Researchers identify antibodies able to kill most strains of HIV

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LOS ANGELES — An effective vaccine against the AIDS virus may have moved one step closer to reality, researchers said Thursday.

Federal researchers have identified a pair of
naturally occurring antibodies that are able to kill more than 90
percent of all strains of the AIDS virus, a finding they say could lead
to the development of new treatments for HIV infections and to the
production of the first successful vaccine against the virus.

HIV, the virus that causes AIDS, is notoriously
mutable, changing the composition of proteins on its surface with ease
to escape pressure from the immune system. This enables it to continue
infecting cells even after the appearance of antibodies targeting it —
and to avoid the relatively ineffective vaccines developed so far.

Hundreds of variants of the virus are now in
circulation around the world and the identification of so-called
broadly neutralizing antibodies that can block the bulk of them has
been the holy grail of HIV researchers.

To date, however, the best antibodies — immune
system proteins that fight infections — that researchers have found
block only 30 percent to 40 percent of all HIV strains. The
identification of antibodies that can block more than 90 percent of
strains could lead to what some researchers are dubbing a renaissance
in AIDS prevention and treatment.

The key to the new antibodies is that they bind to a site on the virus surface that rarely undergoes mutations.

“I am more optimistic about an AIDS vaccine at this point in time than I have been probably in the last 10 years,” Dr. Gary Nabel of the National Institute of Allergy and Infectious Diseases told
Reuters. He led the research reported Thursday in the online edition of
the journal Science.

Nabel and his colleagues isolated the antibodies
from the blood of a 60-year-old African-American gay man known as Donor
45. Using newly developed imaging and analytical techniques, they found
that the two antibodies, called VRC01 and VRC02, bind to a spike on the
surface of the virus. This spike interacts with a receptor called the
CD4 binding site on the surface of human cells, and when an antibody
binds to it, the virus cannot enter a cell.

Because the virus must use CD4 to enter cells, it
cannot tolerate mutations in the spike. The composition of the spike is
thus pretty much constant in all variants of HIV in circulation.

“The antibodies attach to a virtually unchanging
part of the virus, and this explains why they can neutralize such an
extraordinary range of HIV strains,” Dr. John R. Mascola of the NIAID, a co-author, said in a statement.

With the antibodies in hand, the team was able to
determine precisely how the HIV spike and the antibodies interact. They
were then able to produce a synthetic version of the spike that could
elicit the production of similar blocking antibodies in animal cells.

They are now testing the synthetic spike as a
possible vaccine in animals and hope to expand to human testing in the
relatively near future. The antibodies can also be reproduced by
biotechnology and used as a treatment for someone who is already
infected.

Researchers, who are already testing the antibodies
in infected animals, hope that at the very least the antibodies would
provide synergistic effects when used in conjunction with antiviral
drugs.

Other researchers, such as Dennis Burton of the Scripps Institute in the San Diego community of La Jolla,
have also discovered broadly neutralizing antibodies, although most of
the discoveries have not yet been published. Fortuitously, Mascola has
found, antibodies discovered by Burton block viral variants that are
not blocked by the antibodies reported Thursday.

Researchers thus hope that incorporating synthetic
chemicals that stimulate production of several different antibodies
might provide nearly complete protection against HIV.

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(c) 2010, Los Angeles Times.

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