title: Isolation and characterization of a novel neutralizing antibody targeting the CD4-binding site of HIV-1 gp120.
abstract: Isolation and characterization of novel HIV-1 neutralizing antibodies assists the development of effective AIDS vaccines and immune therapeutics. In this study, we constructed a phage display antibody library by using the PBMC samples of a clade B' HIV-1-infected long-term nonprogressor (LTNP) whose sera exhibited broadly neutralizing activity. A novel human monoclonal antibody (hMAb), termed A16, was identified by panning the library with two clades of HIV-1 Env glycoproteins. We demonstrated that A16 neutralized 32% of 73 tested HIV-1 isolates and it targeted the CD4-binding site (CD4bs) of gp120 with high affinity. By selecting the peptide mimotopes in combination with computational algorithms and site-directed mutagenesis, the epitope of A16 was mapped to the structurally conserved sites located within the β1-α1, loop D, β20-β21 (bridging sheet) and β24-α5 of gp120, which critically determine the CD4 binding and are involved in the epitopes of CD4bs-directed antibodies. Our studies have shed new insights for the immune response of HIV-1 infection and offered a new tool for designing vaccine immunogens and antibody-based immune therapy.
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Man
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zonglin
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Yang
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Youxiang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: yhe@ipb.pumc.edu.cn.
authors.forename: Yuxian
authors.initials: Y
authors.lastname: He
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000378:metabolism; D000915:Antibody Affinity / Q000276:immunology; D001666:Binding Sites, Antibody / Q000235:genetics; D015704:CD4 Antigens / Q000378:metabolism*; D002460:Cell Line; D003429:Cross Reactions / Q000276:immunology; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000276:immunology* / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D008958:Models, Molecular; D009500:Neutralization Tests; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007140:Immunoglobulin Fab Fragments
keywords: Epitope; HIV-1; Neutralizing antibody; Vaccine