Three of the top-10 causes of death worldwide are infectious diseases, with billions of people harboring potentially lethal pathogens such as the hepatitis B virus, malaria, tuberculosis, the influenza virus and HIV. Taking a creative approach to address this problem, Penn Medicine and colleagues at Oxford University and Massachusetts General Hospital have received an additional five-year round of funding totaling $10 million from the National Institutes of Health (NIH) to explore using a promising cancer treatment to combat these dangerous viruses.

E. John Wherry, the chair of pharmacology at the Perelman School of Medicine of the University of Pennsylvania, will lead the Penn team in the collaboration to study the impact of an immunotherapy called PD-1 blockade on viral immunity in humans. This grant renewal is part of the NIH’s Cooperative Centers for Human Immunology consortium.

The programmed cell death protein 1 (PD-1) is located on an immune cell’s surface and plays a key role in restraining T cell activity. While this control of immune response can prevent autoimmune diseases, it can also block the immune system’s ability to kill cancer cells. PD-1 inhibitors can thwart PD-1, ramping up the immune system’s capacity to attack tumors.

“These medications have also shown early promise against infectious diseases,” said Dr. Wherry. “But there is almost no information in humans about how targeting PD-1 affects immunity to viruses and vaccines.”

The new grant aims to address this crucial gap in knowledge to improve prevention and treatment of infectious diseases. The primary goal is to apply PD-1 blockade in hepatitis B virus infection and flu vaccination, identifying innate and adaptive immune effects controlled by PD-1 signals in response to viruses and vaccines in people.

By studying humans, the new grant will seek to address a common challenge in basic biomedicine: Much research now only takes place in mice, making the translation of insights gained from animal studies to humans limited.  “Flu and other respiratory infections alone kill up to half a million people globally each year,” said Dr. Wherry. “Vaccines remain only partially effective, especially in the most vulnerable populations. Although we have learned a great deal about human immunology in the past several decades, we still have a long way to go.”