New Hope in Quest for AIDS Vaccine

How a new scientific breakthrough could finally lead to a cure

Published on October 26, 2012by Elaine Meyer

It is hard to believe now that in 1984, U.S. Health and Human Services Secretary Margaret Heckler said at a press conference that an AIDS vaccine would be ready for testing within two years.

Twenty-eight years later, a vaccine still is not a reality. But good news came this week when a consortium of researchers led by the Center For the Aids Programme of Research in South Africa (CAPRISA) announced the discovery of a way in which the human body can kill most types of HIV, an important and possibly decisive advance in the quest for a vaccine.

Vaccines are created by mimicking antibodies, which are produced by the body’s immune response to fight viruses. But HIV manages to evade this response because of the high genetic diversity of the virus and its ability to evolve rapidly—sometimes as much as every day in a single patient—so antibodies cannot target it.

However three years ago, scientists discovered that some HIV infected people produce “broadly neutralizing antibodies” that are able to fight against most strains. Rare at first, broadly neutralizing antibodies are today believed to exist in one-fifth of infected people.

The problem is scientists did not know until now how the body produced these antibodies, making it impossible to create a vaccine that could replicate this response.

The researchers discovered unique changes in the virus of two women which enabled them to produce broadly neutralizing antibodies that killed up to 88 percent of HIV types. One of the two women had been enrolled in a large clinical trial by CAPRISA of an antiretroviral vaginal gel that appears to significantly reduce rates of HIV acquisition.

In follow-up studies of the two women, consortium researchers Dr. Penny Moore and Professor Lynn Morris of the National Institute for Communicable Diseases in Johannesburg traced the evolution of the virus to understand how these women were able to produce the powerful antibodies.

They found that the women’s initial infecting strain of HIV did not have an antibody target on its outer covering. However, over time the body’s immune reaction pressured the virus to cover itself with a sugar called glycan which opened up a vulnerability on the virus that the broadly neutralizing antibodies could target.

It is an “elaborate game of ‘cat and mouse’ between HIV and the immune response of the infected person,” says Dr. Moore.

“Now that we know one way to get the body to make broadly neutralizing antibodies, we need to figure out how to make an AIDS vaccine that mimics this,” says Dr. Salim Abdool Karim, director of CAPRISA and a professor of clinical epidemiology at Columbia University’s Mailman School of Public Health.

The nearly 30-year search for an AIDS vaccine faced a stunning setback in 2008 when two trials of a promising vaccine from Merck not only failed to protect people from the virus but actually put them at increased risk of infection.

As a result there has been much debate in the field on whether it is worth investing significant resources in the development of a vaccine, especially as studies in recent years have shown that another tool, powerful antiretroviral drugs, can control the virus for many years and prevent transmission to people who are not infected.

“[The 2008 trial] had an extremely chilling effect on the whole field,” said Colonel Nelson Michael, director of the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research, according to Reuters.

In the last year however, because of the discovery and increased presence of broadly neutralizing antibodies, hopes for a vaccine have been reinvigorated, which is why this week’s advance is so significant.

Although the breakthrough received some coverage from the American media, it was all over website homepages and newspaper front pages in South Africa, where infection rates are still high, and—despite the advances in antiretrovirals—a vaccine is the surest hope of ending the pandemic.

While it is a significant advance, there is “lots of work still to do,” says Dr. Abdool Karim. Scientists still have to create a vaccine that could mimic the response that creates the potent antibodies and test it in clinical trials, which often take several years.

“Of the 34 million people living with HIV globally, two-thirds are in sub-Saharan Africa,” Dr. Abdool Karim  told South Africa’s Gant Daily this week. “It’s unlikely that we’ll be able to eradicate this epidemic without a vaccine.”