HIV Vaccines to be Tested at the Disease's Epicenter

An international research consortium plans to begin testing four new HIV vaccines in 2014 in a province of South Africa where the infection rate is among the highest in the world.

The unusual effort to test several vaccines nearly simultaneously reflects the difficulty of finding a way to prevent HIV infection, says Bruce Walker, a Harvard Medical Scho­­ol professor and one of the founding scientists of a new research center opening this month in Durban, in KwaZulu-Natal province, where the tests will occur.

More than a fifth of KwaZulu-Natal’s adult population carries HIV, and basing the vaccine effort there “allows us to very efficiently do vaccine trials and very efficiently get answers,” says Walker. Because the infection rate is so high, it could take as little as two years to determine if a given vaccine works.

Walker estimates that only 2,000 patients will need to receive each vaccine to discover whether it offers protection against the virus. “The same study in Thailand might take 16,000 patients, because the incidence is so much smaller,” says Walker. “You figure you need about 90 to 100 infections in your cohort to see if there’s an impact.”

There have been three large tests of HIV vaccines so far, but none succeeded in protecting people from becoming infected. Major disappointments came in 2003, 2007, and 2009, when a vaccine manufactured by drug firm Sanofi showed inconclusive results in a study involving 16,000 volunteers.

“We as a field have only ever actually tested three different concepts [for vaccines], and each time we’ve sort of finished one concept and then started another one,” says Walker. “Our plan is to take things forward in parallel and not in sequence.”

Vaccination typically works by inoculating people with dead or attenuated forms of a virus, or with specific molecules present on the virus’s surface. That teaches the immune system to recognize and attack the microörganism. Developing a vaccine against HIV, a retrovirus, has proved difficult because it can mutate quickly and evade the protective effects of a vaccine.

Of the four new vaccines Walker says will enter testing, one is a canarypox virus engineered to express two surface proteins of HIV, which were chosen based on computational studies of the virus’s weaknesses. Another is a protein that’s been twisted to mimic HIV’s shape. The most unusual of the new candidates is a synthetic vaccine made from fatty nanoparticles packed with genetic material. Walker believes a synthetic vaccine could get regulatory approval more quickly than others, and might be easier to alter if the initial results are disappointing.

In developed nations, HIV infection has become a largely treatable condition because of anti-retroviral drugs, which can suppress the virus and prevent AIDS. In Africa, however, those medications have proved too expensive and difficult to use widely.

“I don’t think we can treat our way out of this epidemic” with drugs, warns Walker, who is also director of the Ragon Institute, a vaccine research center in Boston that has received more than $100 million in grants and donations (see “Three New Initiatives”) and now effectively directs HIV vaccine tests globally.

According to the United Nations’ UNAIDS program, over 30 million people worldwide carry HIV, and a million die from it each year, mostly in places like South Africa, which has more than 17 percent of the world’s HIV cases. Walker says the size of the epidemic in South Africa alone is reason enough to spend $100 million on a vaccine. “The damage to society in general from a disease like this, that hits people in the prime of their lives, is just enormous,” he says. “A mother dies and a child is orphaned. These problems just continue to swell.”