Identification of a novel CD4i human monoclonal antibody Fab that neutralizes HIV-1 primary isolates from different clades.
A new human monoclonal antibody (hmAb), designated m16, was selected by sequential antigen panning (SAP) of a human phage display library against recombinant soluble HIV-1 envelope glycoproteins (Envs) (gp140s) and their complexes with soluble CD4. It bound with high (nM) affinity to gp120 and gp140; the binding was further enhanced by interactions of the Envs with CD4. m16 inhibited cell fusion mediated by the Envs of 9 HIV-1 isolates from clades A, B, E and G with potency on average comparable to that of the broadly neutralizing human monoclonal antibody Fab X5. The identification of a new hmAb with broad neutralizing activity that exhibits differential inhibitory profile suggests a potential for its use as a component of anti-HIV-1 treatments.
Zhang
Mei-Yun
MY
Human Immunovirology and Computational Biology Group, LECB, CCR, NCI-Frederick, NIH, Frederick, MD 21702, USA.
Shu
Yuuei
Y
Sidorov
Igor
I
Dimitrov
Dimiter S
DS
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D015704:CD4 Antigens / Q000276:immunology; D002459:Cell Fusion; D015686:Gene Products, env / Q000276:immunology; D005838:Genotype; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D009500:Neutralization Tests; D019151:Peptide Library; D011485:Protein Binding; D011994:Recombinant Proteins / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015686:Gene Products, env; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D007140:Immunoglobulin Fab Fragments; D019151:Peptide Library; D011994:Recombinant Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1