Putting Immunity in a Test Tube

You've heard of artificial limbs and artificial hearts but what about artificial immune systems? Add another notch to the test tube: scientists at VaxDesign, a five-year-old biotechnology company based in Orlando, Florida, have created a simulated human immune system, called the Modular Immune In Vitro Construct (MIMIC for short). The dime-sized immune system can predict how humans will respond to new vaccines. The goal? To streamline vaccine research and hasten the eradication of global killers, such as AIDS.

Here's how MIMIC works: Donors fork over a few white blood cells — specifically, peripheral blood mononuclear cells, or PBMCs, which include infection-fighting lymphocytes like T and B cells. The blood cells go into specially designed "tissue constructs," which are forged from collagen and endothelial cells and designed to act just like human skin (think a Barbie Dream House for white blood cells). Each construct is hunkered inside an individual well where the blood cells mingle with the faux tissue. As the blood cells get cozy, they flourish, and a teensy, homegrown, fully functioning human immune system is born. Up to 96 wells, enough for 96 individual immune systems, fit on a plate roughly the size of a deck of cards. From here, the next step is to toss a vaccine into the mix and watch the action unfold. (MIMIC uses skin-like constructs, since cuts and open sores on the skin are a natural entry point for many viruses, but different viruses prefer different doorways, so VaxDesign has already created a lung construct, and artificial nasal and intestinal linings are in the works.)

Traditionally, new vaccines are tested in mice, rabbits or, in the case of AIDS, monkeys. But animal testing is time-consuming, expensive, and controversial. The biggest bugaboo of all is translation. No matter how well an experimental vaccine works in animals, the leap to humans is riddled with uncertainty and unforeseeable complications. Last year's collapse of a late-stage AIDS vaccine trial involving thousands of volunteers is a case in point. The experimental vaccine used in the STEP study, co-sponsored by the National Institutes of Health and the vaccine's creator, pharmaceutical giant Merck, looked promising in monkeys but failed miserably in human trials when it appeared to increase the rate of HIV transmission in study participants. "In the end," says Wayne Koff, senior vice president of research and development at the International AIDS Vaccine Initiative (IAVI), "you can only extrapolate so much from a monkey model."

VaxDesign's model may soften, if not sidestep, such devastating setbacks by allowing researchers to road test a vaccine in human immune systems earlier than ever before. In essence, the constructs act as "clinical trials in a test tube." When an experimental vaccine enters the tissue constructs, the simulated immune system will sound the alarm, just as it would inside a human. Then, it does what an immune system does best — whips up antibodies. If the vaccine is successful, the antibodies will wipe out the targeted disease the next time it shows up. Best yet, researchers can test hundreds of different donors from a diverse genetic pool, a feat that's impossible to replicate with lab animals since they are bred to be genetically similar. "The information you get from this type of test is far and beyond what you'd get out of a mouse study," says Michael Rivard, vice president of corporate development at VaxDesign, "both because it's humans and because you can see the effect across a spectrum of genotypes."

MIMIC's speed and flexibility makes it particularly attractive to AIDS vaccine researchers. As things stand, it takes months for potential AIDS vaccines to graduate from small-animal trials to monkey studies. "That takes a lot of time, and, with HIV, we don't have a lot of time," says Koff. "We asked the question is there a way to do it faster and take it to humans more quickly?"

IAVI's search for an answer led them to Florida. Earlier this month, IAVI chose VaxDesign to receive the first award from its Innovation Fund, which supports potential breakthrough technologies applicable to AIDS vaccine research. Compared to what's available, MIMIC offers a dramatic increase in scale and speed, says Koff. "What's more, by collecting immune cells from different donors, promising vaccine candidates can be tested in diverse populations before they enter humans."

If all goes well with test runs on licensed vaccines for yellow fever and rabies, VaxDesign will begin work on potential AIDS vaccines next year. While critics might argue that MIMIC is too oversimplified to be useful, Koff doesn't agree. "From our point of view, [VaxDesign is] further advanced than anyone in the field in terms of tissue engineering and vaccine design," he says. "If they are successful it will revolutionize all of vaccinology."

And the possibilities for medical breakthroughs don't end at vaccines. VaxDesign hopes to use the MIMIC system to study autoimmune diseases, like multiple sclerosis and rheumatoid arthritis, as well as inflammatory conditions, such as Crohns disease. The aim is to better understand both how these diseases impact immune function as well as help design smarter drugs. Says Koff, "the opportunities are endless."