AEGiS-11IAC: Inactivation of HIV-1 by recombinant antibodies.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

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Inactivation of HIV-1 by recombinant antibodies.

Int Conf AIDS 1996 Jul 7-12; 11:9 (abstract no. Mo.A.274)
Parren PW, Fisicaro P, Barbas CF 3d, Burton DR; The Scripps Research Institute, Dept of Immunology and Molecular Biology, La Jolla, CA, USA. Fax: (619) 554-6360. E-mail: parren@scripps.edu.

OBJECTIVE: To isolate broadly neutralizing recombinant antibodies to HIV-1 and characterize neutralization in vitro and in vivo.

METHODS: Antibody phage display libraries were prepared from long-term HIV-1 seropositve donors. In initial experiments, monomeric HIV-1 envelope subunits were used for enrichment and screening of clones. Selection for potency and strain cross-reactivity was achieved through experimental design. In more recent experiments we selected libraries on oligomeric mature HIV-1 envelope by panning directly on infected cells or antibody-captured virus. The most potent neutralizing antibody was evaluated for in vivo efficacy in SCID mice reconstituted with human PBLs.

RESULTS: Large numbers of recombinant human antibodies reactive with many different epitopes on the envelope of HIV-1 have been generated from phage-display libraries. A broadly reactive anti-gp120 (CD4 binding site) antibody, termed IGG1 b12, which neutralizes a wide range of primary isolates of HIV-1 (clades A through F) at biologically relevant concentrations was identified. This demonstrates that broad neutralization of HIV-1 primary isolates is possible with a single antibody. This antibody can completely protect hu-PBL-SCID mice from HIV-1 infection. We have some indications as to the origins of the potency. Evidence from antibody binding to infected cells suggests that IGG1 b12 recognizes a native (oligomeric) conformation of gp120 more effectively than other antibodies directed against the CD4 binding site. Identification of the exact b12-epitope has important implications for vaccine design.

CONCLUSIONS: A potent broadly neutralizing human antibody against HIV-1 has been identified. We demonstrate for the first time that complete protection against HIV-1 infection can be achieved in the hu-PBL-SCID model by passive immunization with physiologically relevant doses of a human monoclonal antibody. This antibody is being developed for immunoprophylaxis and immunotherapy of HIV-1 infection in humans.

Keywords: AEGIS, HIV-1, Antigens, CD4, HIV Infections, Antibodies, Monoclonal, Mice, SCID, Epitopes, Immunization, Passive, Immunoglobulin G, Binding Sites, Mice, Animal, Human, In Vitro, ICA11KWDaegis,hiv-1,antigens,cd4,hivinfections,antibodies,monoclonal,mice,scid,epitopes,immunization,passive,immunoglobuling,bindingsites,mice,animal,human,invitro,ica11

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MoA274

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