Feature

A ray of light in the dark

Israeli researchers develop vaccine that enables recovery of AIDS patients'      immune system

By David Brinn   

A research team at the Hadassah University’s Medical Center in Israel has developed a vaccine that significantly strengthens the body's immune system against the autoimmune aftereffects of HIV infection, a breakthrough that could dramatically make an impact in the treatment of AIDS patients.

Close to a million cases of AIDS have been diagnosed in the US since the beginning of the epidemic, with the HIV/AIDS virus claiming over 20 million lives. Another 39 million people are currently estimated to be living with HIV/AIDS worldwide.

The researchers found that although treatment with the widespread AIDS cocktail of medications kills the virus, the immune system continues to kill healthy cells; this research focuses on developing a vaccine that would arrest this autoimmune destructive process. The results of this study were published in the latest issue of the prestigious Journal of Clinical Virology.

“The HIV virus starts killing white blood cells in the body," lead researcher Dr. Rivka Abulafia-Lapid tells ISRAEL21c. “The AIDS cocktail has been proven to be effective at fighting and treating the virus, but we realized three or four years after patients received the cocktail that their immune system does not always recover. We investigated what was behind this, and found that there's an autoimmune process that continues unabated despite the fact that the patient is taking the cocktail."

New drugs called protease inhibitors, which first approved in 1995, revolutionized the treatment of patients infected with the AIDS virus. These drugs usually are taken with two other drugs called reverse transcriptase inhibitors. The combined drug "cocktail" - also known as highly active antiretroviral therapy (HAART)- has helped change AIDS in the last few years from being an automatic death sentence to what is now often a chronic, but manageable, disease. However, while the virus disappears in many patients, their immune system remains dangerously ineffective against foreign elements, and many of the patients end up dying due to related complications.

“In about 50% of the cases, despite the disappearance of the virus, or at least the virus being below detection level, the immune system does not bounce back," says Abulafia-Lapid.

HIV infects a type of white blood cell called CD4, an integral component in the body's immune system. As HIV attacks and destroys CD4 cells, the weakened immune system becomes less able to fight infection and disease. HIV can also cause AIDS, the last and most severe stage of HIV infection.

Abulafia-Lapid was assisted by Yael Keren-Zur, at the Human Biology Research Center directed by Prof. Henri Atlan. The study was conducted in collaboration with Prof. Zvi Bentwich, and Prof. Irun Cohen from the Weizmann Institute of Science.

The research was based on a suggestion made by Atlan some ten years ago. This was based on the hypothesis that in addition to HIV causing AIDS by invading and killing CD4 blood cells, HIV causes the body's central immune system to start killing these cells independently of the virus as a consequence of an autoimmune process.

Seven patients participated in the study; five of the seven patients responded positively to the vaccine developed by the research team. For most AIDS patients, the central immune system does not recover even if the HIV virus is almost eliminated through treatment with the cocktail of medications. The Hadassah vaccine was designed to stop the continuation of the autoimmune process.

Initially, the researchers identified CD8 cells which are involved in the autoimmune process and are supposedly responsible for destroying CD4 cells in the immune system. In the laboratory, the scientists isolated the CD8 cells from a sample of the patient's white blood cells and mixed them with CD4 cells, and showed that these CD8 cells were involved in the killing process. At this stage, preparation of the vaccine involved neutralization of these CD8 cells and preparation of portions of ten million cells each to be used by injection under the skin in order to trigger a vaccination against these harmful cells.

"We were able to locate the white blood cells responsible - which were programmed to kill the good cells in the body and we were able to isolate them in clinical trials," says Abulafia-Lapid. "We cultured them in a lab setting, and saw that they only grew destructive cells. We killed them, injected the dead destructive cells within the form of a vaccine. This teaches the body to see these cells as foreign and they start fighting them and destroying them."

Seven patients were treated with the new therapeutic vaccine. Each received between three and four injections in a six-month period. Following treatment, the patients CD4 cell count was continually monitored for another two years from their initial vaccination to determine if the number of CD4 cells increased in the peripheral blood, and subsequently, reinforced the strength of the immune system. In five of the seven vaccinated patients, the CD4 cells increased by more than 50 percent.

"After two years of treatment, we found that the cells had been eliminated or were very low. After three injections of the vaccine, five of the seven patients tested showed an increase in healthy white blood cells, which brought them to a certain level considered good for AIDS patients," says Abulafia-Lapid.

"Our aim was not to prevent infection by the virus but to strengthen the immune system and use our vaccination treatment as a complement to the antiviral medication (HAART)", says Abulafia-Lapid. "Since the autoimmune process continues even after elimination of the virus, the vaccine that we have developed is directed to stop this destructive process. In other words, our vaccine complements the cocktail of medications, to stop the body from continuing to destroy itself."

The researchers are continuing to develop the vaccine funded by a grant from Hadasit, the Hadassah subsidiary that promotes and commercializes the intellectual properties generated at Hadassah and by the Center for the Study of Emerging Diseases.

"Now, we plan to conduct extended clinical trials. We've shown that the vaccine is non-toxic and safe. It's not an easy treatment but we've shown that patients benefit from it," says Abulafia-Lapid. "What I envision is making the disease like a chronic infection - the cocktail treats the virus and we help the immune system to recover and allow the patient to continue his life and have his immune system fight any new invaders."