Isolation and characterization of a novel neutralizing antibody targeting the CD4-binding site of HIV-1 gp120
| Autor: | Lingli Yang, Youxiang Sun, Zonglin Qiu, Yuxian He, Lai Man, Yuanyuan Qiao |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine Phage display CD4 antigen Protein Conformation medicine.drug_class 030106 microbiology Antibody Affinity HIV Infections Cross Reactions HIV Antibodies HIV Envelope Protein gp120 Monoclonal antibody Epitope Cell Line Epitopes Immunoglobulin Fab Fragments 03 medical and health sciences chemistry.chemical_compound Neutralization Tests Virology medicine Humans Amino Acid Sequence Binding site Neutralizing antibody AIDS Vaccines Pharmacology biology Antibodies Monoclonal Antibodies Neutralizing 030104 developmental biology Epitope mapping chemistry CD4 Antigens HIV-1 biology.protein Binding Sites Antibody Antibody Epitope Mapping Protein Binding |
| Zdroj: | Antiviral Research. 132:252-261 |
| ISSN: | 0166-3542 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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