title: Anti-idiotype monoclonal antibody elicits broadly neutralizing anti-gp120 antibodies in monkeys.
abstract: Murine monoclonal antibodies (mAbs) were raised against human, polyclonal, anti-gp120 antibodies (Ab1) and were selected for binding to broadly neutralizing anti-gp120 antibodies in sera positive for human immunodeficiency virus (HIV). One anti-idiotype mAb (Ab2), 3C9, was found to be specific for human anti-gp120 antibodies directed against an epitope around the conserved CD4 attachment site of gp120. The 3C9 reactive human anti-gp120 antibodies (3C9+ Ab) neutralized MN, IIIB, RF, and four primary isolates of HIV type 1 (HIV-1). Cynomolgus monkeys were immunized with 3C9 in adjuvant to test whether this anti-idiotype mAb could induce neutralizing anti-gp120 antibodies. The results show that purified anti-anti-idiotype antibodies (Ab3) from 3C9 immune sera bind to an epitope around the CD4 attachment site of gp120SF and gp120IIIB. Furthermore, purified gp120-specific Ab3 neutralize MN, IIIB, and RF isolates. These results demonstrate that primates immunized with an anti-idiotype mAb produce broadly neutralizing anti-HIV-1 antibodies. Since this anti-idiotype mAb was selected by identifying a clonotypic marker, its biological activity can be explained as the results of clonotypic B-cell stimulation.
authors.affiliation: IDEC Pharmaceuticals Corporation, La Jolla, CA 92037.
authors.forename: C Y
authors.initials: CY
authors.lastname: Kang
authors.forename: P
authors.initials: P
authors.lastname: Nara
authors.forename: S
authors.initials: S
authors.lastname: Chamat
authors.forename: V
authors.initials: V
authors.lastname: Caralli
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.forename: M L
authors.initials: ML
authors.lastname: Nguyen
authors.forename: H
authors.initials: H
authors.lastname: Yoshiyama
authors.forename: W J
authors.initials: WJ
authors.lastname: Morrow
authors.forename: D D
authors.initials: DD
authors.lastname: Ho
authors.forename: H
authors.initials: H
authors.lastname: Köhler
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008252:Macaca fascicularis; D009500:Neutralization Tests
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120