A Canadian university is collaborating with the world’s biggest software company to apply the same method used to manage computer databases, compress digital files and filter e-mail to create HIV vaccine models.
This method has never been used in this area before and there is no guarantee
it will actually work. But, if successful, researchers, scientists and doctors at the University of Toronto, the University of Washington, the Royal Perth Hospital and Microsoft Research believe software algorithms could be used to develop vaccines for other mutating viruses such as Hepatitis C – and even predict the evolution of new viruses.
Acquired Immune Deficiency Syndrome (AIDS) has already claimed the lives of 30 million people around the world, according to the World Health Organization. Nearly 40 million people are infected with HIV, the virus that causes AIDS, and five million people are infected every year.
Drug treatments can be effective, but they’re too expensive for most patients in third-world countries. The problem with HIV, which attacks the body by replicating inside immune cells, is that it’s able to mutate – in fact, every person infected with the virus carries a different strain. At the Royal Perth Hospital in Australia, for example, tests on 473 HIV patients found 473 different strains of the virus. This has made development of a vaccine extremely difficult.
Typical vaccines are near-copies of the virus that is being vaccinated against; they essentially simulate an infection. This doesn’t work with HIV, said Nebojsa Jojic, a researcher with Microsoft Research in Redmond, Wash.
HIV mutates at a high rate – or at the “brink of chaos” – which allows it to produce myriad strains. If you immunize against one strain, he said, it will change itself enough so it can still function within that patient.
“HIV has to evolve to avoid being recognized,” he said.
However, there is still some repetition among these different strains. Most types of information contain simple or complex patterns that repeat with minor alternations, and computers can help find those patterns automatically. In this case, the goal is to construct a sequence of amino acids that includes patterns that stimulate the immune response to HIV.
In other words, researchers are looking for patterns in the way the HIV virus mutates.
“The sheer amount of data generated is too large to be handled in any way other than computationally,” said Vladimir Jojic, a researcher at the University of Toronto involved with developing algorithms for vaccine design (and the brother of Nebojsa at Microsoft Research). The University of Toronto is also taking a lead in merging the areas of biology and computational sciences, he said.
But the two approaches of computational studies and specific experiments carried out in a laboratory are actually quite complementary, he added. To come up with a vaccine design, for example, you need HIV sequences. And to verify immune response to the vaccine, you need to go back to the lab and check whether there is a response. “So you definitely need to go back and forth between two methods,” Vladimir said.
But it’s difficult to say if these algorithms are speeding up the vaccine discovery, he said. The aim, rather, is to help biologists discover near-optimal vaccines given current understanding and knowledge of the immune system.
U.S. Food and Drug Administration (FSA) trials can take several years – and we’re not at that stage yet. “We are still pursuing smaller scale experiments that would mimic the FDA trials,” Vladimir said, “but with the goal of gaining more information that would help us both validate and improve the vaccine.”
Researchers at the Royal Perth Hospital are attempting to locate genetic patterns in the way HIV mutates, and researchers at the University of Washington are tracing the genetic family tree back to the earliest strains of the virus.
Biology is becoming a data-driven discipline, requiring much more sophisticated computer science. And in the case of HIV research, the usual scientific approach doesn’t work very well, Nebojsa said.
But even with the help of computers, a cure isn’t exactly around the corner: we’re at least five to 10 years away from a working vaccine, Nebojsa added.