Particulate Array of Well-Ordered HIV Clade C Env Trimers Elicits Neutralizing Antibodies that Display a Unique V2 Cap Approach.
Immunity
; 46(5): 804-817.e7, 2017 05 16.
Article
en En
| MEDLINE
| ID: mdl-28514687
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Anticuerpos Anti-VIH
/
VIH-1
/
Productos del Gen env del Virus de la Inmunodeficiencia Humana
/
Multimerización de Proteína
/
Anticuerpos Neutralizantes
Límite:
Humans
Idioma:
En
Revista:
Immunity
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Suecia