"Next generation HIV vaccine design via the 2F5 epitope"
A protective vaccine against HIV will likely require elicitation of "broadly neutralizing antibodies" that neutralize a diverse array of HIV strains. Four broadly-neutralizing antibodies are known at present, each targeting a different conserved epitope on the virus. In this project, we focus on the broadly-neutralizing antibody 2F5 that targets an epitope in the membrane-proximal external region of HIV gp41. The project focuses on design of immunogens to ‘re-elicit’ 2F5-like neutralizing responses, and on redesign of 2F5 itself to improve our understanding of its mechanism of neutralization. Both aims will employ a combination of computational design and directed evolution.
Aim 1: Develop novel membrane-protein based immunogens that conformationally stabilize the 2F5 epitope in the context of a lipid membrane to best approximate the epitope environment on the virion.
Aim 2: Design and characterize variants of the 2F5 antibody to determine the importance of the length and composition of the Complementarity Determining Region H3 (CDR-H3) loop and of the affinity for the peptide epitope required for 2F5 neutralization of HIV.