Design and synthesis of a self-assembling peptide derived from the envelope proteins of HIV type 1. An approach to heterovalent immunogens.
A chimeric peptide that included sequences from gp120 and gp41 of HIV type 1 was synthesized. Cleavage from solid support yielded a composite of self-oligomerized products with molecular masses ranging from 5 to about 9 kDa. The oligomer but not its reduced, monomeric form was recognized by human anti-HIV sera and at least one of the two lysines in the sequence was involved in antibody binding. The oligomeric peptide was immunogenic, yielding a conformation-specific antibody response. Co-oligomerization of a hepatitis B surface Ag-derived peptide and the HIV type 1-derived peptide yielded a bivalent product in which conformational integrity of the individual components was maintained. Immunization with this hybrid peptide resulted in conformation-specific antibodies to both epitopes in all four murine strains tested. Lymphocyte proliferation assays revealed that the T epitopes resident in both peptide sequences remained active in the hybrid peptide. These results demonstrate the potential of this approach in generating multi- and heterovalent immunogens which may eventually find application as vaccines.
Tripathy
S P
SP
AIDS Unit, National Institute of Virology, Pune, India.
Kumar
A
A
Manivel
V
V
Panda
S K
SK
Rao
K V
KV
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015195:Drug Design; D015483:HIV Antibodies / Q000096:biosynthesis; D015488:HIV Antigens / Q000737:chemistry*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011487:Protein Conformation; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D006514:Hepatitis B Surface Antigens; D010455:Peptides; D014614:Vaccines, Synthetic