Synthetic peptides from a conserved region of gp120 induce broadly reactive anti-HIV responses.
In our efforts to identify products that might be used for active immunotherapy in human immunodeficiency virus (HIV) infection, we have studied synthetic peptides derived from the CD4 attachment site of gp120. Two peptides have emerged with particularly interesting properties. The first (B138) is linear and spans the envelope residues 421-438; the second (1005/45) encompasses amino acids 418-445 and is cyclized by way of a disulphide bond joining its terminal cysteines. Both species have been shown to inhibit syncytial formation in a conventional bioassay, B138 being the most efficient. Both peptides elicit high titres of anti-peptide antibodies in immunized mice, rabbits and goats, with titres exceeding 1:10(5) in many cases. A substantial portion of this response is directed against gp120 as determined by enzyme-linked immunosorbent assay (ELISA). Analysis by flow cytometry has demonstrated that the antisera are broadly reactive with multiple diverse strains of HIV. The anti-gp120 activity of the anti-peptide antiserum was further confirmed by radioimmuno-precipitation (RIP) assays. Furthermore, RIP analysis and inhibition experiments in a GD4-gp120 binding assay have revealed that anti-peptide sera contain antibodies directed against the CD4 attachment site on gp120 and interfere with this receptor-ligand interaction.
Morrow
W J
WJ
IDEC Pharmaceuticals Corporation, La Jolla, California 92037.
Williams
W M
WM
Whalley
A S
AS
Ryskamp
T
T
Newman
R
R
Kang
C Y
CY
Chamat
S
S
Köhler
H
H
Kieber-Emmons
T
T
D000818:Animals; D001667:Binding, Competitive / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002460:Cell Line; D006041:Goats; D015483:HIV Antibodies / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000138:chemical synthesis; D011817:Rabbits; D015531:Radioimmunoprecipitation Assay; D014614:Vaccines, Synthetic / Q000276:immunology*
D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; D014614:Vaccines, Synthetic