, and an antigenic peptide against which antibody will be made. Development of this system will circumvent several of the problems inherent in the traditional peptide-vaccine method where the antigenic peptide is conjugated to a protein carrier. The research will proceed in two stages. The first stage will focus on the antigenic peptide-carrier conjugate. A small (m.w. = 409) synthetic carrier determinant, L- Tyrosine-P-azobenzenearsonate (ABA-Try) will be evaluated in three anti-peptide response system (one poliovirus VPI peptide, and two HIV env peptides). Special emphasis will be placed on elucidation of antigen-structural variables as they affect immunogenicity. In particular the spacing and orientation of the antigentic peptide relative to the carrier determinant ABA-Tyr will be investigated. The second stage will build upon the first by investigating the attachment of a synthetic adjuvant moiety to each of the optimal conjugates. Emphasis in this stage will be placed on the nature of the moiety and its spacing and orientation relative to the antigenic peptide and carrier determinant. Because the second phase is entirely dependent upon success in the first phase, funding is initially requested only for the first phase which can be completed in 3 years.