March 21, 2012
At the recent CROI in Seattle, antibody expert Dennis Burton compared HIV's envelope structure to an assemblage of Tootsie Pops. In this analogy, the parts of HIV's envelope that are susceptible to neutralizing antibodies are represented by the chocolate contained inside the Tootsie Pop, and the carbohydrate molecules that act as decoys (by inducing ineffective non-neutralizing antibody responses) are represented by the coating of candy that surrounds the chocolate filling. Last year on the blog I wrote about two studies exploring a new strategy for dealing with HIV's shielded envelope: using certain enzymes to digest -- essentially eat away -- the carbohydrate covering so that neutralizing antibody targets are revealed. One of the research groups pursuing this idea is that of James Binley at Torrey Pines Institute for Molecular Studies, and in a new paper titled "HIV-1 Virus-Like Particles Bearing Pure Env Trimers Expose Neutralizing Epitopes but Occlude Nonneutralizing Epitopes" in the Journal of Virology they report that they have now refined the approach sufficiently to create unshielded envelope proteins (known as trimers) that can be tested in animal models. The hope is that these envelope proteins will be able to reliably induce neutralizing antibodies, unlike the carbohydrate-clad versions that have been tested to date.
Richard Jefferys is the coordinator of the Michael Palm HIV Basic Science, Vaccines & Prevention Project Weblog at the Treatment Action Group (TAG). The original blog post may be viewed here.
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