NEW YORK, NY, LA JOLLA and SOUTH SAN FRANCISCO, CA, SEATTLE, WA, August 17, 2011 --
A team of researchers at and associated with the International AIDS
Vaccine Initiative (IAVI), The Scripps Research Institute, the
biotechnology company Theraclone Sciences and Monogram Biosciences Inc.,
a LabCorp company, report in the current issue of Nature the isolation
of 17 novel antibodies capable of neutralizing a broad spectrum of
variants of HIV, the virus that causes AIDS.
The new antibodies, large protein molecules that bind to pathogens
and flag them for destruction, were isolated from blood serum samples
collected in a continuing global search for broadly neutralizing
antibodies (bNAbs) launched by IAVI. They should provide researchers
with a new set of targets for the design of vaccine candidates that can
elicit similar antibodies to protect people from contracting HIV. Some
of the bNAbs blocked HIV infection of cells as much as 10 to 100 times
as potently as previously discovered bNAbs.
"Most antiviral vaccines depend on stimulating the antibody response
to work effectively," said Dennis Burton, a professor of immunology and
microbial science and director of the IAVI Neutralizing Antibody Center
at The Scripps Research Institute in La Jolla, Calif. Professor Burton,
one of the senior authors of the study, is also a member of the Ragon
Institute, in Cambridge, Mass. "Because of HIV's remarkable variability,
an effective HIV vaccine will probably have to elicit broadly
neutralizing antibodies. This is why we expect that these new antibodies
will prove to be valuable assets to the field of AIDS vaccine
research."
Only a minority of people who are HIV-positive begin to produce bNAbs
after several years of infection. Animal studies suggest that such
antibodies could block HIV infection if they were elicited by a
preventive vaccine. Researchers prize bNAbs because their structural
and biochemical analysis can reveal how to achieve a preventive vaccine.
Specifically, scientists expect that they can use information about how
bNAbs bind to HIV to construct immunogens--the active ingredients of
vaccines--that elicit similar antibodies. The potency of bNAbs matter
because a highly potent antibody could confer such protection at
relatively low levels.
"Solving the neutralizing antibody problem is perhaps the greatest
challenge facing the field today," said IAVI's chief scientific officer,
Wayne Koff. "IAVI concluded many years ago that unlocking the
information stored in bNAbs was going to be essential to the fulfillment
of our mission--ensuring the design and development of broadly effective
AIDS vaccines. This is why we support several laboratories around the
world that are designing novel vaccine candidates on the basis of what
we're learning from such antibodies. We have no doubt that these new
bNAbs will contribute a great deal to our own immunogen design efforts
and, we hope, those of other researchers working on AIDS vaccines."
In that regard, the new bNAbs are encouraging. Many of them bind
hitherto unknown molecular structures, or epitopes, on the surface of
HIV. This means that they could significantly broaden the target options
researchers have in designing vaccines to elicit similar antibodies.
How the antibodies were discovered
The 17 new bNAbs described in the current Nature report were isolated
from four HIV-positive individuals. The effort, sponsored by IAVI, is
unprecedented in scale and distinguished by its emphasis on identifying
antibodies that neutralize subtypes of HIV circulating primarily in
developing countries. It had previously yielded three potent bNAbs, two
of which, PG9 and PG16, were isolated by this research team in 2009 and
described in the journal Science. Another bNAb was subsequently isolated
from these samples by researchers at the Vaccine Research Center of the
National Institutes of Health, who have also discovered a set of bNAbs
from separate blood samples using an entirely different approach.
Both the previous and current studies used Theraclone Science's
highly sensitive I-STAR™ technology to isolate the antibodies. The new
crop of bNAbs, like PG9 and PG16, was rescued from cell cultures derived
from single antibody-producing B cells used for antibody discovery and
development. Theraclone Sciences Executive Chair and Interim CEO, Steven
Gillis commented, "We're delighted that I-STAR has provided essential
support in identifying bNAbs that will contribute to advancing AIDS
vaccine development. In this project, and in our own infectious disease
and cancer programs, the I-STAR platform continues to demonstrate a
remarkably powerful ability to isolate rare antibodies with unique
properties. Theraclone values these collaborative opportunities in which
I-STAR can be used to help improve treatment for critical diseases."
Monogram Biosciences, which also participated in the discovery of PG9
and PG16, conducted the neutralization assays essential to isolating
the new bNAbs. The serum samples from which they were isolated represent
the top 1% of all such samples gathered by IAVI and its partners, in
terms of the number of HIV variants they neutralize and the potency with
which they do so.
"Monogram has developed a highly skilled scientific team capable of
taking on a variety of biomedical challenges," said Chris Petropoulos,
Vice President, Laboratory Corporation of America Holdings, Research and
Development, Monogram Biosciences. "Their expertise and innovation has
been invaluable to the discovery of these new antibodies. This research
illustrates the important role different sectors of the research and
health care community can play in supporting global health initiatives."
The analysis of the new antibodies also hints at how future vaccines
ought to be formulated to maximize their effectiveness. On the basis of
their analyses, the authors of the report conclude that AIDS vaccine
candidates that seek to effectively harness the antibody response should
probably attempt to elicit certain combinations of bNAbs if they are to
provide truly comprehensive protection from HIV.
The published study on the 17 new bNAbs is available online at www.nature.com
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HIV Vaccine Awareness Day is an annual observance day to recognize and thank the thousands of volunteers, community members, health professionals, and scientists who are working together to find a safe and effective HIV vaccine. It is also a day to educate our communities about the importance of preventive HIV vaccine research.
