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

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2017 May 18

PMID 28514687

Citations 67

Authors

Paola Martinez-Murillo

Karen Tran

Javier Guenaga

Gustaf Lindgren

Monika Adori

Yu Feng

Ganesh E Phad

Nestor Vazquez Bernat

Shridhar Bale

Jidnyasa Ingale

Viktoriya Dubrovskaya

Sijy ODell

Lotta Pramanik

Mats Spangberg

Martin Corcoran

Karin Lore

John R Mascola

Richard T Wyatt

Gunilla B Karlsson Hedestam

Affiliations

Soon will be listed here.

Abstract

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.

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