Alumnus Sean Diehl’s research was instrumental in RSV vaccines. He has expanded his work as Zika and dengue regions spread.
By Keith Walters ’11
As our planet continues to warm, mosquito-borne diseases like Zika and dengue are finding new territories to thrive in, including areas where they were previously rare, such as Europe and parts of the United States. This shifting health landscape underscores the vital role of immunology researchers like Sean Diehl ’98.
Diehl, associate professor of microbiology and molecular genetics at the University of Vermont, has spent his career searching for solutions to some of the world’s most pressing health challenges. For example, he and his research team were instrumental in developing technology used to discover an antibody to prevent respiratory syncytial virus (RSV) disease in infants. The Federal Drug Administration and Centers for Disease Control and Prevention approved Nirsevimab in 2023.
“My personal fulfillment comes from being able to translate my work toward interventions that can improve health on a large scale,” says Diehl.
Diehl always had a passion for science. Mentors like SUNY Distinguished Teaching Professor Emeritus of Biology Robert O’Donnell and Sid Bosch, professor of biology, shaped his academic journey and steered his curiosity toward immunology.
“I credit Professor O’Donnell with getting me interested in the frontier of immunology—where the answers were few, but the potential so great, such as understanding mechanisms of how the immune system fights off disease. It was clear then and is evident today that understanding how the immune system works can lead to new vaccines or new ways to fight cancer, ” Diehl says.
Diehl earned his doctorate in cellular and molecular biology with a focus on immunology at the University of Vermont. His post-doctoral research at the University of Amsterdam on harnessing the body’s natural protective abilities was the basis of his work that contributed to new protective measures against RSV.
“We’re full of medicines in our own body, in the form of antibodies,” Diehl explains. He and his team set out to develop a method to produce these antibodies. The antibodies would be transferred to individuals unable to mount an effective immune response, such as infants and older adults.
The challenge, says Diehl, was discovering a way to refine the process of antibody production. “For more than a hundred years, people received passive immunizations,” Diehl says, which means inoculating individuals with blood plasma from someone who had recovered from an infection in an attempt to transfer the protective antibodies.“It is imprecise and can cause adverse reactions in the recipient.”
“The problem is that antibodies against almost every infection you’ve ever had are found in the blood and it’s very challenging to purify the exact forms that are protective against a specific disease,” he says.
Sean Diehl ’98 is now researching dengue and Zika, which have become more widespread. (Photo provided by Sean Diehl ’98)
The solution? Focus on the cells that manufacture antibodies, known as B cells. Diehl’s team sought to understand the key steps that activate a B cell when it encounters a virus—and how to stimulate it to produce antibodies en masse.
The team’s work in Amsterdam involved painstakingly piecing together the immune response puzzle. The goal, says Diehl, was to coax a B cell into a state of high productivity, as if it were responding to a real threat. This research ultimately yielded the antibody, called D25, that became Nirsevimab. In addition, D25 was used to guide development of two other vaccines for RSV that were approved in 2023 for expectant mothers and for people over 60 years old.
“The beauty of B-cell research,” says Diehl, “is that it can be applied to anything.”
Diehl uses the same research methods at the University of Vermont to confront Zika and dengue, which affect nearly 400 million people annually, particularly in tropical regions. Dengue can incapacitate individuals for weeks, and Zika was linked to birth defects in Brazil in 2015.
Diehl is hopeful about the progress in dengue vaccine development. An ongoing clinical trial in Brazil shows promising results.
“Within five years, we anticipate a dengue vaccine that protects even those who have never been exposed to the virus,” he says.
Creating a Zika vaccine is more complex. Despite various developed strategies, testing is challenging because the virus hasn’t been widely circulating since 2015.
“These viruses can cause immense suffering, and vaccines could prevent it,” says Diehl. “The fight against these diseases is not just a scientific challenge—it’s a humanitarian one.”
