title: Synergistic neutralization of human immunodeficiency virus type 1 by combinations of human monoclonal antibodies.
abstract: The ability of antibodies to the V3 region and the CD4-binding domain (CD4bd) of human immunodeficiency virus type 1 (HIV-1) to act in synergy to neutralize HIV has been demonstrated previously. However, synergy between antibodies to other HIV-1 epitopes has not been studied. We have used 21 combinations of human monoclonal antibodies (MAbs) directed against different epitopes of the gp120 and gp41 proteins of HIV-1 to evaluate their ability to act in synergy to neutralize HIV-1. Combinations of anti-V3 and anti-CD4bd antibodies, anti-V3 and anti-gp120 C-terminus antibodies, anti-CD4bd and anti-C-terminus antibodies, anti-V3 and anti-gp41 antibodies, and anti-CD4bd and anti-gp41 antibodies were tested. Our results show that some, but not all anti-V3 antibodies can act in synergy with anti-CD4bd antibodies. In addition, for the first time, antibodies to the C-terminus region have been found to act in synergy with the anti-CD4bd antibodies. Various anti-CD4bd MAbs also act in synergy when used together. The use of such cocktails of human MAbs for passive immunization against HIV-1 may prove to be important for therapy in postexposure settings and for prevention of maternal-fetal transmission of the virus. The results also provide information on the types of antibodies that should be elicited by an effective vaccine.
authors.affiliation: Veterans Administration Medical Center, New York, New York 10010.
authors.forename: S
authors.initials: S
authors.lastname: Laal
authors.forename: S
authors.initials: S
authors.lastname: Burda
authors.forename: M K
authors.initials: MK
authors.lastname: Gorny
authors.forename: S
authors.initials: S
authors.lastname: Karwowska
authors.forename: A
authors.initials: A
authors.lastname: Buchbinder
authors.forename: S
authors.initials: S
authors.lastname: Zolla-Pazner
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments