title: Cross-clade neutralizing activity of human anti-V3 monoclonal antibodies derived from the cells of individuals infected with non-B clades of human immunodeficiency virus type 1.
abstract: The majority of global human immunodeficiency virus infections are caused by viruses characterized by a GPGQ motif at the tip of the V3 loop. Characterization of anti-V3 monoclonal antibodies (MAbs) that neutralize isolates with the GPGQ V3 motif is an important step in designing vaccines that will induce such Abs. Consequently, seven human anti-V3 MAbs derived from the cells of individuals infected with non-B-subtype viruses (anti-V3(non-B) MAbs) were generated from the cells of individuals from Africa infected with circulating recombinant forms CRF02_AG, CRF09_cpx, and CRF13_cpx, each of which contains a subtype A env gene. Sequence analysis of plasma viruses revealed a GPGQ motif at the apex of the V3 loop from six of the seven subjects and a GPGR motif from one subject. The MAbs were selected with fusion proteins (FP) containing V3(92UG037.8) or V3(JR-CSF) from subtype A or B, respectively. In virus binding assays, five of the seven (71%) anti-V3(non-B) MAbs bound to V3-FPs from both subtype A and subtype B, while only four of the nine (44%) anti-V3(B) MAbs recognized both V3-FPs. Using two neutralization assays, both the anti-V3(non-B) and the anti-V3(B) MAbs neutralized subtype B viruses with similar activities, while the anti-V3(non-B) MAbs exhibited a tendency toward both increased potency and breadth of neutralization against non-B viruses compared to anti-V3(B) MAbs. Statistical significance was not achieved, due in large measure to the sizes of the MAb panels, but the overall pattern of data strongly suggests that viruses with the GPGQ motif at the tip of the V3 loop induce anti-V3 Abs with broader cross-neutralizing activity than do viruses with the GPGR motif.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Miroslaw K
authors.initials: MK
authors.lastname: Gorny
authors.forename: Constance
authors.initials: C
authors.lastname: Williams
authors.forename: Barbara
authors.initials: B
authors.lastname: Volsky
authors.forename: Kathy
authors.initials: K
authors.lastname: Revesz
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wang
authors.forename: Sherri
authors.initials: S
authors.lastname: Burda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimura
authors.forename: Frank A J
authors.initials: FA
authors.lastname: Konings
authors.forename: Arthur
authors.initials: A
authors.lastname: Nádas
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Anyangwe
authors.forename: Phillipe
authors.initials: P
authors.lastname: Nyambi
authors.forename: Chavdar
authors.initials: C
authors.lastname: Krachmarov
authors.forename: Abraham
authors.initials: A
authors.lastname: Pinter
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
mesh_terms: D020816:Amino Acid Motifs / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013045:Species Specificity; D014779:Virus Replication / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015686:Gene Products, env; D015483:HIV Antibodies; D011993:Recombinant Fusion Proteins