UMB StaffStefan Kappe, PhD, joined the University of Maryland School of Medicine (UMSOM) in early 2026 as director of the Center for Vaccine Development and Global Health (CVD). He also serves as the Myron M. Levine, MD, DTPH, Professor of Vaccinology and vice chair for translational research in the Department of Pediatrics.
Kappe and his team of scientists focuses on understanding the complex transmission biology and pathobiology of malaria parasites and host immune responses to parasite infection, with the goal of designing interventions that are more effective than current malaria treatments and vaccines. He is internationally known for his research on elucidating the molecular determinants of parasite development in the liver and his pioneering work on genetic engineering of parasites, which has led to the development of a highly efficacious live-attenuated vaccine candidate currently in clinical trials.
Before coming to UMSOM, Kappe worked at the University of Washington in Seattle, where he was a professor and the associate vice chair of basic science research in the Department of Pediatrics. He also was a senior principal investigator at the Center for Global Infectious Disease Research at Seattle Children’s Research Institute, where he had served as an associate director.
Kappe has received more than $34 million in funding from the National Institutes of Health (NIH) and other funding sources such as the Gates Foundation since 2003, and he continues to have strong NIH funding support through P01, R01, and U01 grants. With a significant h-index of 65, Kappe’s research has been cited more than 6,300 times.
He earned his PhD in molecular biology and parasitology from the University of Notre Dame and undergraduate degree in biology from the Rheinische–Friedrich Wilhelms University in Germany.
Kappe recently sat down with CATALYST magazine to discuss his research, the effects the current political and funding environment is having on vaccines, and his long-term vision for CVD.
Your career has been deeply rooted in malaria research, particularly understanding the parasite and developing new approaches to vaccination. What have been the most important advances in your own malaria research, and what questions are you most focused on answering now?
Malaria is an ancient disease caused by infection with Plasmodium parasites that are transmitted by mosquitoes. Human malaria is caused by six distinct Plasmodium species, and two of those, Plasmodium falciparum (the No. 1 cause) and Plasmodium vivax (the No. 2 cause), cause most human malaria cases. Today, malaria continues to inflict tremendous suffering around the world, with more than 200 million malaria cases and more than 500,000 deaths annually. Most affected are young children and pregnant women. After more than a century of malaria research, the world remains engaged in an arms race with the parasites, particularly for malaria treatment, which constantly faces the development of drug resistance and treatment failure. For vaccines, we currently have two modestly effective malaria vaccines for Plasmodium falciparum; good progress but not enough to contemplate the eradication of malaria.
One of the goals of my research team and our collaborators is the development of a live-attenuated Plasmodium falciparum malaria vaccine. We are using CRISPR technology to engineer the complex genome of this eukaryotic pathogen to make a vaccine that it is safe and can induce potent protective immune responses after vaccination. Our vaccine strain, called LARC, is alive, infects the liver, and replicates, but LARC cannot leave the liver and therefore cannot cause pathogenetic blood stage infection. Recent clinical trials have shown that the LARC vaccine is safe and well tolerated in adults and children and that a single dose of LARC provides 90 percent protection against a virulent parasite challenge. Our collaborators are currently conducting Phase 2 clinical trials with the LARC vaccine in West Africa. In the lab, we are continuously working on further improvement of LARC vaccines to increase their potency and broaden their protective efficacy.
I am deeply convinced that the transformational new interventions for infectious diseases will grow from our deep understanding of pathogen biology and the advanced knowledge we can garner to understand interactions of pathogens with their human host, particularly the immune system. In my lab, you will find scientists who study the molecular mechanisms that control parasite infection of mosquitoes, control the growth of the parasite in the mosquito and the molecules that enable liver infection and parasite replication within hepatocytes. We also study how the human immune system responds to liver infection, which occurs without any symptoms, and which part of the immune response mediates protection from infection.
Malaria also illustrates the importance of basic science in ultimately producing new vaccines, treatments, and prevention strategies. Where does basic infectious disease research stand today, and what areas of discovery do you believe are most likely to lead to the next major breakthroughs worldwide, and more specifically at CVD?
