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Prefusion F-specific antibodies determine the magnitude of RSV neutralizing activity in human sera.

Sci Transl Med. 2015; 
Ngwuta Joan O,Chen Man,Modjarrad Kayvon,Joyce M Gordon,Kanekiyo Masaru,Kumar Azad,Yassine Hadi M,Moin Syed M,Killikelly April M,Chuang Gwo-Yu,Druz Aliaksandr,Georgiev Ivelin S,Rundlet Emily J,Sastry Mallika,Stewart-Jones Guillaume B E,Yang Yongping,Zhang Baoshan,Nason Martha C,Capella Cristina,Peeples Mark E,Ledgerwood Julie E,McLellan Jason S,Kwong Peter D,Graham Barn
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摘要

Respiratory syncytial virus (RSV) is estimated to claim more lives among infants <1 year old than any other single pathogen, except malaria, and poses a substantial global health burden. Viral entry is mediated by a type I fusion glycoprotein (F) that transitions from a metastable prefusion (pre-F) to a stable postfusion (post-F) trimer. A highly neutralization-sensitive epitope, antigenic site Ø, is found only on pre-F. We determined what fraction of neutralizing (NT) activity in human sera is dependent on antibodies specific for antigenic site Ø or other antigenic sites on F in healthy subjects from ages 7 to 93 years. Adsorption of individual sera with stabilized pre-F protein removed >90% of NT ac... More

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