A proof of concept for structure-based vaccine design targeting RSV in humans

被引：279

作者：

Crank, Michelle C. ^{[1
]}

Ruckwardt, Tracy J. ^{[1
]}

Chen, Man ^{[1
]}

Morabito, Kaitlyn M. ^{[1
]}

Phung, Emily ^{[1
,2
]}

Costner, Pamela J. ^{[1
]}

Holman, LaSonji A. ^{[1
]}

Hickman, Somia P. ^{[1
]}

Berkowitz, Nina M. ^{[1
]}

Gordon, Ingelise J. ^{[1
]}

Yamshchikov, Galina V. ^{[1
]}

Gaudinski, Martin R. ^{[1
]}

Kumar, Azad ^{[1
]}

Chang, Lauren A. ^{[1
]}

Moin, Syed M. ^{[1
]}

Hill, Juliane P. ^{[1
,5
]}

DiPiazza, Anthony T. ^{[1
]}

Schwartz, Richard M. ^{[1
,6
]}

Kueltzo, Lisa ^{[1
]}

Cooper, Jonathan W. ^{[1
]}

Chen, Peifeng ^{[1
]}

Stein, Judith A. ^{[1
]}

Carlton, Kevin ^{[1
]}

Gall, Jason G. ^{[1
]}

Nason, Martha C. ^{[3
]}

Kwong, Peter D. ^{[1
]}

Chen, Grace L. ^{[1
]}

Mascola, John R. ^{[1
]}

McLellan, Jason S. ^{[4
]}

Ledgerwood, Julie E. ^{[1
]}

Graham, Barney S. ^{[1
]}

机构：

[1] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[2] George Washington Univ, Inst Biomed Sci, Washington, DC 20052 USA

[3] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20852 USA

[4] Univ Texas Austin, Dept Mol Biosci, Coll Nat Sci, Austin, TX 78712 USA

[5] Cytek Biosci, Fremont, CA 94538 USA

[6] CRISPR Therapeut AG, Cambridge, MA 02139 USA

来源：

SCIENCE | 2019年 / 365卷 / 6452期

基金：

美国国家卫生研究院;

关键词：

RESPIRATORY SYNCYTIAL VIRUS; FUSION-GLYCOPROTEIN VACCINE; NEUTRALIZING ANTIBODIES; INFECTION; INFANTS; IMMUNIZATION; CHILDREN; TRIAL; RISK;

D O I：

10.1126/science.aav9033

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Technologies that define the atomic-level structure of neutralization-sensitive epitopes on viral surface proteins are transforming vaccinology and guiding new vaccine development approaches. Previously, iterative rounds of protein engineering were performed to preserve the prefusion conformation of the respiratory syncytial virus (RSV) fusion (F) glycoprotein, resulting in a stabilized subunit vaccine candidate (DS-Cav1), which showed promising results in mice and macaques. Here, phase I human immunogenicity data reveal a more than 10-fold boost in neutralizing activity in serum from antibodies targeting prefusion-specific surfaces of RSV F. These findings represent a clinical proof of concept for structure-based vaccine design, suggest that development of a successful RSV vaccine will be feasible, and portend an era of precision vaccinology.

引用

页码：505 / +

页数：35

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