New infectious diseases are on the rise: In 2015 and 2016, there was an upswing in Zika outbreaks in the U.S., and the virus still impacts many parts of the world. The Ebola epidemic in the Democratic Republic of Congo (DRC) is the second largest in history, according to the CDC. HIV remains an incurable disease.
All of these epidemics beg one question that members of Wistar’s Vaccine & Immunotherapy Center are interested in solving: can we create a cure for infectious diseases?
In particular, Kar Muthumani, Ph.D., assistant professor in Wistar’s Vaccine & Immunotherapy Center and director of the Laboratory of Emerging Infectious Diseases, is pursuing whether we can develop antibody therapeutics to help people recover from infection.
“Historically, vaccines have been our answer to global disease prevention but look at Ebola in the DRC — when an outbreak has already started, people with the disease need a therapeutic not a preventative answer,” said Muthumani. “In my lab at Wistar we are focused on therapeutics that could be given to anyone who comes down with symptoms; patients would receive a blood test to confirm the type of disease and take the therapy for that specific disease.”
Muthumani’s expertise is in design and creation of synthetic DNA-based vaccines and therapeutics. His work crosses over between infectious diseases and cancers. He’s actively working on Zika virus, Mayaro virus, chikungunya, Middle East respiratory syndrome (MERS), Nipah virus, Junín virus (JUNV), Crimean-Congo hemorrhagic fever (CCHF), dengue virus, and HIV.
Muthumani is strongly committed to antibody therapy as a strategy to provide relief for emerging disease situations. Antibody therapy is a form of immunotherapy that uses monoclonal antibodies (mAb) to bind to specific cells or proteins that will prevent infection and/or stimulate an individual’s immune system to attack the harmful cells. He is currently working with partners to characterize immune cells and antibodies from survivors of South India’s 2018 Nipah outbreak in Kerala, with the goal of engineering these antibodies, leveraging synthetic DNA technology and delivering them directly to patients. These antibody therapies would be ready to attack the virus and boost the body’s ability to fight infection. The goal is to provide an immediate protection while the body builds a long-lasting immune response to immunization.
Just two floors away at Wistar is the lab of Luis J. Montaner, D.V.M., D.Phil., director of the HIV-1 Immunopathogenesis Laboratory and HIV Program leader, who is also focused on a cure, but for another infectious disease – HIV/AIDS.
There are approximately 37 million people living with HIV worldwide and 21.7 million are receiving antiretroviral therapy (ART), according to the World Health Organization. ART suppresses the HIV virus and reduces disease progression, helping people with HIV live longer and preventing onward transmission. However, ART does not eliminate infection and has to be taken daily for life, thus the priority to move HIV cure research forward.
Montaner’s 20+ years of HIV/AIDS research at Wistar has propelled him into his largest research project: the BEAT-HIV Delaney Collaboratory. He oversees a consortium of more than 80 top researchers from academia, government, nonprofit, and industry working to define the most effective way to combine immunotherapy regimens to advance new cure-directed efforts against HIV through new preclinical research and clinical trials. Their work centers on investigating where HIV hides after therapy and testing novel clinical strategies ultimately aimed at a cure that eliminates the hidden virus.
The consortium has three important goals, including two first-in-class clinical HIV cure-directed studies:
1) identifying where and how HIV hides in the body of people on antiretroviral therapy to better determine new strategies to kill the virus;
2) stimulating the innate immune system to be stronger against HIV, combining a medication called pegylated interferon alpha 2b, which may help control viruses, and potent antibodies that can neutralize HIV; and
3) introducing new “killer T cells” by bringing together two promising gene therapy strategies, independently tested in humans, with the goal of engineering, growing and administering killer T cells that are uniquely empowered to find and kill HIV-infected cells.
“Lifelong stigma, economic burden on society, strain on healthcare resources, and sheer toll on human life across the globe makes finding a cure a top priority,” said Montaner. “Together, we’re building on our teams’ extensive and established efforts to move forward and make those next transformative steps that will bring us closer to an HIV cure within our lifetime.”
Wistar scientists are dedicated to the design and creation of vaccines and therapies to stem the tide of the global burden of disease. Research is one major piece of an integrated push across communities, governments and countries for the best global health outcomes.