Increase in the immunogenicity of HIV peptide antigens by chemical linkage to polytuftsin (TKPR40).
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.
Gokulan
K
K
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi. gokulan@abgen.cvm.tamu.edu
Khare
S
S
Rao
D N
DN
D016915:AIDS Vaccines / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D019281:Dimerization; D004337:Drug Carriers / Q000138:chemical synthesis / Q000378:metabolism; D006678:HIV / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000276:immunology; D015488:HIV Antigens / Q000276:immunology* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000276:immunology / Q000378:metabolism; D006239:Haplotypes / Q000276:immunology; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis; D011108:Polymers / Q000138:chemical synthesis / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014405:Tuftsin / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism*
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D016207:Cytokines; D004337:Drug Carriers; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D010446:Peptide Fragments; D011108:Polymers; C053968:polytuftsin; D014405:Tuftsin