Global HIV Vaccine Development
The Vaccine Research Center (VRC) has developed a prime-boost strategy using a multiclade DNA plasmid vaccine for prime vaccination and a recombinant adenoviral vector vaccine (rAd5) for booster vaccination. This product concept has been evaluated in Phase I and Phase II studies in over 1,000 subjects in collaboration with three clinical network partners in both domestic and international settings. These include the NIAID HIV Vaccine Trials Network (HVTN), the U.S. Military HIV Research Program (USMHRP), and the International AIDS Vaccine Initiative (IAVI). HVTN has study sites in the United States, South Africa, Jamaica, Haiti, and Brazil; USMHRP has study sites in Kenya, Uganda, and Tanzania; and IAVI has study sites in Rwanda and Kenya.
These studies have culminated in a test-of-concept Phase II efficacy study that is being conducted in North America with HVTN. The HVTN 505 study began in 2009 and evaluates whether the VRC candidate DNA/rAd5 prime-boost vaccination regimen can reduce viral load in subjects who become infected despite vaccination. Viral load is being tested as a surrogate marker for disease progression along with other clinical and virological endpoints. It will be analyzed together with immune response data to identify potential correlates of protection. Immune assays for the Phase II studies will be performed at the NIAID Vaccine Immunogenicity T-Cell and Antibody Laboratory (NVITAL) and in HVTN core laboratories, both NIAID-supported immune assay programs.
In parallel with the test-of-concept study to determine whether vaccine-induced T cell responses can provide efficacy, preclinical discovery work is proceeding on structure-based design of new immunogens to induce broadly neutralizing antibodies. In addition, new antigen designs and alternative gene-based vectors are being developed to improve vaccine-induced T cell responses, and alternative delivery approaches are being explored to induce better mucosal immunity.
In significant news, scientists led by a team from the VRC have discovered two potent human antibodies that can stop more than 90 percent of known global HIV strains from infecting human cells in the laboratory, and have demonstrated how one of these disease-fighting proteins accomplishes this feat. These antibodies could be used to design improved HIV vaccines or could be further developed to prevent or treat HIV infection. Moreover, the method used to find these antibodies could be applied to isolate therapeutic antibodies for other infectious diseases as well.
The scientists found two naturally occurring, powerful antibodies called VRC01 and VRC02 in an HIV infected individual's blood using a novel molecular device they developed that hones in on the specific cells that make antibodies against HIV. The device is an HIV protein that the scientists modified so it would react only with antibodies specific to the site where the virus binds to cells it infects. The scientists found that VRC01 and VRC02 neutralize more HIV strains with greater overall strength than previously known antibodies to the virus.
The researchers also determined the atomic-level structure of VRC01 when it is attaching to HIV. This has enabled researchers to define how the antibody works and to precisely locate where it attaches to the virus. With this knowledge, they have begun to design components of a candidate vaccine that could teach the human immune system to make antibodies similar to VRC01 that might prevent infection by the vast majority of HIV strains worldwide.
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