As the nurse feels his lymph nodes, checks his pulse, and examines his skin, Vermont resident Charles Brooks, age 44, reflects on how it feels to join a clinical trial. “I’m interested in the scientific process. I like participating in it firsthand and doing what I can to help with developing cures for disease,” Brooks says.

During her checkup, Olivia Tarney, age 27, remarks on the importance of demystifying clinical trials participation. “It’s not scary, it’s just like a series of doctor’s appointments,” says Tarney, a recent UVM public health graduate.  “I feel that science and public health are so important, and this helps move science forward.”

Tarney and Brooks are voluntarily participating in a clinical trial for an experimental treatment for dengue, a mosquito-borne viral disease that poses a growing risk in tropical regions worldwide, including the United States. Supported by the National Institutes of Health (NIH), this trial is testing a monoclonal antibody, a protein engineered to stimulate the immune system to attack a specific pathogen. 

Following an initial screening and examination, volunteers are randomly assigned to receive either the investigational product or a placebo prior to receiving a dose of a mild strain of dengue virus. The weakened virus has been shown to cause a rash but not dengue fever. The volunteers attend regular follow-up visits at the Clinical Research Center at the UVM Medical Center for physical exams and blood draws. 

Meanwhile, on the other side of the University of Vermont campus, scientists and research technicians process and analyze the blood samples to document the volunteers’ immune system responses to the virus and evaluate how quickly the virus vanishes from their bloodstream. The lab staff chills the blood, spins it in a centrifuge to separate red and white cells, and examines the clear serum to count virus particles. Researchers use this information to determine how the new product affects the volunteers’ ability to avoid dengue infection compared to placebo and to determine the doses at which it may be effective.

About 80 volunteers are participating in the study at two sites: the University of Vermont Larner College of Medicine and the Johns Hopkins Bloomberg School of Public Health in Baltimore. While there are no cases of dengue in Vermont, scientists in the Green Mountain State have led efforts to develop an effective vaccine for it since 2009. This latest study expands this work with a non-vaccine preventive measure, monoclonal antibodies. 

This research is one of about 10 trials currently under way by the Vaccine Testing Center (VTC) at the Larner College of Medicine. Founded in 2001 by Beth Kirkpatrick, M.D., professor and chair of the Department of Microbiology and Molecular Genetics, the VTC has earned a reputation for tackling some of the most pressing problems caused by infectious diseases. Working with the Clinical Research Center at the UVM Medical Center and collaborators across UVM’s campus, the VTC has tested treatments for a multitude of infectious diseases afflicting people across the globe, helping to drive innovation and improve outcomes for patients.

“Thanks to the clinical trials conducted by Dr. Kirkpatrick and her team at the VTC, in partnership with our world-class academic medical center, our college and community have benefitted people around the world.” 

— Larner College of Medicine Dean and UVM Chief Medical Affairs Officer Richard L. Page, M.D. 

A remarkable feature of the VTC is its relationship with community volunteers, like Brooks and Tarney, who collaborate with the research team to create vaccines and treatments that will improve health, prevent illness, and reduce the enormous impact of infectious disease. “We have always relied on community volunteers. We work very hard to have good relationships. Without their support we couldn’t do this research,” Kirkpatrick says.

This year, as the VTC marked its 24th year of operation, Dr. Kirkpatrick handed her director’s reins to new co-directors Kristen Pierce, M.D., professor of medicine, and Mary Claire Walsh, PA-C, research program administrator and infectious disease physician assistant. “Dr. Kristen Pierce and Mary Claire Walsh are exceptional and dedicated clinical researchers, astute and careful clinicians, and really wonderful people,” Kirkpatrick says. “The VTC is in good hands and I’m happy they have the opportunity to take the VTC in new and exciting directions.”

Kirkpatrick remains committed to her vaccine research and her work as an attending physician at the UVM Medical Center. She continues to serve as chair of the Department of Microbiology and Molecular Genetics, which spans the Larner College of Medicine and the College of Agriculture and Life Sciences, and she holds a secondary appointment in the Department of Medicine. She is principal investigator for the Translational Global Infectious Diseases Research Center, a National Institutes of Health–funded Center of Biomedical Research Excellence at UVM. She also serves on a World Health Organization international research committee that helps define and fund polio research around the world. 

As she looks forward to spending time focusing on where to take the field next, Kirkpatrick reflects on her passion for vaccine research and the success of the research center she created.

Why Vaccines, Why Clinical Trials?

The intersections of medicine, history, philosophy, and public health have long fascinated Kirkpatrick. She majored in biology and political theory as an undergraduate at Bates College, where she “spent many hours in the library thinking about issues of liberty, human rights, and poverty,” Kirkpatrick says. Through microbiology classes in medical school, she developed a keen interest in infectious diseases that impact low- and middle-income countries. As an example, she points to data showing the close links between a nation’s disease burden and its wealth. “The poorest countries have 50 times the burden of infectious diseases that the wealthiest countries have. The disparity is dramatic and unjust, and it compels me to work on preventive measures like vaccines.” 

Kirkpatrick earned her M.D. at Albany Medical College and completed an internal medicine residency and chief residency at the University of Rochester, followed by subspecialty training in infectious diseases research at Johns Hopkins School of Medicine where she gained foundational experience in microbiology, immunology, and running human vaccine trials. She studied clinical tropical medicine in Lima, Peru. While in Thailand working at a mission hospital, Kirkpatrick contracted dengue, which she says might have sparked a particular interest in this infection. “There’s nothing like having a fever of 103 degrees for a few days to focus the mind,” she notes. More seriously, “I believe that no one should suffer or die from a severe illness that can be safely prevented.”

