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Promising HIV vaccine candidate found

Scientists in the US have identified a key defect in immune response to HIV and developed a possible treatment to rectify it

Scientists at University of Texas Houston Medical School in the US have identified an important immunological deficiency in HIV-infected patients and created a promising HIV vaccine candidate that rectifies the deficiency. The discoveries of Dr Sudhir Paul and his team are being backed by the not-for-profit organisation, Abzyme Research Foundation (ARF), which supports innovative research into the treatment and prevention of HIV/AIDS.

The candidate has been tested in mice and rabbits and found to be effective in inducing the production of protective antibodies that stopped the HIV from infecting human blood cells in laboratory tests.

Dr Paul and his colleagues discovered that HIV patients do not produce sufficient protective IgG antibodies that can attack the vulnerable CD4 binding site on the HIV. The virus binds to human host cells through this site to cause infection. The CD4 binding site is a small part of gp120, a protein found on the surface of HIV. Studies of mice injected with gp120 confirmed an insufficient IgG response to the CD4 binding site. Previous vaccine tests by other researchers used the gp120 protein itself without success in protecting against infection.

"Using an electron-seeking form of gp120, we triggered the production of the crucial IgG antibodies to the CD4 binding site in animals," said Dr Paul. "We believe this method is the key to developing an HIV vaccine."

The team found that chemical stimulation of the immune system by electron-seeking - or electrophilic - proteins is central to rectifying the defective antibody response to the CD4 binding site. Since the structure of the CD4 binding site is similar in all HIV strains, a globally effective HIV vaccine may be possible.

They developed a synthetic electrophilic vaccine candidate, E-VAC, which works by focusing the antibody response on the CD4 binding site. It is a synthetic portion of gp120 that successfully mimics the shape of the CD4 binding site expressed by the HIV virus. Administration of E-VAC to animals induced antibodies with enzymatic activity, or abzymes. Unlike traditional antibodies that neutralise the target on a 1:1 basis, each abzyme molecule can neutralise thousands of target molecules.

When administered to mice and rabbits, E-VAC induced the production of blood-borne IgG antibodies that blocked the infection of human cells by genetically divergent HIV-1 strains from across the world.

"We are backing the research of Dr Paul's team because his approach using abzymes shows enormous progress in creating an HIV vaccine," said Alan Kleiman, chairman of the board at ARF.

"Our foundation aims to drive discovery and innovation in the field of HIV research in hopes of one day eliminating the HIV/AIDS pandemic."

See more about the research at: www.abzymeresearchfoundation.org

21st July 2010

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