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University of Houston wins NIH grant for vaccine study

It is spread to humans by mosquito bites, causing arthritic symptoms so severe that some victims can't even walk. While rarely fatal, the effects of the chikungunya virus can last up to a year.

More than two million people have contracted the chikungunya virus in the past five years. Most of the infections have occurred in Southeast Asia, but infectious disease experts consider its spread to the United States likely because of global travel.

With no vaccine available for this debilitating virus, federal health and security officials have targeted it as a possible bioterrorism agent.

Groups around the world are working to develop a vaccine, including a regional team that involves Navin Varadarajan, a University of Houston engineering professor who is working on developing a new method of testing potential vaccines for the chikungunya virus.

Varadarajan, an assistant professor of chemical and biomolecular engineering at UH, received a two-year, $361,000 grant administered by the Western Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research and funded by the National Institutes of Health. He is partnering with researchers at the University of Texas Medical Branch at Galveston and Tulane University.

"What we are looking to study and characterize is a vaccine-induced immunity," Varadarajan said. "If I have a tube of blood from a vaccinated subject, how do we determine the effectiveness of the vaccine?" Like many vaccines, the ones being developed by the UTMB-Tulane group attack chikungunya in several ways.

Varadarajan is testing the ability of potential vaccines to spur the immune system to attack human cells that essentially have been taken over by the virus and become reservoirs for it to multiply.

When this occurs, the immune system produces CD8 T-cells that kill the co-opted cells. However, each CD8 T-cell is programmed to fight one particular disease. Ideally, the vaccines being tested will spur the immune system to produce CD8 T-cells that recognize only chikungunya-infected human cells.

But isolating and studying CD8 T-cells can be extremely challenging through standard research techniques. The cells are only 10-20 microns across and less than a quarter the width of a human hair, while the blood samples from subjects injected with the vaccine are placed on much larger plates, which makes it difficult to identify CD8 T-cells that are specific to a certain virus.

Varadarajan is developing a specialized polymer slide called a microwell array. Roughly the size of a standard slide, it consists of about 85,000 individual chambers, each 50 microns by 50 microns, just the right size to isolate and study individual cells.

"If we shrink the container small enough so that its dimensions are similar to those of a single cell, we can achieve almost single-cell resolution. So within the same footprint, we can look at lots of cells," Varadarajan said.

After a blood sample is placed on the microwell, not all the cells isolated in its chambers will be CD8 T-cells programmed to fight chikungunya. To see which ones do, Varadarajan will then introduce cells that have been covered with pieces of the chikungunya virus, spurring the CD8 T-cells that spark chikungunya into action.

Varadarajan will then use a microscope to take images of each chamber and a computer program will analyze these images and identify the CD8 T-cells that are fighting chikungunya. He will next remove those cells from their chambers and clone them by the million, allowing him to study every aspect of the CD8 T-cells that attack chikungunya.

Varadarajan will use that information to evaluate the effectiveness of potential vaccines for chikungunya and provide guidance on vaccine development to his partners.

"Finding a chikungunya vaccine is a priority given the virus' potential to spread quickly and its possible use in bioterrorism," said Varadarajan. "With this research, we can help the vaccine developers identify which potential vaccines are most effective and, hopefully, find a suitable one as quickly as possible."


Contact: Laura Tolley
University of Houston

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