title: Broadly cross-reactive HIV neutralizing human monoclonal antibody Fab selected by sequential antigen panning of a phage display library.
abstract: Identification of broadly cross-reactive human monoclonal antibodies (mAbs) has major implications for development of vaccines, inhibitors and research tools. Here we describe a sequential antigen panning (SAP) methodology that may facilitate the selection of such antibodies. An HIV-specific antibody Fab (m18) was selected from a human Fab phage-display library by SAP against several recombinant soluble HIV envelope glycoproteins (Envs) and Env-sCD4 complexes. This Fab bound to a variety of recombinant soluble Envs (gp140s) from primary HIV isolates representing different clades, and inhibited cell fusion and virus entry mediated by Envs of primary HIV isolates. The methodology and the results may have implications for development of HIV vaccines and inhibitors, as well as for identification of antibodies to conserved epitopes on rapidly mutating viruses and cells.
authors.affiliation: Laboratory of Experimental and Computational Biology, CCR, NCI-Frederick, NIH, Bldg 469, Rm 246, P.O. Box B, Miller Drive, Frederick, MD 21702-1201, USA.
authors.forename: Mei-Yun
authors.initials: MY
authors.lastname: Zhang
authors.forename: Yuuei
authors.initials: Y
authors.lastname: Shu
authors.forename: Sanjay
authors.initials: S
authors.lastname: Phogat
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xiao
authors.forename: Fatim
authors.initials: F
authors.lastname: Cham
authors.forename: Peter
authors.initials: P
authors.lastname: Bouma
authors.forename: Anil
authors.initials: A
authors.lastname: Choudhary
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Feng
authors.forename: Inaki
authors.initials: I
authors.lastname: Sanz
authors.forename: Susanna
authors.initials: S
authors.lastname: Rybak
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Broder
authors.forename: Gerald V
authors.initials: GV
authors.lastname: Quinnan
authors.forename: Thomas
authors.initials: T
authors.lastname: Evans
authors.forename: Dimiter S
authors.initials: DS
authors.lastname: Dimitrov
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D003429:Cross Reactions; D015686:Gene Products, env / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D008561:Membrane Fusion; D019151:Peptide Library; D054299:env Gene Products, Human Immunodeficiency Virus
chemical_list: D000911:Antibodies, Monoclonal; D015686:Gene Products, env; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007140:Immunoglobulin Fab Fragments; D019151:Peptide Library; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1