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Annual and Interim Progress Report Summaries

Principal Investigator: Robert Gallo

Project: Sterilizing Protection Elicited by an HIV-1 Vaccine

  
Submitted September 4, 2012

Our program tests the hypothesis that antibodies to epitopes of the co-receptor binding domain (CD4i epitopes) can mediate sterilizing protection against HIV-1. Two active immunization projects and one passive immunization project are underway to test this hypothesis. The first active immunization project tests the hypothesis that parenteral immunity leads to sterilizing protection against SHIV. This hypothesis will be tested by co-immunizing rhesus macaques with DNA and protein formulations of a single chain gp120-CD4 complex (rhFLSC). This protocol has been shown to sustain systemic antibody responses at high levels. The second active immunization study will test the hypothesis that mucosal immunity can confer sterilizing protection against SHIV. This hypothesis will be tested using a vesicular stomatitis virus (VSV) mucosal vaccine to elicit mucosal immunity to rhFLSC. Rhesus macaques will be primed systemically with a DNA vaccine encoding rhFLSC and boosted by rhFLSC-VSV by parenteral and mucosal routes to determine whether mucosal immunity confers protection against SHIV challenge. The passive immunization project will determine whether CD4i monoclonal antibodies (mAbs) can protect against SHIV challenge. We have developed a set of mAbs that will be evaluated in vivo to test this hypothesis. One of these mAbs is potently neutralizing whereas another is not. However, the latter mAb mediates much stronger Fc-mediated effector function than the former mAb. Both will be evaluated in wild-type forms and forms in which Fc-mediated effector function is abrogated. Collectively, these studies will test the hypothesis that CD4i epitopes are targets of protective immunity against HIV-1.

Submitted September 8, 2011
Submitted January 11, 2011 (interim report)
Submitted August 30, 2010
Submitted April 15, 2010 (Interim Report)
Submitted August 27, 2009
Submitted February 2, 2009 (Interim Report)
Submitted July 1, 2008
 
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