Consortium for HIV/AIDS Vaccine Development

Project Summary/Abstract (30 lines)
The overarching goal of this CHAVD is to develop a sequential HIV vaccine regimen that
induces sustained protective levels of broadly neutralizing antibodies (bnAbs) in humans. bnAbs
provide complete protection against HIV infection in preclinical models. We hypothesize that an
effective HIV vaccine will need to consistently induce bnAbs against 2-3 different sites on the
HIV Envelope glycoprotein (Env) of the virus in most (>90%) of vaccine recipients. Targeting
multiple sites is necessary to provide adequate coverage against the huge diversity of global
isolates. We propose a sequential strategy in which a series of designed immunogens guide
antibody responses from precursors to bnAbs. We are intensely developing and testing
immunogens. We have shown proof-of-principle of the sequential strategy in preclinical models
and our first three immunogens are entering manufacturing or clinical trials shortly.
The second major goal of this CHAVD is to generate immunogens that induce protective non-
neutralizing antibody (nnAb) responses that can either act alone or augment the protective
activity of bnAb responses. To accomplish this goal, we propose a tiered approach in which the
ability of nnAbs to capture infectious virions and to clear infected cells in vivo in two established
mouse models will be explored. The most effective nnAbs, alone and in combination with other
nnAbs and bnAbs, will then be assessed for their ability to protect nonhuman primates against
virus challenge. Protective nnAbs will be used as templates for immunogen design.
To support our translational effort, we have organized state-of the-art Manufacturing, Clinical
Trials Sample Analysis and Management and Operations units. In addition, we have established
twelve Scientific Research Support Units, headed by leaders in their fields, to underpin the
diverse scientific and technical capabilities required to execute our comprehensive and highly
integrated vaccine program
Finally, this CHAVD proposal is built upon a highly successful, innovative and efficient CHAVI-
ID program that has made major scientific contributions to the HIV vaccine field. The CHAVD
provides the opportunity to advance and translate these contributions into an HIV vaccine.

Grant Number: 5UM1AI144462-07
NIH Institute/Center: NIH
Principal Investigator: Dennis Burton