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DoD, NIH Back Pitt Alphavirus Vaccine Research

William Klimstra, Ph.D., is associate professor at the University of Pittsburgh Center for Vaccine Research. Image credit: Emily O'Donnell/Pitt

Scientists at the University of Pittsburgh Center for Vaccine Research (CVR) recently received nearly $4 million through five federal grants to study a group of related mosquito-borne viruses. The ultimate goal is to develop vaccines and therapies against the deadly diseases.

The research will be conducted in the Regional Biocontainment Laboratory (RBL) at Pitt, a unique, high-security facility that allows scientists to safely contain and examine potentially dangerous pathogens.

William Klimstra Pitt Vaccine Research
William Klimstra, Ph.D., is associate professor at the University of Pittsburgh Center for Vaccine Research. Image credit: Emily O’Donnell/Pitt

“This recent funding highlights the globally significant research being done right here in Pittsburgh to help develop ways to protect people against emerging diseases of growing concern,” said Ronald Montelaro, Ph.D., professor and co-director of Pitt’s CVR.

William Klimstra, Ph.D., associate professor at Pitt’s CVR, is principal investigator on three of the grants and about half the funding. Kate D. Ryman, Ph.D., also associate professor at Pitt’s CVR, is principal investigator on the other two grants.

“While the number of people who get these diseases is relatively small, the severity of disease and their potential emergence in larger populations or for use as bioweapons drive the necessity for development of countermeasures,” said Dr. Klimstra.

Two of Dr. Klimstra’s grants, both from the National Institutes of Health and totaling $847,000, focus on eastern equine encephalitis virus (EEEV), a rare disease that is found primarily in the Atlantic and Gulf states and kills about half of the people it infects. One of the grants will be used to examine a specific part of the genetic code of the virus that is largely responsible for the severity of human disease, while the other will go toward developing a novel, live-attenuated vaccine against the virus.

His other grant, which is a collaboration with colleagues at Washington University in St. Louis and Oregon Health and Sciences University, will provide $1.2 million to Dr. Klimstra and CVR colleagues from the U.S. Department of Defense (DOD). This will be used to develop a novel, inactivated vaccine against three strains of alphavirus, a group which comprises about 30 different viruses mainly transmitted by mosquitoes – including EEEV and Venezuelan (VEEV) and western (WEEV) equine encephalitis viruses, which cause periodic outbreaks in the Americas.

Dr. Ryman received $1 million from the DOD to study how these three encephalitic alphaviruses and another mosquito-borne virus, Rift Valley Fever virus (RVFV), enter the brain. The RVFV component is led by Amy Hartman, Ph.D., assistant professor at Pitt’s CVR.

The goal is to develop ways to limit brain entry by the virus and identify biological markers of disease severity to use as a measure of the effects of the vaccines and therapeutics. This grant also involves studies with collaborators at the University of Wisconsin.

Finally, Dr. Ryman received $725,000 from the DOD in collaboration with investigators at the Naval Medical Research Center to raise anti-VEEV antibodies by immunizing cows that have been genetically altered to produce human antibodies. These antibodies will then be assessed for their potential use in protection against alphavirus diseases, similar to convalescent sera, which is derived from the blood of people whose immune systems successfully fought off an infection.

Several of the grants have option periods that, given successful results in initial studies, will add an additional $3 million in funding.

“The technologies used in these studies and the systematic manner in which vaccines and therapeutics for the alphaviruses are being developed are novel and, given positive results, these approaches can be readily applied to other emerging infectious diseases,” said Dr. Ryman.

Some of the studies also involve Simon Watkins, Ph.D., of Pitt’s Center for Biological Imaging, and Douglas Reed, Ph.D., aerosol director for Pitt’s RBL.

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