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Scripps research scientists determine structure of immune molecule that counteracts HIV strains
Date:6/1/2010

ferent kind of antibody architecture. We like to call it the 'hammerhead' because it resembles the head of a hammerhead shark. It reaches out from the main part of the antibody and it has two flat ends on top."

Co-author Laura Walker, a graduate student in the Scripps Research Kellogg School of Science and Technology, added, "This hypervariable loop (CDR3) that forms the novel subdomain is also unusually long for an antibody. Almost all of the antibodies we know to be broadly neutralizing against HIV have one unusual feature or another."

Pejchal notes that the study also revealed that PG16 was sulfated, suggesting possible mechanisms of action not usually seen in antibodies this effective against HIV.

While the scientists were unsuccessful so far in crystallizing PG16's sister molecule PG9, they were able to glean insight into its action from biochemical studies using both molecules. By switching a small (seven-amino acid) segment of the CDR3 subdomain of PG9 for a similar segment from PG16, the team changed the subset of HIV isolates neutralized by the antibody. This confirmed the loop in question was the "business end" of the antibody and suggested that it might be possible to create other interesting variants of the antibody by manipulating this region.

Seth Berkley, president and CEO of IAVI, which funded the study with the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institute of Health (NIH), noted, "These studies of PG16 have taught us a lot about how these neutralizing antibodies work. I am particularly excited by the possibilities these findings open up for AIDS vaccine development, since the breadth and potency of HIV neutralization achieved by PG16 is what we'd like to see in the antibodies elicited by a vaccine. IAVI and its researchers will continue to support the application of these findings to the design of novel immunogens against HIV. We hope that we will be able to translate the
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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