Researchers Turn to Mathematical Tool to Find an HIV Vaccine Target

A strategy in the development of an HIV vaccine relies on a mathematical technique historically used to predict changes in the stock market.

Developing an HIV vaccine is a fairly daunting task, considering the nature of the virus: it is able to mutate so frequently that researchers have a difficult time trying to establish a vaccine target.

Researchers from the Massachusetts Institute of Technology (MIT) and the Ragon Institute, both in Cambridge, Massachusetts, have adopted a new strategy in their search for a vaccine target—using probability theory and mathematical physics to pinpoint and analyze HIV mutations. The researchers, led by Arup Chakraborty of MIT and Bruce Walker of the Ragon institute, presented their findings at the Biophysical Society 56th Annual Meeting on February 25-29, 2012 in San Diego, California.

Rather than examining single amino acids for clues, the researchers focused on groups of amino acids which mutate in tandem in order to ensure viability of the virus. In particular, they studied mutations of groups that make the virus more susceptible to self-destruction when occurring in combination together. The co-evolving groups of amino acids that the investigators set out to identify were ones that had a “high number of negative correlations (meaning multiple mutations would destroy the virus) and a low number of positive correlations (meaning the virus could survive multiple mutations).”

Using the random matrix theory, which is also used to measure fluctuations in the stock market, researchers discovered that the amino acid groups that met their criteria were in a region called Gag sector 3. This area of DNA is involved in maintaining the protein capsid, which houses viral RNA material. The investigators also noted that this sequence in the DNA was also responsible for helping HIV-infected individuals naturally fend off attacks; their immune systems were found to “preferentially target Gag sector 3 over other proteins.”

The team of researchers is currently working on ways to direct the immune system to selectively target Gag sector 3 proteins, and they expect to begin testing in animal models soon.