Basic and translational research are fundamental to improving human health. Without research, no new medical interventions would be possible. Research on infectious diseases has ignited the development of new drugs and vaccines that are used today to fight some of the most devastating diseases; for example, viral infections such as measles and polio as well as bacterial infections. However, for some of the most devastating infectious diseases, we don’t have the best drugs and vaccines. For example, tuberculosis, HIV, influenza, and malaria still defy our efforts to develop better interventions. We just need to go back to the drawing board, not walk on well-trodden research paths, and we must invent new and disruptive ways to combat infectious diseases. This is what we have done to develop our current LARC malaria vaccine.
We have seen extraordinary advances in vaccine science in recent years. Where do the most promising vaccine candidates and clinical trials stand today, both for malaria and other infectious diseases, and what are the biggest scientific hurdles still to overcome? Furthermore, how does climate change play into the future of infectious disease research?
These are big questions. For malaria, I believe that currently our LARC vaccine is the most promising candidate and there are some great advances in adding components to the currently licensed malaria vaccines. There are manufacturing challenges with whole cell vaccines such as LARC; making them at a scale that can yield the hundreds of millions of vaccine doses needs innovation in vaccine production.
For viral infections, the biggest challenge is inventing vaccines that can protect against the great variability and mutability of a given virus and can also protect against future variants. The HIV vaccine field, for example, has not overcome this challenge yet. We have all experienced COVID, when the first vaccines developed soon lost efficacy because the virus changed, necessitating the frequent update of the vaccine to match the new viral variants. And of course, flu, for which the development of a universal flu vaccine has made progress but appears to be still facing tremendous obstacles.
Climate change has really been a wild card for infectious diseases. What is clear is that infectious disease spread changes with changing climate. This is particularly true for vector-borne diseases, caused by pathogens that hitch a ride with biting insects and ticks. With changing climate and ecology, tick-borne diseases have vastly expanded their range within the U.S., affecting many more people now. Dengue, a mosquito-borne viral infection, is taking a foothold in the U.S., and I believe will become a major public health threat.
We at CVD are studying infectious diseases in the context of climate change, not only to predict future changes in occurrence of disease but also to figure out how we can devise measures to become more resilient to these changes.
Antimicrobial resistance is an increasingly urgent global health threat. What role should CVD play in advancing antimicrobial research, and how do you see vaccine development, therapeutics, diagnostics, and basic science working together to address emerging and drug-resistant pathogens?
Microbial drug resistance is an enormous threat to human health. It is a constant arms race of pathogens evolving resistance to the drugs currently in use and humans developing new drugs or drug combinations to overcome resistance. We at CVD are focused on vaccines in the context of drug resistance. When microbes become resistant to an antibiotic, they are still very susceptible to the powerful human immune responses that we can stimulate with vaccines. If we vaccinate in time, it will work to protect against drug-resistant pathogen infection. We will also have to be more innovative to find smart ways to treat resistant pathogen infections by harnessing the immune system.
Emerging pathogens are an important area for CVD. The next pandemic is surely around the corner, but we don’t know what pathogen it will be and where it will arise. Therefore, we need to understand much better which group of pathogens infecting animals has the highest likelihood to mutate in a way that allows it to jump from animal to human and cause disease. This is a big task, but I believe that artificial intelligence-driven approaches will be critical in this research arena.
You have taken the helm of CVD at a time when infectious disease research is facing both enormous scientific opportunities and a challenging political and funding environment. How is that climate affecting the field, what do you see as the next major frontier in infectious disease research, and what is your long-term vision for CVD’s role in leading it?
Scientific breakthrough discoveries have been accelerating at a great pace in the past decade, not only in infectious disease research but also oncology. It is unfortunate that just in this moment, the federal government steps on the brakes and greatly limits support for research. In addition, we, who work on vaccines, face new and irrational challenges to vaccines. Vaccines are miracles of medicine that save lives. Diseases for which we have safe and highly effective vaccines are coming back rapidly, for example, measles, and it is disturbing to see that protecting our children with vaccines is becoming a victim of political ideology. We need to stand our ground and continue in our unwavering efforts to bring forward new and innovative vaccines to people in need. My role is focused on ensuring that our scientists and clinicians are supported and can continue their work. We can accelerate progress by recruiting scientists who bring novel and integrated approaches to vaccine development, infectious disease research, and global health. I believe that the use of artificial intelligence (AI) approaches in research will be transformational. We need to embrace AI as a tool to discover the unknowns and find novel paths forward for interventions that we have not yet conceived.
