International Struggle to Develop HIV/AIDS Vaccine Continues

By Cheryl Pellerin

The 20-year effort to develop a vaccine that protects against the AIDS-causing human immunodeficiency virus (HIV) meets more challenges as clinical trials are discontinued and the National Institute of Allergy and Infectious Diseases (NIAID) rethinks its approach to HIV vaccine design and development.

NIAID, part of the National Institutes of Health (NIH), announced in September 2007 that it would discontinue two HIV vaccine clinical trials. On July 17, it announced it will not move forward with a vaccine clinical trial called PAVE 100 that would have enrolled 8,500 volunteers in the United States, South America, the Caribbean and eastern and southern Africa.

"If there is one area of the science of HIV that is still quite problematic, that has to do with vaccines," NIAID Director Anthony Fauci said during a July 15 briefing. "Why? We have a lot of money, we have a lot of brilliant people thinking about it, why is it so difficult? The reason is that HIV is different - namely, the natural [human] immune response to HIV is inadequate."

By the end of 2007, according to the World Health Organization, an estimated 33.2 million people around the globe were living with HIV and 2.1 million of these were children. An estimated 2.5 million people were newly infected in 2007 and 2.1 million died from AIDS. About two-thirds of all people with HIV live in sub-Saharan Africa.

FAILED TRIALS

One of the discontinued studies was a large, international HIV vaccine clinical trial called the STEP study. Beginning in 2004 it enrolled 3,000 noninfected volunteers in Australia, Brazil, Canada, the Dominican Republic, Haiti, Jamaica, Peru, Puerto Rico and the United States.

The study was co-sponsored by NIAID and the pharmaceutical company Merck & Co., Inc., which developed and supplied a candidate vaccine designed to stimulate production of immune system T-cells that can kill HIV-infected cells. The goal was to determine if the vaccine could prevent HIV infection or reduce the amount of HIV in the blood, or both.

"If you inject a nonhuman primate with a vaccine that induces a T-cell response," Fauci said, "you don't protect them against infection but you blunt the original viral burst and make the set point [the relatively steady viral load during the asymptomatic period of HIV infection] low so two things are possible. One, the animal will go a longer period of time without requiring therapy. Two, the animal will be very unlikely to be infective [to others] because its viral load is low."

With that as a principle, he added, the STEP study was developed.

In 2007, an independent data and safety monitoring board concluded the STEP study vaccine did not prevent HIV infection or affect the course of the disease in those who became infected with HIV. Some of the volunteers, in a still-unexplained paradoxical effect, Fauci said, "actually had a greater risk of getting HIV infected if they were naturally exposed to HIV."

The same vaccine was being tested in South Africa by the NIAID-funded HIV Vaccine Trials Network and the South African AIDS Vaccine Initiative in a separate NIAID-sponsored clinical trial called the Phambili study. Immunizations of 799 volunteers in that study were suspended.

The PAVE 100 trial was to begin U.S. recruitment in October 2007 but was postponed following the decision to halt immunizations in the STEP study.

NEW APPROACH

To accelerate the translation of basic discoveries about HIV into advances in vaccine design and evaluation, NIAID in June formed the Vaccine Discovery Branch in the Division of AIDS Vaccine Research.

"There is broad scientific consensus that designing a safe and effective vaccine to prevent HIV infection will require enormous advances beyond present-day knowledge," Fauci said in a statement.

The new branch will monitor scientific developments in multiple fields related to HIV vaccine discovery, building more bridges between basic researchers and HIV vaccine designers, identifying gaps in knowledge about developing a preventive HIV vaccine and promoting research to fill the gaps.

The Vaccine Discovery Branch will have oversight of the Center for HIV/AIDS Vaccine Immunology, a consortium of universities and academic medical centers that NIAID established to solve major problems in HIV vaccine development and design.

"A vaccine for HIV is not going to be like a vaccine for any other infection," Fauci said. The fundamental principle of vaccine development, he added, is to mimic what the natural infection does in the body.

"If you look at all the big killers - smallpox, measles, polio - although a certain percentage of people get sick and a smaller percentage die, at the end of the day most people recover spontaneously from these terrible diseases," Fauci said. "They do so because their body generates an immune response that ultimately clears the virus or microbe from the body and then it protects you against any subsequent challenge. Once you've had smallpox, that's it. If you've survived it, you're never going to get smallpox again."

That will not be the case with HIV, he said.

"It is extremely unlikely that we will have a completely detective vaccine against HIV. What we're going to have to do is use HIV vaccine as a very important tool in the toolkit of HIV prevention. You won't be able to say, 'Now I'm vaccinated so I have no risk.' But hopefully it will be a powerful enough tool that it will turn the tide on the rate of infection."

More information about HIV/AIDS ( http://www.aidsinfo.nih.gov/ ) is available on the NIH Web site.

Source: U.S. Department of State

judythpiazza@newsblaze.com