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

被引：112

作者：

Bricault, Christine A. ^{[1
]}

Yusim, Karina ^{[2
,3
]}

Seaman, Michael S. ^{[1
]}

Yoon, Hyejin ^{[2
]}

Theiler, James ^{[2
,3
]}

Giorgi, Elena E. ^{[2
,3
]}

Wagh, Kshitij ^{[2
,3
]}

Theiler, Maxwell ^{[2
]}

Hraber, Peter ^{[2
]}

Macke, Jennifer P. ^{[2
]}

Kreider, Edward F. ^{[4
,5
]}

Learn, Gerald H. ^{[4
,5
]}

Hahn, Beatrice H. ^{[4
,5
]}

Scheid, Johannes F. ^{[6
,7
]}

Kovacs, James M. ^{[8
,9
,10
,11
]}

Shields, Jennifer L. ^{[1
]}

Lavine, Christy L. ^{[1
]}

Ghantous, Fadi ^{[1
]}

Rist, Michael ^{[1
]}

Bayne, Madeleine G. ^{[1
]}

Neubauer, George H. ^{[1
]}

McMahan, Katherine ^{[1
]}

Peng, Hanqin ^{[8
,9
]}

Cheneau, Coraline ^{[1
]}

Jones, Jennifer J. ^{[12
,13
]}

Zeng, Jie ^{[12
,13
]}

Ochsenbauer, Christina ^{[12
,13
]}

Nkolola, Joseph P. ^{[1
]}

Stephenson, Kathryn E. ^{[1
,14
]}

Chen, Bing ^{[8
,9
]}

Gnanakaran, S. ^{[2
,3
]}

Bonsignori, Mattia ^{[15
,16
]}

Williams, LaTonya D. ^{[15
]}

Haynes, Barton F. ^{[15
,16
,17
]}

Doria-Rose, Nicole ^{[18
]}

Mascola, John R. ^{[18
]}

Montefiori, David C. ^{[15
,19
]}

Barouch, Dan H. ^{[1
,14
]}

Korber, Bette ^{[2
,3
]}

机构：

[1] Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA

[2] Los Alamos Natl Lab, Los Alamos, NM 87545 USA

[3] New Mexico Consortium, Los Alamos, NM 87545 USA

[4] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA

[5] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

[6] Massachusetts Gen Hosp, Boston, MA 02114 USA

[7] Harvard Med Sch, Boston, MA 02114 USA

[8] Childrens Hosp, Div Mol Med, Boston, MA 02115 USA

[9] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA

[10] Univ Colorado, Dept Chem, Colorado Springs, CO 80918 USA

[11] Univ Colorado, Dept Biochem, Colorado Springs, CO 80918 USA

[12] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA

[13] Univ Alabama Birmingham, CFAR, Birmingham, AL 35294 USA

[14] Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Boston, MA 02114 USA

[15] Duke Univ, Duke Human Vaccine Inst, Sch Med, Durham, NC 27710 USA

[16] Duke Univ, Dept Med, Sch Med, Durham, NC 27710 USA

[17] Duke Univ, Dept Immunol, Sch Med, Durham, NC 27710 USA

[18] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20814 USA

[19] Duke Univ, Dept Surg, Sch Med, Durham, NC 27710 USA

来源：

CELL HOST & MICROBE | 2019年 / 25卷 / 01期

关键词：

HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; CD4; BINDING-SITE; STANDARDIZED ASSESSMENTS; CONFORMATIONAL EPITOPE; POTENT NEUTRALIZATION; ENVELOPE GLYCOPROTEIN; BROAD NEUTRALIZATION; AFFINITY MATURATION; LINEAGE;

D O I：

10.1016/j.chom.2018.12.001

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 Glade 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.

引用

页码：59 / +

页数：22

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