PMID: 26372963
Title: Design and structure of two HIV 1 clade C SOSIP 664 trimers that increase the arsenal of native like Env immunogens
Abstract: A key challenge in the quest toward an HIV-1 vaccine is design of immunogens that can generate a broadly neutralizing antibody (bnAb) response against the enormous sequence diversity of the HIV-1 envelope glycoprotein (Env). We previously demonstrated that a recombinant, soluble, fully cleaved SOSIP.664 trimer based on the clade A BG505 sequence is a faithful antigenic and structural mimic of the native trimer in its prefusion conformation. Here, we sought clade C native-like trimers with comparable properties. We identified DU422 and ZM197M SOSIP.664 trimers as being appropriately thermostable (Tm of 63.4 °C and 62.7 °C, respectively) and predominantly native-like, as determined by negative-stain electron microscopy (EM). Size exclusion chromatography, ELISA, and surface plasmon resonance further showed that these trimers properly display epitopes for all of the major bnAb classes, including quaternary-dependent, trimer-apex (e.g., PGT145) and gp120/gp41 interface (e.g., PGT151) epitopes. A cryo-EM reconstruction of the ZM197M SOSIP.664 trimer complexed with VRC01 Fab against the CD4 binding site at subnanometer resolution revealed a striking overall similarity to its BG505 counterpart with expected local conformational differences in the gp120 V1, V2, and V4 loops. These stable clade C trimers contribute additional diversity to the pool of native-like Env immunogens as key components of strategies to induce bnAbs to HIV-1.
Date: 1970-08-22
Year: 2015
Journal: Proc. Natl. Acad. Sci. U.S.A.
PMID Author: Julien JP, Lee JH, Ozorowski G, Hua Y, Torrents de la Peña A, de Taeye SW, Nieusma T, Cupo A, Yasmeen A, Golabek M, Pugach P, Klasse PJ, Moore JP, Sanders RW, Ward AB, Wilson IA
PMC Link #: PMC4586835
Design and structure of two HIV-1 clade C SOSIP.664 trimers that increase the arsenal of native-like Env immunogens. Proc. Natl. Acad. Sci. U.S.A. 2015;112(38):11947-52 doi: 10.1073/pnas.1507793112

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