PMID: 28514687
Title: Particulate Array of Well Ordered HIV Clade C Env Trimers Elicits Neutralizing Antibodies that Display a Unique V2 Cap Approach
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.
Date: 1970-08-22
Year: 2017
Journal: Immunity
PMID Author: Martinez-Murillo P, Tran K, Guenaga J, Lindgren G, Àdori M, Feng Y, Phad GE, Vázquez Bernat N, Bale S, Ingale J, Dubrovskaya V, O'Dell S, Pramanik L, Spångberg M, Corcoran M, Loré K, Mascola JR, Wyatt RT, Karlsson Hedestam GB
PMC Link #: PMC5528178

Media Contacts

Africa

Ethel Makila
+254 71 904 3142
EMakila@iavi.org

 

Europe

Hester Kuipers
+31 20 521 0343
HKuipers@iavi.org 

 

Global

Anita Kawatra
+1 212 847 1055
AKawatra@iavi.org 

 

India

Saif ul Hadi
+91 11 4737 6032
SulHadi@iavi.org 

 

United States

Rose Catlos
+1 212 847 1049
RCatlos@iavi.org