The Vaccine Research Center (VRC) is striving to develop an improved HIV neutralizing antibody that prevents HIV infection in adult and pediatric populations at risk for HIV-1 infection. Advances in the identification of broadly neutralizing antibodies to HIV have raised new opportunities to prevent infection through the administration of antibodies that neutralize diverse strains of the virus. In 2010, scientists led by a team from the VRC 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.
These 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. Building upon its work with VRC01, the VRC has used structure-guided approaches to isolate multiple anti-CD4 binding site antibodies, solve their crystal structures, and use this information to design new vaccine immunogens. The VRC is also developing second-generation antibody products to test the concept of passive immunization in adults, using modifications that are intended to reduce the requirement for product while retaining the ability of the antibody to confer protection against infection by diverse strains. Testing of the initial VRC01 antibody is scheduled to enter a Phase I clinical trial in early 2013.
An ongoing clinical study, HVTN 505, is a proof-of-concept study of a VRC HIV product and evaluates whether the VRC candidate DNA/rAd5 prime-boost vaccination regimen can reduce acquisition of disease, and 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 are performed at the NIAID Vaccine Immunogenicity T-Cell and Antibody Laboratory (NVITAL) and in HVTN’s core laboratories, all of which are NIAID-supported immune assay programs.
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.
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Last Updated November 17, 2010