Title : Immunogenicity and Cryo-EM structure of native-like HIV-1 Clade-C envelope trimers derived from a pediatric elite-neutralizer
Abstract:
Induction of broadly neutralizing antibodies (bNAbs) is a major goal in HIV-1 vaccine research. Elite neutralizers are rare HIV-1-infected individuals who develop broad and potent neutralizing antibody responses. Herein, we characterize a stabilized HIV-1 Clade-C envelope mimic, AIIMS 330, derived from an ART-naïve chronically infected pediatric EN. The AIIMS 330 Env was stabilized and engineered on SOSIP and NFL platforms, with multivalent presentation on ferritin nanoparticles. Biophysical analyses confirmed that the soluble and multivalent Env trimers closely resembled native structures, exposing multiple bNAb epitopes. Cryo-EM analysis revealed a stable prefusion closed conformation of the AIIMS 330 SOSIP trimer at 4.5 ? resolution. The Env variants displayed strong binding to bNAbs and minimal reactivity to non-nAbs. Immunization of rabbits with AIIMS 330, particularly in its multivalent NP’s form, elicited robust neutralizing responses against autologous viruses with limited heterologous breadth. These findings provide insights into the structural and immunogenic properties of Clade-C Envs, highlighting the potential of nanoparticle-based platforms to improve Env immunogenicity.
