Natural antibodies may pave way for effective HIV vaccine

March 16th, 2009 - 11:52 am ICT by ANI  

London, March 16 (ANI): Scientists at The Rockefeller University say that they have identified a diverse team of antibodies in “slow-progressing” HIV patients, which can knock down the virus.
Research leader Michel C. Nussenzweig, Sherman Fairchild Professor and head of the Laboratory of Molecular Immunology, says that natural immune response in these exceptional patients suggests that an effective HIV vaccine may come from an approach involving a wide range of natural antibodies rather than an engineered super antibody.
“We wanted to try something different, so we tried to reproduce what’’s in the patient. And what’’s in the patient is many different antibodies that individually have limited neutralizing abilities but together are quite powerful,” Nature magazine quoted Nussenzweig, who also is a Howard Hughes Medical Institute investigator, as saying.
“This should make people think about what an effective vaccine should look like,” he added.
HIV strains mutate rapidly, making them especially wily adversaries of the immune system. However, a protein on the envelope of the virus called gp140, which HIV needs to infect immune cells, is shared almost universally among the diverging strains.
Previous studies have shown that four randomly engineered antibodies that block the activity of that protein prevent the virus from infecting immune cells in culture. But scientists have not succeeded in coaxing the human body into producing such antibodies as yet.
So Johannes Scheid, a visiting student in Nussenzweig’’s lab who is now a doctoral candidate, focussed on the antibodies produced by six people infected with HIV, whose immune systems put up an exceptionally strong fight.
Scheid joined forces with David D. Ho and Jeffrey V. Ravetch, scientists at Rockefeller’’s Center for Clinical and Translational Science and Rockefeller, to isolated 433 antibodies from the subjects blood serum that specifically targeted the envelope protein the chink in HIV’’s protean armour.
The researchers cloned the antibodies and produced them in bulk, mapped which part of the envelope protein each targeted, and gauged how effective each was in neutralizing the virus.
They found a new structure within the envelope protein called the gp120 core that had never been recognized as a potential target for antibodies.
“It’’s the first time that anyone has defined what is really happening in the B cell response in these patients,” says Scheid.
The study indicates that it is common for these antibodies to have neutralizing activity, says Nussenzweig.
The researcher, however, points out that each antibody alone has limited ability to fight the virus.
“Individually, they”re not as strong as the Famous Four,” says Nussenzweig, referring to the high-profile super antibodies on which several vaccine attempts have been based.
However, in high concentrations, a combination of the sets of antibodies cloned from the individual patients seemed to act as teams to knock down the virus in cell culture as well as any single antibody studied to date.
According to the researchers, the natural antibodies were also able to recognize a range of HIV strains, which suggests that their diversity may be an advantage over a single super antibody that focuses on only one part of the virus, which can mutate.
Based on their findings, the researchers came to the conclusion that research into vaccines that mimic this natural antibody response may pay off. (ANI)

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