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Identification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody.

Publication ,  Journal Article
Zhang, M-Y; Xiao, X; Sidorov, IA; Choudhry, V; Cham, F; Zhang, PF; Bouma, P; Zwick, M; Choudhary, A; Montefiori, DC; Broder, CC; Burton, DR ...
Published in: J Virol
September 2004

The identification and characterization of new human monoclonal antibodies (hMAbs) able to neutralize primary human immunodeficiency virus type 1 (HIV-1) isolates from different subtypes may help in our understanding of the mechanisms of virus entry and neutralization and in the development of entry inhibitors and vaccines. For enhanced selection of broadly cross-reactive antibodies, soluble HIV-1 envelope glycoproteins (Envs proteins) from two isolates complexed with two-domain soluble CD4 (sCD4) were alternated during panning of a phage-displayed human antibody library; these two Env proteins (89.6 and IIIB gp140s), and one additional Env (JR-FL gp120) alone and complexed with sCD4 were used for screening. An antibody with relatively long HCDR3 (17 residues), designated m14, was identified that bound to all antigens and neutralized heterologous HIV-1 isolates in multiple assay formats. Fab m14 potently neutralized selected well-characterized subtype B isolates, including JRCSF, 89.6, IIIB, and Yu2. Immunoglobulin G1 (IgG1) m14 was more potent than Fab m14 and neutralized 7 of 10 other clade B isolates; notably, although the potency was on average significantly lower than that of IgG1 b12, IgG1 m14 neutralized two of the isolates with significantly lower 50% inhibitory concentrations than did IgG1 b12. IgG1 m14 neutralized four of four selected clade C isolates with potency higher than that of IgG1 b12. It also neutralized 7 of 17 clade C isolates from southern Africa that were difficult to neutralize with other hMAbs and sCD4. IgG1 m14 neutralized four of seven primary HIV-1 isolates from other clades (A, D, E, and F) much more efficiently than did IgG1 b12; for the other three isolates, IgG b12 was much more potent. Fab m14 bound with high (nanomolar range) affinity to gp120 and gp140 from various isolates; its binding was reduced by soluble CD4 and antibodies recognizing the CD4 binding site (CD4bs) on gp120, and its footprint as defined by alanine-scanning mutagenesis overlaps that of b12. These results suggest that m14 is a novel CD4bs cross-reactive HIV-1-neutralizing antibody that exhibits a different inhibitory profile compared to the only known potent broadly neutralizing CD4bs human antibody, b12, and may have implications for our understanding of the mechanisms of immune evasion and for the development of inhibitors and vaccines.

Duke Scholars

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Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

September 2004

Volume

78

Issue

17

Start / End Page

9233 / 9242

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Peptide Library
  • Neutralization Tests
  • Mutagenesis
  • Molecular Sequence Data
  • Kinetics
  • Immunoglobulin G
  • Immunoglobulin Fab Fragments
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Zhang, M.-Y., Xiao, X., Sidorov, I. A., Choudhry, V., Cham, F., Zhang, P. F., … Dimitrov, D. S. (2004). Identification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody. J Virol, 78(17), 9233–9242. https://doi.org/10.1128/JVI.78.17.9233-9242.2004
Zhang, Mei-Yun, Xiaodong Xiao, Igor A. Sidorov, Vidita Choudhry, Fatim Cham, Peng Fei Zhang, Peter Bouma, et al. “Identification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody.J Virol 78, no. 17 (September 2004): 9233–42. https://doi.org/10.1128/JVI.78.17.9233-9242.2004.
Zhang M-Y, Xiao X, Sidorov IA, Choudhry V, Cham F, Zhang PF, et al. Identification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody. J Virol. 2004 Sep;78(17):9233–42.
Zhang, Mei-Yun, et al. “Identification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody.J Virol, vol. 78, no. 17, Sept. 2004, pp. 9233–42. Pubmed, doi:10.1128/JVI.78.17.9233-9242.2004.
Zhang M-Y, Xiao X, Sidorov IA, Choudhry V, Cham F, Zhang PF, Bouma P, Zwick M, Choudhary A, Montefiori DC, Broder CC, Burton DR, Quinnan GV, Dimitrov DS. Identification and characterization of a new cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody. J Virol. 2004 Sep;78(17):9233–9242.

Published In

J Virol

DOI

ISSN

0022-538X

Publication Date

September 2004

Volume

78

Issue

17

Start / End Page

9233 / 9242

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Peptide Library
  • Neutralization Tests
  • Mutagenesis
  • Molecular Sequence Data
  • Kinetics
  • Immunoglobulin G
  • Immunoglobulin Fab Fragments
  • Humans