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The fab crystal structure and surface representations from 3BNC60, one of the most potent anti-HIV antibodies isolated in the study. Image: Ron Diskin/Caltech
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Each time a virus invades a healthy individual,
antibodies created by the body fight to fend off the intruders. For some
viruses, like HIV, the antibodies are very specific and are generated too
slowly to combat the rapidly changing virus. However, in the past few years,
scientists have found that some HIV-positive people develop highly potent
antibodies that can neutralize different subtypes of the HIV virus.
Now, a study involving researchers at Caltech points to
the possibility of using these neutralizing antibodies in the development of a
vaccine. The paper, published in Science
Express, describes a group of novel antibodies that were isolated
from HIV-infected individuals using a new cloning approach.
These antibodies are the most potent anti-HIV antibodies targeting
the CD4 binding site—a functional site on the surface of HIV needed for cell
entry and infection—that have ever been identified, says Ron Diskin, a
post-doctoral scholar at Caltech who worked on the paper. David Ho (BS '74),
scientific director of the Aaron Diamond AIDS
Research Center
in New York, also contributed to the study,
which was led by researchers at Rockefeller
University.
At Caltech, the researchers conducted structural studies
and were able to show, based on similarity to a previously known antibody
(VRC01), that the new antibodies indeed target the CD4 receptor binding site.
CD4 positive cells are the point of HIV infection and where the virus
multiplies.
This study is important for several different reasons,
says Diskin. "First, it provides extremely useful reagents that can be
used for passive immunization to treat infected individuals," he says.
"Second, it demonstrates that a comparable and highly effective anti-HIV
immune response was elicited in different individuals, which strongly supports
the idea that an effective vaccine will be feasible to develop."
Next, researchers at Caltech will address the structural
mechanisms that make those antibodies so potent. In fact, they are currently
investigating those structural aspects of the neutralization mechanisms.
"We're very excited to have
the opportunity to use structural biology to learn what makes these new
antibodies so potent against HIV," says Pamela Bjorkman, Caltech's
Delbruck Professor of Biology and a co-author of the study. "We hope that
visualizing how these antibodies interact with HIV proteins will allow the design
of even more potent anti-HIV reagents and provide critical information for
vaccine design."
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