The Chicago Tribune, Sunday, November 16, 1997
Ronald Kotulak, Tribune science writer.

Can the epidemic be stopped?

In theory, the answer is yes. An anti-AIDS vaccine could halt the spread of the infection in the same way that a vaccine wiped smallpox from the face of the globe in the late 1970s.

Nor is there any shortage of potential AIDS vaccines. In the U.S. alone, researchers have conjured up 27 experimental vaccines, ranging from those composed of harmless components of the AIDS virus to those consisting of the live virus itself in weakened form.

Why, then, are public health experts wringing their hands over the prospect that the AIDS epidemic will continue unabated, infecting up to 100 million people in the next 10 years?

The reason is that all the candidate vaccines are on hold. Most have been tested in animals and a small number of human volunteers. Results have been mixed, ranging from inconclusive to promising, though most of the experimental vaccines are considered safe.

Yet they remain in limbo, left hanging by the enormous effort to develop drugs to treat people who already have been infected.

Devising and developing vaccines is very complex and involves a great deal of guesswork, but the only way to find out whether a vaccine works is to give it to large numbers of volunteers. That's what happened to many of the vaccines that are now used to protect people against a variety of once-deadly diseases.

In the 1950s, when Jonas Salk was working on his polio vaccine composed of dead polio virus, he was severely criticized by many other scientists who condemned his research as "quackery." They said his dead virus wouldn't build immunity and that some live viruses would slip by the killing process and cause polio.

The critics insisted that Salk's vaccine should be shelved in favor of the experimental Sabin oral vaccine, which is made from a live, weakened virus. Sabin's vaccine would be safer and more effective, it was argued, even though it was years away from being ready. On the other hand, Salk's vaccine was ready to go.

The March of Dimes didn't wait around. It backed Salk's vaccine in the midst of an epidemic that was killing 3,000 American children each year and paralyzing many more. It was a striking example of a private agency taking the lead away from the federal government. After large-scale tests in humans, the Salk vaccine was pronounced a success in 1955. It was 70 percent effective in protecting children from developing polio.

Sabin's vaccine took seven more years to develop. If the March of Dimes had waited for it, thousands more children would have died.

But Salk's critics were proved right on one point: A batch of the Salk vaccine produced by Cutter Laboratories contained viruses that had not been killed in the vaccine-making process. Many of the children vaccinated with this defective batch developed polio.

Development of the AIDS vaccine is going through a similar round of second-guessing, fears and delays. The first AIDS vaccine was tested in people in 1987. But with only a handful of people tested, no conclusions could be drawn and it was not followed up. Since then 16 experimental vaccines have been tested in only about 2,000 healthy volunteers.

What is becoming increasingly unacceptable is that none of the vaccines has advanced to the critical next stage, which requires testing in hundreds or thousands of people. That must be done to find out whether any of the vaccines provide some degree of protection against the human immunodeficiency virus that causes AIDS.

"We have several preparations sitting on the shelf that could be effective vaccines," asserted Dr. Richard Marlink, executive director of the Harvard AIDS Institute. "They probably won't be 100 percent effective, but vaccine history tells us that that's usually the case with the first round of vaccines."

At the center of the impasse are scientific and philosophical differences of opinion. In scientific circles they are known as the "theorist" versus "empiricist" debate.

Vaccine proponents charge that the National Institutes of Health, which finances most AIDS research, including vaccine development, is in the theorist camp and has a severe case of cold feet. The NIH is so afraid of failure that the government is delaying large-scale trials until all the science about HIV is known and there is some guarantee that a vaccine would be successful.

NIH's reluctance to forge ahead with vaccine trials surfaced in 1994 when it canceled plans for major human trials on two of the first generation of AIDS vaccines. NIH said it had second thoughts, primarily about the lack of solid scientific evidence of the vaccines' effectiveness, despite tantalizing evidence in chimpanzees that the vaccines worked.

One of those vaccines is made up of part of the protein coat of the virus. In tests with chimps, the vaccine protected most from getting infected with the AIDS virus. Chimps usually don't develop AIDS symptoms, but they can be infected with the virus to produce a harmless infection. Although chimps are not a perfect model for testing AIDS vaccines, they are useful for determining whether a vaccine can stimulate immunity against the virus.

NIH's hesitant approach to AIDS vaccine development was sharply criticized in 1996 by the Vaccine Research and Development Area Review Panel. The panel, headed by Dani Bolognesi, director of Duke University's Center for AIDS Research, found that the institute's vaccine development programs were "in crisis." Lack of support, poor research, inadequate funding, insufficient leadership and little coordination with other countries were among the reasons cited.

