Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters











Database
Language
Publication year range
1.
Sci China Life Sci ; 66(4): 729-742, 2023 04.
Article in English | MEDLINE | ID: mdl-36853487

ABSTRACT

Respiratory syncytial virus (RSV) continues to pose serious threats to pediatric populations due to the lack of a vaccine and effective antiviral drugs. RSV fusion (F) glycoprotein mediates viral-host membrane fusion and is a key target for neutralizing antibodies. We generated 23 full-human monoclonal antibodies (hmAbs) against prefusion F protein (pre-F) from a healthy adult with natural RSV infection by single B cell cloning technique. A highly potent RSV-neutralizing hmAb, named as 25-20, is selected, which targets a new site Ø-specific epitope. Site-directed mutagenesis and structural modelling analysis demonstrated that 25-20 mainly targets a highly conserved hydrophobic region located at the a4 helix and a1 helix of pre-F, indicating a site of vulnerability for drug and vaccine design. It is worth noting that 25-20 uses an unreported inferred germline (iGL) that binds very poorly to pre-F, thus high levels of somatic mutations are needed to gain high binding affinity with pre-F. Our observation helps to understand the evolution of RSV antibody during natural infection. Furthermore, by in silico prediction and experimental verification, we optimized 25-20 with KD values as low as picomolar range. Therefore, the optimized 25-20 represents an excellent candidate for passive protection against RSV infection.


Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus Vaccines , Respiratory Syncytial Virus, Human , Child , Humans , Viral Fusion Proteins/chemistry , Viral Fusion Proteins/genetics , Respiratory Syncytial Virus Vaccines/genetics , Respiratory Syncytial Virus, Human/chemistry , Respiratory Syncytial Virus, Human/genetics , Respiratory Syncytial Virus Infections/genetics , Respiratory Syncytial Virus Infections/prevention & control , Antibodies, Neutralizing , Antibodies, Viral
SELECTION OF CITATIONS
SEARCH DETAIL