WASHINGTON
- AIDS researchers reported on Monday they had designed a vaccine
that they believe may do what no other vaccine has done before -- protect
people from infection with the virus.
So far the team at the Institute of Virology at the University of
Maryland has only tested monkeys. And they note that people trying to design
a vaccine against the AIDS virus have repeatedly failed.
But they think their design, based on the mechanism the virus uses to
attach to the immune cells it targets, is the best yet.
"In several animals, including monkey, we were able to generate
neutralizing antibodies that are not type-specific but broadly cover various
types of HIV," Dr. Robert Gallo, who helped discover the AIDS virus and who
heads the institute where the work was done, said in a telephone interview.
Making a vaccine against HIV is difficult because the virus integrates
itself into cells, and because it attacks the very immune cells that are
normally stimulated by a vaccine.
Although dozens of vaccines are in various stages of development, no one
thinks a truly protective vaccine has been designed. At best, doctors now
hope that one or more of the vaccines may simply help people to live a
little longer with the virus, or perhaps to reduce the ease with which it is
transmitted from person to person.
But with 40 million people infected, and no cure in sight, the need is
dire. AIDS has already killed 25 million people.
The earliest vaccine approaches used the so-called envelope protein gp120
found on the surface of HIV. The hope was that if the body's immune system
could be trained to recognize gp120, antibodies would attack the virus
whenever it appeared and neutralize it.
But it did not work well. VaxGen has a vaccine based on this approach in
phase III trials, the last stage of development before a vaccine is
licensed, but AIDS experts doubt it will protect large populations against
infection.
QUICKLY MUTATING VIRUS
Gallo said one problem is that such vaccines work very specifically
against the type of virus used in the lab. HIV mutates quickly and studies
suggest the gp120 is very different across strains -- different enough to
resist immunization.
His institute's team, writing in the Proceedings of the National Academy
of Sciences, said they tweaked this approach.
Their vaccine uses gp120, but with a twist.
"When HIV infects a cell, gp120 latches on to CD4," Gallo said. CD4 is a
cell receptor, a kind of cellular doorway, found on the immune system
T-cells that HIV infects.
"It changes shape when it does that."
The team, led by Timothy Fouts, have broken the gp120 off the rest of the
virus as it attaches to CD4. They combined the two joined pieces, CD4 and
gp120, to make the vaccine.
"The belly of the beast may be exposed at this point in time," Gallo
said.
Tests in macaque monkeys showed they produced antibodies when inoculated
with the vaccine. In laboratory dishes, these monkey antibodies neutralized
most of the main strains, or clades, of HIV, including HIV-A, B, C, D and E.
The subtypes differ from one another in about 30 percent of their genetic
sequence. Subtype B is found mostly in Europe, the Americas and Japan while
A, C, D and E are spreading in Africa and Asia, so a vaccine designed in the
United States may not work to protect Africans, who are the hardest hit by
AIDS.
The next step is to vaccinate monkeys and then see if they are protected
from infection by the monkey version of HIV, called SIV, or from an
engineered version of the two viruses called SHIV.
"The strategy designed here has worked in laboratory test systems and I
have no reason to believe that man should be an exception but one doesn't
make claims without data," Gallo said.