The IHV Division of Vaccine Research is dedicated to the development of a safe and effective vaccine against HIV-1. Research in the division focuses on the basic virology, immunology, cell biology, and structural biology of the outer HIV-1 envelope glycoprotein, gp120. This research has led to the development of a conformationally constrained gp120 immunogen, designated as FLSC (Full Length Single Chain), which is the lead AIDS vaccine from the institute. The FLSC vaccine is now on target for evaluation in a Phase I clinical trial in the summer of 2015 where it is the “first in human” test of this vaccine concept. In addition to the FLSC vaccine, Division research focuses on the mechanisms of protective immunity elicited by FLSC and other HIV-1 vaccines. Our emphasis is on understanding the role of Fc-mediated effector function in protection mediated by broadly neutralizing antibodies, weakly neutralizing antibodies, and non-neutralizing antibodies. Our approach is to seek understanding of antibody-mediated protection at the physicochemical level with the goal of improving immunogenicity of FLSC and other HIV-1 vaccines. In addition to understanding the mechanism of antibody-mediated protection Division researchers are also approaching the connected problems of poor antibody persistence to gp120-based vaccines and the ability of vaccine-elicited CD4+ T cells to counter antibody mediated protection by providing additional targets for HIV-1 replication.