Dartmouth professor works on HIV vaccine

By Tom Owen

Dartmouth professor works on HIV vaccine

A research consortium led by engineering professor Margaret Ackerman has received an $8 million-grant from Partners Health Care, a non-profit health care provider in Massachusetts, to fund the development of a new type of HIV vaccine, according to Ackerman.

The consortium, led by Ackerman and Galit Alter, a professor at Harvard Medical School, includes researchers with a wide variety of specialties from both national and international institutions, Ackerman said. Although researchers have been trying to develop HIV vaccines for three decades, Ackerman’s initiative differs from its predecessors by shifting the focus from the adaptive immune system to the innate immune system, she said. Typically, when the body is infected with a virus, the immune system responds by producing neutralizing antibodies, which block structurally important parts of the pathogen from binding with the body’s cells. This system has been the primary focus of the vast majority of HIV vaccine research efforts, and investigators have for years sought to develop a drug that would induce this response in order to prevent infection. However, one of the factors that contributes to the difficulty of developing an HIV vaccine is the disease’s rapid rate of mutation, according to Ackerman. Because the disease constantly mutates into different strains, an effective vaccine would require very “broad coverage,” which researchers have not been able to produce by focusing on the adaptive immune system.

“There is more viral diversity in a single person infected with HIV than in all of the people in the world infected with the flu,” Ackerman said.

Ackerman said she hypothesizes that the innate immune system — a “beacon for waking up the rest of the immune system” — could be used to neutralize the infection. While the innate immune system is usually considered a temporary defense measure used by the body until the adaptive immune system can identify and destroy the pathogen, Ackerman said a successful HIV vaccine could result from utilizing the innate immune system’s signalling mechanisms.

This hypothesis is supported by the results of a three-year vaccine trial conducted in Thailand, the results of which were published in 2009. Although the study was controversial and researchers are still debating the results, the trial resulted in a statistically effective vaccine, and subjects did not exhibit the typical hallmarks of an adaptive immune system response, according to Ackerman.

“The trial showed success despite the absence of the neutralizing antibodies,” Ackerman said. “Clearly, something else must have been contributing to the success of the vaccine.”

The controversy of the trial stems from the fact that the vaccine — a combination of two unsuccessful HIV vaccines — was found to be only 31 percent effective, a statistic that created doubt about the legitimacy of the results.

With the help of computer science professor Chris Bailey-Kellogg, Ackerman is engineering a platform to assess the many variables involved with developing an effective vaccine.

The team’s efforts are not guaranteed to prove successful, but the results have been promising, according to Eric Brown, a first-year student at Thayer School of Engineering.

“It’s definitely something that needs to be investigated,” Brown said.

The Partners Health Care funding was awarded through a grant from the Collaboration for AIDS Vaccine Discovery, sponsored by the Bill and Melinda Gates Foundation.

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