Understanding and Manipulating Anti-HIV Antibody Responses via Structural Methods

Abstract

Anti-HIV antibody responses offer one of very few potential routes towards a protective HIV vaccine; structural biochemistry methods such as crystallography and computational modeling can provide key insights for the design of candidate vaccine components and enhance the evaluation of complex experimental outcomes. Accordingly, described herein are four projects investigating antibody interactions with HIV: (1) the design of scaffolds incorporating the V1/V2 loop of HIV gp120 for the determination of its structure as bound to the broadly neutralizing anti-HIV antibody PG9, (2) the determination of antibody exposure for the protein components used in the RV144 vaccine trial, (3) crystallographic analysis of designed proteins presenting the b12 antibody's epitope as transplanted from HIV's gp120 envelope glycoprotein, and (4) biophysical characterization of b12's interactions with gp120 and development from its germline precursor antibody sequence using a panel of point mutants. These efforts, representing work on multiple aspects of potentially key importance in shifting basic science research on HIV vaccinology into an translational and ultimately clinical phase, are representative of current work in B cell vaccine research for both the HIV field and for work on other pathogens of current interest.