MI2025 – Edem Gavor

Title:
Consistent and Rapid Induction of Potent Broadly Neutralizing HIV V3-Glycan Antibodies in Rhesus Macaques

Abstract:
Outbred animal models of rapid and reproducible elicitation of potent, broadly neutralizing antibodies (bNAbs) against HIV-1 Envelope could advance vaccine research. We designed a simian-human immunodeficiency virus (SHIV.5MUT) bearing a V3-glycan epitope-targeting Envelope that elicited bNAbs within a year in 14/22 rhesus macaques (plasma neutralization breadth ≥50%; ID50 titers >1:1000), compared with 0/14 controls. As revealed by antibody/virus sequencing and polyclonal epitope mapping by cryo-EM, SHIV.5MUT first induced V1-directed antibodies that drove generation of shortened V1 loop escape variants, which then stimulated V3-glycan bNAb precursors. For mature bNAbs, Fab-Env cryo-EM structures revealed V3-recognition motifs resembling human bNAb counterparts. In summary, antibody-virus coevolution after infection with an epitope-targeting SHIV is a generalizable strategy for inducing bNAbs and can facilitate identification of prime and sequential boosting immunogens for HIV-1 vaccine development. Thus, my talk will focus on both the immunological and structural mechanisms of V3-glycan bNAb induction in rhesus macaques. Unpublished data.

Biography:
I am a dynamic individual who can quickly adapt to new environments and work collaboratively or independently. I have acquired research experience and core skills in molecular biology and biochemistry, including recombinant protein expression and purification, protein structure, and interaction studies using X-ray crystallography. During my tenure as a graduate student and postdoctoral research fellow at the National University of Singapore, my previous research centered on the structure-function studies of a group of mosquito-borne viruses. Moving forward, I am interested in applying integrative structural biology including cryoEM to studying immune responses to viral infections towards effective immunogen design and bnAbs/vaccine development.

Recently, I have become acquainted with cryo-electron microscopy. Currently, I am a staff scientist in the Bjorkman lab at the California Institute of Technology, focusing on the structure-function studies of HIV-1/SARS-CoV-2 envelope proteins’ interactions with broadly neutralizing antibodies (bnAbs) using cryoEM. It is my goal to become an independent and expert user of cryoEM.