From a Form of AIDS

By Boyce Rensberger

Scientists working toward an AIDS vaccine have shown for the first time that

it is possible to protect monkeys against the simian version of AIDS by using a

new kind of vaccine made not with the whole virus itself but with a mere

protein molecule copied from the virus.

Advances on monkey AIDS are significant because early experiments must be

done on animals and the simian immunodeficiency virus (SIV), a close relative

of the human immunodeficiency virus (HIV), is the only one that causes an

AIDS-like disease in monkeys.

Leading AIDS vaccine researchers were mixed in their reaction to the

development, which is reported in Friday's issue of the journal Science.

One called it ``reassuring'' to learn that vaccines made from virus parts,

or subunits, can work. Many researchers worry that a vaccine made from whole

AIDS viruses, even if modified so as not to cause disease, might still prove

dangerous. But another scientist took a more pessimistic view, saying the

experimental vaccine has been shown to work only under ideal laboratory

conditions.

The vaccine has been tested only against the original strain used to make

it. The human AIDS virus comes in thousands of forms and some experts fear that

no single vaccine can protect against all.

The SIV vaccine was made using a relatively new strategy that is being tried

for a variety of diseases. Conventional vaccines contain the microbe that

causes the disease, either killed or weakened so that it cannot harm the host.

The cells of the immune system ``see'' the protein molecules that cover the

intruder's surface and make other molecules, called antibodies, that bind only

to those proteins, a key step in destroying microbes that arrive later.

In the new vaccine strategy, researchers used recombinant DNA technology to

snip out the SIV gene for making a surface protein called gp160. Then they

spliced that gene into the genetic material of vaccinia viruses. This is the

virus strain once used as smallpox vaccine.

In the SIV vaccine, the genetically altered vaccinia viruses obey the SIV

gene, make the SIV protein and install it on their outer coats. Monkeys

vaccinated with the altered viruses simultaneously developed antibodies against

any microbe carrying smallpox proteins and the one SIV protein.

The researchers, led by Shiu-Lok Hu of Bristol-Myers Squibb Pharmaceutical

Research Institute in Seattle, vaccinated four macaques with the modified

vaccinia. Sixty-two weeks later, the monkeys got a booster shot of isolated

gp160 protein. Eight weeks later they got a second booster.

Four weeks after the second booster, researchers injected the monkeys with

live SIV. Four unvaccinated monkeys also got SIV injections. Within weeks the

control monkeys all became infected. None of the four that were vaccinated

became infected. Even a year later, all four remained virus-free and healthy.

``Taken together,'' Hu and his colleagues at the University of Washington,

Duke University and the National Cancer Institute wrote in their report,

``these results indicate that a `sterilizing immunity' against challenge

infection was achieved in the immunized animals.''

``Sterilizing immunity,'' in which not a single invading virus is allowed to

survive, is considered essential for an AIDS vaccine to be truly effective.

Researchers had been skeptical that such a thing was possible. No vaccine now

in use is capable of wiping out every virus that gets into the body. Instead,

they help keep the invaders' numbers low while the immune system gets itself

into high gear. Only then are the invaders wiped out.

Dani P. Bolognesi of Duke, a leading AIDS vaccine researcher not involved in

the report, said Hu's findings ``give us some confidence that this subunit

approach can work. The others produced lots of antibodies but they didn't

protect the animals. It's not clear why this one worked and the others didn't.''

Ronald C. Derosiers, a vaccine researcher at Harvard Medical School, said

immunity from subunit vaccines declines rapidly with time and that while Hu's

team got good results by challenging the monkeys just weeks after a booster

shot, it remained to be seen whether ``sterilizing immunity'' would persist for

the years that would be needed in a real vaccine.