Therapeutic Vaccines: The Return of Remune
Introduction to Vaccine Therapy
When Jonas Salk announced he had a vaccine for AIDS in 1987, people had never heard about "therapeutic vaccines." Vaccines were things people took to protect themselves from diseases, like polio or measles. But in real life, no vaccine ever actually protects anyone from getting infected with a germ -- it just helps make sure that the immune system can destroy the germ so fast that most of the time people are not even aware that a germ has even attacked.
Long before the age of antivirals, antibiotics, and antifungicides, many people were working hard to find ways to use vaccines to treat people who were already sick with infectious diseases. Louis Pasteur had figured out that you could vaccinate someone who had been bitten by a rabid dog several days after the germs had entered the body, and as long as you got the immune system revved up high enough to kill the germs before the brain was infected, you could stop the person from becoming ill.
And it had been noticed that even when people were not protected completely from a disease that sometimes, vaccines could keep the illness from becoming a serious one. For example, giving the measles vaccine after the measles virus enters the body can prevent disease from the virus, or at least make the disease much milder. Using a vaccine to help the body AFTER it has been attacked by a germ is called "vaccine therapy" or "therapeutic vaccination."
Why Vaccine Therapy for HIV?
The reason that many people decided to try out vaccine therapy for HIV in the 80's and early 90's was because it made sense given the nature of the disease. When the body is attacked by a germ, it responds immunologically. In the case of HIV, immediately after a person is infected with the virus, the amount of virus increases dramatically -- but the immune system is able to get it way down very quickly and keep the amount of virus contained for years. Getting the body to do a better job of fighting HIV made a lot of sense.
One way to tell that the body is sensitized to fighting a disease is by putting a little bit of the dead germ or parts of the germ under the skin. If the body starts to fight this little bit of dead germ under the skin, a bump will form, and this test of the body's ability to "recognize" the enemy germ's antigens and fight it is called "delayed type hypersensitivity reaction" or DTH. Much to everyone's surprise, people infected with HIV show very little DTH reaction to HIV! It is as if the virus does something to the immune system to cause it to "forget" that HIV is an enemy loose in the body. Because of this, Jonas Salk referred to HIV as the "Alzheimer's of the Immune System."
It made sense then to try to re-sensitize the body, which had done so well in the beginning driving down the tens of billions of HIV particles to a very low number (called the viral set point) and to see if by re-sensitizing the body using a vaccine made of dead HIV, the body might start to fight HIV more aggressively. However, a large national study of this with one vaccine "rgp 160," a vaccine made of the outside sugar coating of the virus called the "envelope" of the virus, tested by the U.S. Army, did not work to better control HIV growth.
One theory on why it didn't work better is that the envelope, the outside cover of the virus, changes a lot or "mutates," and as a result, the body might not be able to keep up with the changes. In other words, the immune system might be looking for one kind of virus cover while the virus was dressed up in new and different sugar clothing. However, the Salk vaccine, now known as Remune, made up only of the inside of the virus, might work because the inside of the virus does not change.
Thus far, from the large national trial (the 806 trial) that has been conducted, there is little conclusive evidence on what this vaccine can do. A randomized carefully done sub-study of this big trial shows that people on the vaccine had a little less virus and a few more T-cells. This change was too small to convince scientists and physicians that the vaccine was working.
Return of the Vaccines
Much to the surprise of scientists and activists alike, the use of antiviral cocktails leads to the body producing new, so-called "naive" T-cells.
Normally, the body has many different kinds of T-cells; each designed to fight different kinds of illnesses. It was originally thought that once HIV had destroyed the kind of T-cells that can fight a particular disease, the body could never regain the ability to fight the illness successfully. However, some of the new, naive T-cells may be able to fight those diseases, and vaccines might be able to speed up the process by causing them to make lots of copies of themselves creating what immunologists call "memory." One aspect of this exciting idea is that some of the new T-cells might be able to be taught to fight HIV itself, thus helping to get HIV under better control than with antivirals alone, and curing the "memory" problem that HIV causes the immune system to have.
Early Tests of Remune and HAART
Although Remune has been tested in many people, and although there are other vaccines which might also work in getting the body to fight HIV, Remune is the first to go into large national trials to see if it can help antivirals by getting the immune system to better control HIV. The first exciting data from a test of this idea was reported by Fred Valentine at New York University. He and his colleagues took a group of people with HIV and vaccinated half with Remune and the other half with a placebo injection. By doing this, he discovered that those patients who got the vaccine had T-cells, which recognized HIV. Those who received the placebo did not.
The reason this is so exciting is that when we study people with HIV who do well with no treatment and whose virus looks pretty average, what we find is that they have T-cells which recognize HIV, just like the people in the Valentine NYU study who took the vaccine. The obvious next question is: do people who use an HIV vaccine along with HAART do better in the long run? Are they in fact more like the "long term non progressors"? Soon there will be a large (more than 400 person) trial to test out this very question about Remune. The trial will see if those people who take Remune are less likely to have their drugs fail them than those who do not.
If you are interested in joining a trial using a vaccine, just call 1-800-Trials A to find out about any ACTG trial, or to get involved in a trial of Remune, call 1-877-858-7783. If you live in New York City and want to get involved in a treatment interruption trial involving both an HIV vaccine and IL-2, call Fran Spodek at (212) 746-4464.
Two uniquely informative and easy to understand educational pieces on immune-based therapies and IL-2 will be available in mid-June 2000. Community Prescription Service (CPS), the HIV positive owned and operated mail-order prescription service is producing the "Immune City" issue of InfoPack (bound by POZ) and a booklet called "Immune Restoration in HIV." To obtain free copies, call CPS at (800) 842-0502 or go to their website, www.prescript.com, for download of both.
David Scondras is the founder and chairman of Search For A Cure. Scondras developed the nationally recognized HIV treatment series, Reasons for Hope. All articles in the series are reviewed by expert HIV doctors and scientists and an HIV positive and negative focus group to ensure both accuracy and understandability.
Community reviewers include: Matthew Daloisio, Stuart Pynn, Dede Ketover and Robert Krebs.
The Scientific Review Panel for this article includes: Dr. Alfred DeMaria, Massachusetts Department of Public Health; Dr. Kendall Smith of Cornell University Medical School, Dr. Ronald Mitsuyasu of UCLA, and Dr. Fred Valentine of New York University Center For AIDS Research.
If you have any questions or would like to receive the Reasons For Hope series, contact Search For A Cure at 34 Edgerly Road #1, Boston, MA 02115 or call Search For A Cure at 617-536-2474 or fax 617-266-0051, or e-mail at email@example.com. Visit our Web site at www.searchforacure.org
Search For A Cure is a not for profit organization providing education, promoting access & advocating the basic human right to safe and effective treatment for all people living with AIDS.