Particulate Array of Well-Ordered HIV Clade C Env Trimers Elicits Neutralizing Antibodies that Display a Unique V2 Cap Approach

被引：81

作者：

Martinez-Murillo, Paola ^{[1
]}

Tran, Karen ^{[2
]}

Guenaga, Javier ^{[2
]}

Lindgren, Gustaf ^{[3
]}

Adori, Monika ^{[1
]}

Feng, Yu ^{[2
]}

Phad, Ganesh E. ^{[1
]}

Bernat, Nestor Vazquez ^{[1
]}

Bale, Shridhar ^{[2
]}

Ingale, Jidnyasa ^{[2
]}

Dubrovskaya, Viktoriya ^{[2
]}

O'Dell, Sijy ^{[4
]}

Pramanik, Lotta ^{[1
]}

Spangberg, Mats ^{[5
]}

Corcoran, Martin ^{[1
]}

Lore, Karin ^{[3
]}

Mascola, John R. ^{[4
]}

Wyatt, Richard T. ^{[2
]}

Hedestam, Gunilla B. Karlsson ^{[1
]}

机构：

[1] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17177 Stockholm, Sweden

[2] Scripps Res Inst, Dept Immunol & Microbiol, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

[3] Karolinska Inst, Dept Med, Immunol & Allergy Unit, S-17177 Solna, Sweden

[4] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[5] Karolinska Inst, Astrid Fagraeus Lab, Comparat Med, SE-17177 Stockholm, Sweden

来源：

IMMUNITY | 2017年 / 46卷 / 05期

关键词：

IG KNOCKIN MICE; BINDING-SITE; VACCINE DESIGN; B-CELLS; ENVELOPE; IMMUNIZATION; RESPONSES; RECEPTOR; REDESIGN; FEATURES;

D O I：

10.1016/j.immuni.2017.04.021

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The development of soluble envelope glycoprotein (Env) mimetics displaying ordered trimeric symmetry has ushered in a new era in HIV-1 vaccination. The recently reported native, flexibly linked (NFL) design allows the generation of native-like trimers from clinical isolates at high yields and homogeneity. As the majority of infections world-wide are of the clade C subtype, we examined responses in non-human primates to well-ordered subtype C 16055 trimers administered in soluble or high-density liposomal formats. We detected superior germinal center formation and enhanced autologous neutralizing antibodies against the neutralization-resistant (tier 2) 16055 virus following inoculation of liposome-arrayed trimers. Epitope mapping of the neutralizing monoclonal antibodies (mAbs) indicated major contacts with the V2 apex, and 3D electron microscopy reconstructions of Fab-trimer complexes revealed a horizontal binding angle to the Env spike. These vaccine-elicited mAbs target the V2 cap, demonstrating a means to accomplish tier 2 virus neutralization by penetrating the dense N-glycan shield.

引用

页码：804 / +

页数：21

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