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

Authors :
Crank MC
Ruckwardt TJ
Chen M
Morabito KM
Phung E
Costner PJ
Holman LA
Hickman SP
Berkowitz NM
Gordon IJ
Yamshchikov GV
Gaudinski MR
Kumar A
Chang LA
Moin SM
Hill JP
DiPiazza AT
Schwartz RM
Kueltzo L
Cooper JW
Chen P
Stein JA
Carlton K
Gall JG
Nason MC
Kwong PD
Chen GL
Mascola JR
McLellan JS
Ledgerwood JE
Graham BS
Source :
Science (New York, N.Y.) [Science] 2019 Aug 02; Vol. 365 (6452), pp. 505-509.
Publication Year :
2019

Abstract

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.<br /> (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Details

Language :
English
ISSN :
1095-9203
Volume :
365
Issue :
6452
Database :
MEDLINE
Journal :
Science (New York, N.Y.)
Publication Type :
Academic Journal
Accession number :
31371616
Full Text :
https://doi.org/10.1126/science.aav9033