Peptides selected from a phage display library with an HIV-neutralizing antibody elicit antibodies to HIV gp120 in rabbits, but not to the same epitope.
Monoclonal antibodies specific for the conserved CD4 binding site region of the HIV envelope protein gp120 were used to select phage from two different random peptide display libraries. Synthetic peptides were made with sequences corresponding to those displayed on the selected phage, and peptide-protein fusions were expressed that contained the selected phage-displayed peptide sequence and either the N-terminal domain of the phage pIII protein or the small heat shock protein of Methanococcus jannaschii or both. For monoclonal antibody 5145A, these constructs containing the selected peptide sequences were all capable of specifically inhibiting the binding of 5145A to HIV-1 gp120. Rabbits immunized with peptide-protein fusions produced antisera that bound to recombinant HIV-1 gp120, but did not bind to HIV-infected cells nor neutralize HIV. The antisera also did not compete with CD4 or antibodies to the CD4 binding site for binding to gp120.
Wilkinson
Royce A
RA
Departments of Chemistry, Montana State University, Bozeman, Montana 59717-3400, USA.
Evans
Jody R
JR
Jacobs
Jon M
JM
Slunaker
Dustin
D
Pincus
Seth H
SH
Pinter
Abraham
A
Parkos
Charles A
CA
Burritt
James B
JB
Teintze
Martin
M
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000914:Antibodies, Viral / Q000378:metabolism; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D009500:Neutralization Tests; D019151:Peptide Library; D010455:Peptides / Q000276:immunology* / Q000302:isolation & purification; D011485:Protein Binding; D011817:Rabbits
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D019151:Peptide Library; D010455:Peptides