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Novel genetics research advances possibility
of HIV vaccine
VANCOUVER/BOSTON - July 5, 2007 - A pioneering collaborative
study has discovered how the HIV virus evades the human body's immune
system. The research collaborative - involving scientists from the
British Columbia
Centre for Excellence in HIV/AIDS, Massachusetts General Hospital
(MGH), Microsoft Research and Los Alamos National Laboratory - used
highly computer-intensive, cutting-edge statistical research methods
to investigate how the HIV virus mutates to escape the body's immune
system.
Specifically, "HLA class 1" is a controlling part of
the human immune response. The ability of HIV to escape recognition
by HLA class 1 leaves the body incapable of finding and fighting
the virus.
The study, published in the July issue of PLoS Pathogens,
is the largest population-based investigation of how natural variations
in HLA class 1 can influence HIV genetic sequence, as well as the
first characterization of changes in multiple HIV genes in response
to HLA-associated evolutionary pressure.
Researchers successfully mapped sites within particular HIV genes
where variations can improve the virus's ability to escape immune
recognition, showing this is predictable based upon the HIV patient's
individual HLA class 1 profile.
"This is a novel and advanced description of how the human
immune system attacks the virus, and how it responds" says
Richard Harrigan, PhD, director of the Centre's Research Laboratories
and study co-author. "While we always knew the body attacks
the virus and the virus changes to dodge pressure, we're now more
exact in knowing how this happens in people."
While the study is valuable in helping the scientific community
understand how immune pressure impacts HIV, these findings hold
tremendous promise in terms of global HIV efforts, says Zabrina
Brumme, PhD, the study's lead author. "Achieving a more in-depth
understanding of the ways in which HIV mutates to avoid the human
immune system will help with the design of an HIV vaccine,"
says Brumme, who is now with the Partners
AIDS Research Center at MGH.
Data were collected from the British Columbia HOMER cohort, a large
group of chronically HIV-infected, treatment-naïve individuals
for whom HLA class-1 typing and HIV RNA genotyping were performed.
Microsoft Research provided personnel and advanced software tools
to perform highly sophisticated statistical analysis. Algorithms
developed by David Heckerman, lead researcher of the Machine Learning
and Applied Statistics Group at Microsoft Research and study co-author,
and his team allowed for more in-depth analysis of the data sets.
"We created the software tools to help researchers exploit
the power of computing to more quickly and accurately identify the
crucial elements of an effective HIV vaccine," said Heckerman.
The original idea for the development of these statistical methods
came from Bette Korber, PhD, at Los Alamos National Laboratory.
Korber and co-researchers Tanmoy Bhattacharya, PhD, and Marcus Daniels
worked with Heckerman in further developing the cutting-edge statistical
approach.
Study results demonstrate that population-based approaches could
complement smaller functional studies by providing a whole-gene
or whole-virus picture of immune escape. Previous B.C. Centre research
published in The Journal of Infectious Diseases investigated
the role of HLA class 1 variation on response to anti-HIV therapy.
"Moving forward, we'll be expanding our genetic research to
other HIV genes. We'll also be investigating the role of drug therapy,"
says Harrigan.
About Partners AIDS Research Center
The Partners AIDS Research Center was established in 1995 in response
to the continuing world-wide AIDS pandemic. The center serves both
Massachusetts General Hospital and Brigham and Women's Hospital,
the founding members of Partners HealthCare, and is a natural progression
of the more than twenty-year commitment by the clinicians and scientists
at those institutions to HIV and AIDS research and care.
About the B.C. Centre for Excellence in HIV/AIDS
Founded in 1992 by St. Paul's Hospital and the provincial Ministry
of Health, the B.C. Centre for Excellence in HIV/AIDS is a key provincial
resource seeking to improve the health of people with HIV through
the development, ongoing monitoring and dissemination of comprehensive
investigative and treatment programs for HIV and related diseases.
St. Paul's Hospital is one of seven care facilities operated by
Providence Health Care, Canada's largest faith-based health care
organization.
About Los Alamos National Laboratory
Los Alamos National Laboratory is a multidisciplinary research institution
engaged in strategic science on behalf of national security. The
Laboratory is operated by a team composed of Bechtel National, the
University of California, BWX Technologies, and Washington Group
International for the Department of Energy's National Nuclear Security
Administration.
Media Contacts: Sue
McGreevey, MGH Public Affairs
Glen Edwards, B.C. Center
for Excellence in HIV/AIDS
Physician Referral Service: 1-800-388-4644
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