AIDS vaccine gets closer, but still may be a decade away

From the San Jose Mercury News:

Hours after HIV researchers announced the achievement of a milestone that had eluded them for a quarter of a century, reality began to set in: Tangible progress could take another decade.

A Thai and American team announced Sept. 24 in Bangkok that they had found a combination of vaccines providing modest protection against infection with the virus that causes AIDS, unleashing excitement worldwide. The idea of a vaccine to prevent infection with the human immunodeficiency virus, HIV, had long been frustrating and fruitless.

But by Sept. 25, initial euphoria gave way to a more sober assessment. There is still a very long way to go before reaching the goal of producing a vaccine that reliably shields people from HIV.

Some researchers questioned whether the apparent 31 percent reduction in infections was a statistical anomaly resulting from the small number of HIV cases observed in the trial.

If the protection was real, how did the vaccine do it? Researchers have never observed antibodies or other blood molecules that could block HIV infection.

Experts predicted it will take two to three years to identify the biological molecules linked to the protection, and another five to 10 to produce a vaccine to test in people.

Despite the many questions, researchers are ecstatic. After 26 years, they have finally made progress on demonstrating the feasibility of an HIV vaccine, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, which largely funded the $120 million study. But "is it a vaccine that is ready for prime time? No."

The trial, which began in 2003, had been disparaged by many as a waste of time because the two vaccines used in it had been shown in individual trials to produce no benefit. But some researchers speculated that using them together, with one priming the immune system and the second boosting the response, might work better.

The primer is Alvac, by Sanofi Pasteur, which uses a defanged canarypox virus to carry three synthetic HIV genes into the body. The boost is from Aidsvax, made by VaxGen, a South San Francisco biotech company, and now owned by the nonprofit Global Solutions for Infectious Diseases. It contains a genetically engineered version of an HIV surface protein.

The study was of more than 16,000 volunteers in Thailand, all from the general population, not high-risk homosexuals and intravenous drug users used in past studies. Half received four priming doses of Alvac and two boosts of Aidsvax over six months; half received placebos.

After three years, new HIV infections were seen in 74 of the 8,198 people who received the placebo, but in only 51 of the 8,197 given the vaccine, a statistically significant 31 percent reduction.

Full details will be released next month at a Paris conference. Dr. Salim S. Abdool Karim, an epidemiologist at Columbia University and director of the Centre for the AIDS Programme of Research in South Africa in Durban, said he was eager to know if people who were vaccinated and stayed healthy had a bigger response from blood cells called cellular T lymphocytes.

And if not, then "what kind of compounds were the cells making when you inoculate them with the vaccine?" asked Dr. Spoyros Kalams, director of the HIV Vaccine Trials Program at Vanderbilt University.

Researchers will begin to sift through the blood of those who were vaccinated and resisted infection and those who did not, seeking molecules more abundant in the healthy people, Fauci said.

Then, they can look for ways to make a more effective vaccine.