Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates

被引：62

作者：

Saunders, Kevin O. ^{[1
,6
]}

Nicely, Nathan I. ^{[2
,6
]}

Wiehe, Kevin ^{[2
,6
]}

Bonsignori, Mattia ^{[2
,6
]}

Meyerhoff, R. Ryan ^{[3
,6
]}

Parks, Robert ^{[2
,6
]}

Walkowicz, William E. ^{[7
]}

Aussedat, Baptiste ^{[7
]}

Wu, Nelson R. ^{[2
,6
]}

Cai, Fangping ^{[2
,6
]}

Vohra, Yusuf ^{[7
]}

Park, Peter K. ^{[7
]}

Eaton, Amanda ^{[1
,6
]}

Go, Eden P. ^{[11
]}

Sutherland, Laura L. ^{[2
,6
]}

Scearce, Richard M. ^{[2
,6
]}

Barouch, Dan H. ^{[14
]}

Zhang, Ruijun ^{[2
,6
]}

Von Holle, Tarra ^{[2
,6
]}

Overman, R. Glenn ^{[2
,6
]}

Anasti, Kara ^{[2
,6
]}

Sanders, Rogier W. ^{[13
]}

Moody, M. Anthony ^{[3
,5
,6
]}

Kepler, Thomas B. ^{[9
]}

Korber, Bette ^{[10
]}

Desaire, Heather ^{[11
]}

Santra, Sampa

Letvin, Norman L. ^{[8
]}

Nabel, Gary J. ^{[12
]}

Montefiori, David C. ^{[1
]}

Tomaras, Georgia D. ^{[1
,3
,4
,6
]}

Liao, Hua-Xin ^{[2
,6
]}

Alam, S. Munir ^{[2
,6
]}

Danishefsky, Samuel J. ^{[7
]}

Haynes, Barton F. ^{[2
,3
,6
]}

机构：

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

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

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

[4] Duke Univ, Sch Med, Dept Mol Genet & Microbiol, Durham, NC 27710 USA

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

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

[7] Sloan Kettering Inst Canc Res, New York, NY 10065 USA

[8] Harvard Med Sch, Boston, MA 02215 USA

[9] Boston Univ, Boston, MA 02215 USA

[10] LANL, Los Alamos, NM 87545 USA

[11] Univ Kansas, Lawrence, KS 66045 USA

[12] Sanofi, Cambridge, MA 02139 USA

[13] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands

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

来源：

CELL REPORTS | 2017年 / 18卷 / 09期

关键词：

HIV GLYCAN SHIELD; AFFINITY MATURATION; GLYCOSYLATION PROFILES; ENVELOPE GLYCOPROTEINS; IN-VITRO; POTENT; RECOGNITION; COMPLEX; 2G12; ENV;

D O I：

10.1016/j.celrep.2017.02.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans-a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors.

引用

页码：2175 / 2188

页数：14

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