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HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design.

Authors :
Bricault CA
Yusim K
Seaman MS
Yoon H
Theiler J
Giorgi EE
Wagh K
Theiler M
Hraber P
Macke JP
Kreider EF
Learn GH
Hahn BH
Scheid JF
Kovacs JM
Shields JL
Lavine CL
Ghantous F
Rist M
Bayne MG
Neubauer GH
McMahan K
Peng H
Chéneau C
Jones JJ
Zeng J
Ochsenbauer C
Nkolola JP
Stephenson KE
Chen B
Gnanakaran S
Bonsignori M
Williams LD
Haynes BF
Doria-Rose N
Mascola JR
Montefiori DC
Barouch DH
Korber B
Source :
Cell host & microbe [Cell Host Microbe] 2019 Jan 09; Vol. 25 (1), pp. 59-72.e8.
Publication Year :
2019

Abstract

Eliciting HIV-1-specific broadly neutralizing antibodies (bNAbs) remains a challenge for vaccine development, and the potential of passively delivered bNAbs for prophylaxis and therapeutics is being explored. We used neutralization data from four large virus panels to comprehensively map viral signatures associated with bNAb sensitivity, including amino acids, hypervariable region characteristics, and clade effects across four different classes of bNAbs. The bNAb signatures defined for the variable loop 2 (V2) epitope region of HIV-1 Env were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine, and immunization of guinea pigs with V2-SET vaccines resulted in increased breadth of NAb responses compared with Env 459C alone. These data demonstrate that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens capable of eliciting antibody responses with greater neutralization breadth.<br /> (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1934-6069
Volume :
25
Issue :
1
Database :
MEDLINE
Journal :
Cell host & microbe
Publication Type :
Academic Journal
Accession number :
30629920
Full Text :
https://doi.org/10.1016/j.chom.2018.12.001