title: Anti-V3 monoclonal antibodies display broad neutralizing activities against multiple HIV-1 subtypes.
abstract: BACKGROUND
  The V3 loop of the HIV-1 envelope (Env) glycoprotein gp120 was identified as the "principal neutralizing domain" of HIV-1, but has been considered too variable to serve as a neutralizing antibody (Ab) target. Structural and immunochemical data suggest, however, that V3 contains conserved elements which explain its role in binding to virus co-receptors despite its sequence variability. Despite this evidence of V3 conservation, the ability of anti-V3 Abs to neutralize a significant proportion of HIV-1 isolates from different subtypes (clades) has remained controversial.
  
  
  METHODS
  HIV-1 neutralization experiments were conducted in two independent laboratories to test human anti-V3 monoclonal Abs (mAbs) against pseudoviruses (psVs) expressing Envs of diverse HIV-1 subtypes from subjects with acute and chronic infections. Neutralization was defined by 50% inhibitory concentrations (IC(50)), and was statistically assessed based on the area under the neutralization titration curves (AUC).
  
  
  RESULTS
  Using AUC analyses, statistically significant neutralization was observed by >or=1 anti-V3 mAbs against 56/98 (57%) psVs expressing Envs of diverse subtypes, including subtypes A, AG, B, C and D. Even when the 10 Tier 1 psVs tested were excluded from the analysis, significant neutralization was detected by >or=1 anti-V3 mAbs against 46/88 (52%) psVs from diverse HIV-1 subtypes. Furthermore, 9/24 (37.5%) Tier 2 viruses from the clade B and C standard reference panels were neutralized by >or=1 anti-V3 mAbs. Each anti-V3 mAb tested was able to neutralize 28-42% of the psVs tested. By IC(50) criteria, 40/98 (41%) psVs were neutralized by >or=1 anti-V3 mAbs.
  
  
  CONCLUSIONS
  Using standard and new statistical methods of data analysis, 6/7 anti-V3 human mAbs displayed cross-clade neutralizing activity and revealed that a significant proportion of viruses can be neutralized by anti-V3 Abs. The new statistical method for analysis of neutralization data provides many advantages to previously used analyses.
authors.affiliation: Department of Pathology, New York University Langone School of Medicine, New York, New York, United States of America. catarina.hioe@nyumc.org
authors.forename: Catarina E
authors.initials: CE
authors.lastname: Hioe
authors.forename: Terri
authors.initials: T
authors.lastname: Wrin
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yu
authors.forename: Blake
authors.initials: B
authors.lastname: Wood
authors.forename: Steve
authors.initials: S
authors.lastname: Self
authors.forename: Constance
authors.initials: C
authors.lastname: Williams
authors.forename: Miroslaw K
authors.initials: MK
authors.lastname: Gorny
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019540:Area Under Curve; D017124:Conserved Sequence / Q000276:immunology; D003429:Cross Reactions / Q000276:immunology*; D003627:Data Interpretation, Statistical; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology*; D015728:Receptors, HIV
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D015728:Receptors, HIV