Stalking an elusive thief

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Researchers advance HIV/AIDS vaccine

By Roger Snodgrass

To catch a thief requires a clever trap.

Nobody knows what it takes to snag the versatile HIV/AIDS virus that has stolen the lives of 25 million people around the world in the last three decades, because it hasn’t been done.

Bette Korber, one of Los Alamos National Laboratory’s best-known researchers, has been stalking HIV for more than 15 years and is about to carry her ideas forward into a human trial.

“It’s been under negotiations for a while and the Gates Foundation and National Institutes of Health are funding it,” she said in a recent interview. “A human vaccine group is making the vaccine now.”

With a team of collaborators at the lab and around the world, she has inventoried the tiniest pieces of the virus, sequenced the genetic structure, mapped a family history and laid out the twisted strands of its success in the world.

While there are some drugs that have been effective in slowing the advance of the disease, there is not yet a vaccine to prevent it.

Since 1997, Korber has been trying to design a vaccine for HIV that could stimulate the human immune system to arm itself against a marauder that is also a master of the quick disguise.

“It’s different in every person and evolves very rapidly,” she said

One of the reasons a preventive solution is so hard to find is because the HIV virus, has extraordinary abilities to mutate. HIV-1, the most common form, mutates quickly to evade drug resistance. Any preventive approach to controlling it will have to arm the potential host with extraordinary responses.

Recently, Korber, working with two teams of researchers, including LANL coworkers Will Fischer, Sydeaka Watson and James Szinger, published two technical papers extending a strategy that she has been working on all along, to find the formula for a vaccination that can outmaneuver the wily virus and prevent infection.

“We figured out a way to maximize the number of immunologically relevant variants you can put into it,” Korber said.

A laboratory announcement explained the strategy as one that develops “mosaic vaccines,” that provide coverage for a range of forms rather than each individual manifestation of the virus.

Korber explained that these sets of molecules intended to stimulate defensive antibodies were cooked up on the computer using a code written by Will Perkins.

Perkins program synthesized a routine that could encode them, so they could be incorporated in the test vaccine.

A simple model was tested first in mice, she said, and they responded well, so the next round tested macaques, which are primates like humans and a species of monkey.

“Each of these steps takes two years,” Korber said.

The most recent test by an experimental vaccinologist and physicians used rhesus monkeys. In the next step, Korber said, “We’ll be helping with the analysis and results.”

In October 2009, the laboratory announced that Korber and collaborators were using the lab’s Roadrunner supercomputer to create the world’s largest evolutionary tree for HIV.

The mapping project for the International Center for HIV/AIDs Vaccine Immunology (CHAVI) consortium created a family tree from more than 10,000 sequences gathered from more than

400 individuals infected with HIV.

The purpose of the study, Korber said at the time, was to identify common features of the transmitted virus to create a vaccine that could recognize the virus before the body’s immune system causes it to react and mutate.

The mosaic strategy was found to be successful in the most recent tests using Rhesus monkeys and was credited with a four-fold improvement in the monkeys’ immune response to HIV-1, compared to natural vaccines like those used in the past.

“The next step is to see whether the improved immune response found in Rhesus monkeys will hold up in humans, so small-scale human safety and immune response studies are being launched at Harvard and at Duke to explore the possibility,” Korber said.