On the other side of the vaccine argument are the doctors who treat AIDS patients. These so-called empiricists argue that desperate measures are in order. They want at least six of the candidate vaccines to undergo widespread trials immediately.

The doctors say they also must battle a growing complacency in this country stemming from the misconception that the AIDS epidemic has peaked.

Although death rates are declining among patients who can afford the drugs, minorities and ethnic groups are not benefiting from the medications. The rate of infection is increasing among women and heterosexuals. Furthermore, new drugs do not work for everyone and they may lose their effectiveness over time.

For the rest of the world, anti-AIDS drugs are out of reach. They will not be available to people in developing countries, such as in Africa, where 60 percent of the people in some communities are infected with the AIDS virus. Of the 28 million global infections, 65 percent are in sub-Saharan Africa and another 20 percent in countries of South and Southeast Asia. Moreover, experts predict the epidemic is about to explode in China, India and Russia.

Both sides in the now-or-wait debate want a safe and effective AIDS vaccine. They disagree on when and how to proceed.

The empiricists, the clinicians, include a Chicago-based group called the International Association of Physicians in AIDS Care, who recently focused a spotlight on the stalled vaccine research when 50 of its members volunteered to be injected with an experimental but potentially risky live, weakened AIDS vaccine. Three hundred more doctors since have joined them.

"I don't consider volunteering an act of heroism," said Dr. Charles F. Farthing, medical director of the AIDS Healthcare Foundation in Los Angeles.

Farthing, who has treated AIDS patients for 15 years and has seen the hopelessness and death the disease brings, said a vaccine is the only realistic means of combating the AIDS epidemic.

"I don't think that the risks to my own health from the proposed vaccine are great. But if they are, it's only right that scientists and doctors should be among the first to find that out. That's what they've done in the past, (serving as guinea pigs) and that's what we should continue to do," he said.

Vaccines work by using part of a germ, or a weakened version, to stimulate an immunological response against the real thing should it invade the body. The least effective vaccines are made up of inactive parts of the microbe. They stimulate the lowest level of immunity. Conversely, a live virus that is weakened to make it harmless provides the strongest immunity. Most vaccines are made of live but weakened infectious agents.

Vaccines traditionally must be considered on a risk versus benefit basis. For instance, the Sabin polio vaccine, because it is made from a live, weakened virus, is more effective than the Salk vaccine. But it carries a small risk of causing polio. Each year about eight cases are linked to the vaccine.

The experimental live, weakened HIV vaccine that the physicians are willing to try carries a risk of causing AIDS or perhaps cancer. But it also has the greatest chance of being the most effective.

This vaccine is made by clipping off four of the virus' nine genes. The idea is that in this living but weakened state the virus will induce immunity but not cause disease.

Support for that notion has come from two sources. People infected with a less deadly form of the AIDS virus have been shown to develop immunity against the more virulent variety. Secondly, a naturally mutated AIDS virus, missing one of the genes that also is cut out in the proposed weakened vaccine, does not appear to cause disease in humans.

The guinea pig doctors are talking to NIH officials about setting up a trial with the live vaccine, perhaps starting next year, that would involve five doctors. The purpose would be to see whether they develop antibodies and other forms of immunity to the virus. If they do, and don't develop AIDS symptoms, then larger numbers could be tested.

A different vaccine--and the newest one on the list--consists of only a few genes that have been removed from the AIDS virus. It is not considered a live virus vaccine. It is being tested in 30 volunteers at the University of Pennsylvania under the direction of Dr. David B. Weiner. The gene vaccine seems to protect chimps from AIDS infection and early results in the human trials are encouraging. Seven months after being injected with the viral DNA, the volunteers appear to be showing a broad-based immunological response to the virus.

In May, President Clinton called for an Apollo man-on-the-moon-style effort to develop an AIDS vaccine by 2007, a goal that appears to be unattainable, given the stalemate over research.

"We're not going to be on the moon in the vaccine world in 10 years if we don't really revamp our national effort," Marlink said.

"We're headed in the right direction. But we've got to increase the funding for vaccine research fivefold. We also need to go ahead with widescale testing and be willing to fail. We're not going to succeed if we're not willing to fail."

CAPTION: PHOTO (color): COUNTDOWN TO DISASTER. (Several faces and a syringe.) The photo on the front page was provided courtesy of the Journal of the International Association of Physicians in AIDS Care.

Copyright 1997/The Chicago Tribune. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Permissions Desk, The Chicago Tribune, 435 North Michigan Avenue, Chicago, IL 60611.
971116
CT971106

Always watch for outdated information. This article first appeared in 1997. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1997. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .