Increase in the immunogenicity of HIV peptide antigens by chemical linkage to polytuftsin (TKPR40).

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Increase in the immunogenicity of HIV peptide antigens by chemical linkage to polytuftsin (TKPR40).

DNA Cell Biol. 1999 Aug;18(8):623-30. Unique Identifier : AIDSLINE MED/99392354
Gokulan K; Khare S; Rao DN; Department of Biochemistry, All India Institute of Medical; Sciences, New Delhi. gokulan@abgen.cvm.tamu.edu

Abstract: The use of synthetic peptide antigens in human prophylaxis still suffers from the very important problem of finding suitable carriers devoid of side effects. A desirable carrier for use in humans would be poorly immunogenic by itself, yet it would enhance the immune response to the peptide antigen. In the study reported herein, we examined the role of polytuftsin (TKPR40), a synthetic polymer of the natural immunomodulator tuftsin, as a carrier for synthetic peptides of HIV derived from the gp41 and gp120 proteins. Chimeric immunogens were constructed by chemical linkage between synthetic peptides of HIV and polytuftsin. These were employed for immunization of mice of different MHC haplotypes, and the humoral and cellular immune responses developed against the peptides were assessed by measuring total IgG, IgG, subclasses, T-cell proliferation, and in vitro cytokine release. A significantly stronger immune response was observed in mice immunized with the peptide-polytuftsin conjugates than in mice receiving the peptide dimers (peptide-peptide). Peptide-polytuftsin conjugates induced IgG2a and IgG2b isotype switching after both primary and secondary immunization. In addition, there was a positive correlation between the amounts of cytokines and the shift in the IgG isotypes. These data suggest that the use of polytuftsin as a carrier may increase the immune response against poorly immunogenic synthetic peptides.

Keywords: JOURNAL ARTICLE AIDS Vaccines/CHEMICAL SYNTHESIS/IMMUNOLOGY/METABOLISM Adjuvants, Immunologic/CHEMICAL SYNTHESIS/*METABOLISM Animal Cells, Cultured Cytokines/BIOSYNTHESIS/IMMUNOLOGY Dimerization Drug Carriers/CHEMICAL SYNTHESIS/METABOLISM HIV/*IMMUNOLOGY HIV Antibodies/*BIOSYNTHESIS/IMMUNOLOGY HIV Antigens/*IMMUNOLOGY/METABOLISM HIV Envelope Protein gp120/IMMUNOLOGY/METABOLISM HIV Envelope Protein gp41/IMMUNOLOGY/METABOLISM Haplotypes/IMMUNOLOGY IgG/BIOSYNTHESIS/IMMUNOLOGY Immunoglobulin Class Switching Lymphocyte Transformation/IMMUNOLOGY Macrophages/IMMUNOLOGY Major Histocompatibility Complex/IMMUNOLOGY Mice Mice, Inbred Strains Peptide Fragments/CHEMICAL SYNTHESIS/*IMMUNOLOGY/METABOLISM Phagocytosis Polymers/CHEMICAL SYNTHESIS/*METABOLISM Support, Non-U.S. Gov't T-Lymphocytes/IMMUNOLOGY Tuftsin/CHEMICAL SYNTHESIS/IMMUNOLOGY/*METABOLISM
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A99B1134

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