AIDS/Smallpox Vaccine OK in Early Test

An AIDS vaccine that uses a genetically engineered smallpox virus to boost anti-HIV immunity looks promising in early tests on humans.

In animal tests, the vaccine did not protect monkeys against infection with an AIDS virus. But vaccinated animals remained healthy -- and suffered no immune damage from the deadly virus.

Now, nine humans have received small doses of the vaccine: about one-tenth of the full dose. The vaccine was safe. And even at this tiny dose, it stimulated the kind of immune responses that protected monkeys.

The vaccine is the brainchild of Harriet Robinson, MD, chief of microbiology and immunology at Yerkes National Primate Research Center. Robinson is chief scientific advisor to GeoVax Labs Inc. of Atlanta, spun off from Emory University's vaccine center to market the vaccine.

"One of the big questions has been, 'Sure, you show promising immune responses in monkeys, but will you get it in people?' Now we have this result in humans, with just one tenth of a dose; it is very exciting," Robinson tells WebMD.

Michael Keefer, MD, professor of medicine at the University of Rochester, New York, helped test the vaccine through the NIH-sponsored HIV Vaccine Trials Network, for which he is associate director for scientific administration.

"We are very encouraged with Dr. Robinson's approach," Keefer tells WebMD. "She has some of the strongest data in her animal models as anyone. And the results look pretty good from this, the very earliest human trial of the vaccine."

AIDS Vaccine From Smallpox Vaccine

It's a two-part vaccine. First, a person gets two doses of a DNA vaccine carrying three important HIV genes called env, gag, and pol. Then a person gets two doses of a smallpox virus genetically engineered to carry the same three HIV genes.

The smallpox component of the vaccine makes it unique. The virus, called the modified Ankara virus or MVA, cannot replicate in humans and cannot cause disease. It was used in the waning days of the successful global smallpox eradication program to safely vaccinate some 120,000 people in Germany.

A side benefit of the GeoVax vaccine is that recipients will become immune to smallpox, should that virus return via bioterror attack or lab accident.

But the main reason for using the smallpox virus is that it is one of the most powerful stimulators of immunity known to man. And it seems that when the virus carries HIV genes, those powerful immune responses transfer to HIV as well.
AIDS Vaccine in 4 Years?

There are two basic kinds of immunity. Cell-based immune responses depend on killer blood cells that seek out and destroy infected cells. Antibody-based immune responses depend on antibodies that stick to germs or infected cells, inactivating them and marking them for destruction.

The GeoVax vaccine is designed to stimulate both kinds of immunity. The immune responses seen with one-tenth doses of the vaccine were cell-based responses. However, Robinson says she also expects to see anti-HIV antibodies in volunteers to get the full dose of the vaccine.

That study already is under way. Thirty volunteers are getting the full dose of the vaccine while six get mock injections. Results of that study should be known later this year.

Meanwhile, Robinson and colleagues are gearing up for a phase II study of the vaccine, which will involve hundreds of HIV-negative volunteers. Because of the promising phase I results, that trial has been moved up by a year and a half, Robinson says.

"The fact we are getting such good immune responses in humans is very encouraging," Robinson says. "We are moving forward, and if everything really goes absolutely smoothly, we could have a vaccine in four years."

That could happen, although in real-life vaccine and drug development, things rarely go so perfectly.

Two similar vaccines -- using adenovirus instead of smallpox virus -- are further alng than the GeoVax vaccine.

Drug giant Merck has a genetically engineered adenovirus vaccine that carries elements of the HIV gag, pol, and nef genes. That vaccine is being tested in some 3,000 people at high risk of infection in the U.S. and Africa.

The National Institutes of Health also has a genetically engineered adenovirus vaccine, carrying the HIV env, gag, and pol genes, which is used to boost DNA vaccination with the same genes. That vaccine is in early phase II trials involving hundreds of volunteers.

"With HIV vaccines, we are still at an early stage where we need to understand whether anything can influence HIV infection," Keefer says. "If we can get protection from anything, we will build on that. None of us in the vaccine world expect a home run right away."

After saying that, Keefer brightens. After 19 years of AIDS vaccine research, he calls himself an optimist.

"A home run could happen," he says. "It's happened before with other vaccines."

SOURCES: News release, GeoVax Labs Inc., Atlanta. Harriet Robinson, MD, chief of microbiology and immunology, Yerkes National Primate Research Center; senior researcher, Emory Vaccine Center; chief scientific advisor, GeoVax Labs Inc., Atlanta. Michael Keefer, MD, professor of medicine, University of Rochester, N.Y.; associate director for scientific administration, HIV Vaccine Trials Network.