Vaccines have been so successful that many people cannot grasp why they are important, Kirkpatrick says, explaining that, at the start of the 20th century before vaccines existed, the top causes of death in children in the U.S. included infectious diseases, such as measles, diphtheria, and respiratory and enteric infections. Today, because of vaccines, most U.S. clinicians have never seen many of the vaccine-preventable illnesses in children or adults. These same diseases continue to infect and kill large numbers of people in low- and middle-income countries. 

“I believe in the importance of preventing illness, and death, through public health and preventive measures. Developing vaccines is high-value research and it deserves to be a cornerstone of medical inquiry,” 

— Beth Kirkpatrick M.D. 

Kirkpatrick joined the University of Vermont faculty in 1999. While her appointment initially focused on clinical care, her interest in vaccine studies and human immunology inspired her to continue and expand her research. In 2001 she received an opportunity to collaborate with Johns Hopkins researchers on a clinical trial for a vaccine to prevent typhoid fever, caused by Salmonella Typhi. All she needed was a laboratory and staff.

The Rise of the Vaccine Testing Center

Clinical trials with human subjects are very formal studies that follow strict federal regulations around the ethical treatment of volunteer participants, and this requires numerous facilities and “an army of well-trained and dedicated staff,” Kirkpatrick says. A single trial involves 12–20 employees, including coordinators who recruit, screen, and communicate with volunteers; a regulatory expert to make sure that federal regulations are met for the U.S. Food and Drug Administration and the Institutional Review Board; nurses to inject vaccines and monitor volunteers; clinicians to carefully track the subjects and minimize any unexpected side effects; a laboratory team to process and analyze the samples; and one or more faculty investigators who initiate and guide the study, manage the team, and scour the data. 

For this initial vaccine study, Kirkpatrick says she “borrowed an outstanding clinical coordinator, Cathy Larsson,” from UVM’s infectious disease division to manage the trial. She received permission to use an abandoned lab space on North Prospect Street and recruited an infectious disease fellow, Brad Robinson, M.D., to assist with care of the volunteers, who were seen in a clinical space at the University Health Center. The name of the enterprise came from necessity: “We were recruiting volunteers from the community and needed to refer to ourselves as something! So, we simply called ourselves the UVM Vaccine Testing Center.”

With this amount of work to build infrastructure, “you are now set up to do many studies,” Kirkpatrick says. She looked for more clinical research opportunities, applied for grants, recruited faculty investigators, and expanded and trained talented staff, building a multidisciplinary team.

According to co-director Walsh, who joined the VTC in 2008, much of the progress made during the past two decades traces back directly to Kirkpatrick’s leadership and clarity of purpose: “Beth’s mentorship and persistence have shaped not just the direction of the VTC, but the culture within it. Our work isn’t just about producing strong research—it’s about how we approach it, and the values that guide us. We’re fortunate to work with people who are not only skilled and dedicated, but also curious, thoughtful, and committed to doing things well.”

Early trials focused mainly on vaccines for enteric infections including typhoid, cholera, and campylobacter, a food-borne bacteria considered to be among the most common bacterial causes of human gastroenteritis worldwide. One of the first trials the VTC worked on was for anthrax, a bacterial infection that was used as a bioterrorism agent after the September 11, 2001, attacks against the U.S. “Senator Patrick Leahy was sent anthrax in the mail, and we all worried about bioterrorism attacks,” Kirkpatrick says, recalling the October 2001 incident. “We studied one of the new anthrax vaccines. It was important to the United States, and to Vermont, so it was important to us, too.”

Current Trials

VTC personnel includes five core faculty researchers and 15 staff members, including clinical coordinators, laboratory professionals, a statistician, a recruiter, and administrators. 

The team is currently involved in a variety of clinical trials in various stages of research. Pierce is principal investigator for the dengue monoclonal antibody trial and for a worldwide Phase 3 clinical trial for a Lyme disease vaccine. Sponsored by Pfizer, the Lyme vaccine study is under way at 36 sites where this tick-borne disease is highly endemic, including the northeastern U.S. and Northern Europe. The trial commenced in fall 2023 and is scheduled to conclude in November 2025. Also with Pfizer, the team hopes to participate in a new phase 3 trial to test a vaccine against Clostridium difficile, the most common cause of infectious diarrhea in health care settings.

Jessica Crothers, M.D., associate professor of pathology and laboratory medicine, leads two clinical trials to develop better polio vaccines. Although rare in North America, polio remains a threat due to outbreaks in politically unstable regions around the globe. A 2021 UVM trial, funded by the Gates Foundation, tested a genetically modified oral vaccine designed to prevent reversion to a disease-causing form. A second trial, launched in 2022 with WHO and the Global Polio Eradication Initiative, is evaluating an injectable vaccine enhanced with a mucosal adjuvant to boost gut immunity and reduce virus shedding.

Benjamin Lee, M.D., associate professor of pediatrics, investigates how undernutrition affects the gut microbiome and immune development in Bangladeshi children. He also studies diarrheal diseases like rotavirus and adenovirus, and he leads the pediatric arm of the Lyme vaccine trial. With NIH funding, he’s investigating why some vaccinated children remain vulnerable to infectious diseases even when vaccinated, building on eight years of his research at UVM. Lee and Crothers are collaborating on a separate project to examine the infant gut microbiome and how this relates to immunity to vaccines for rotavirus and polio.

Investigations by Sean Diehl, Ph.D., associate professor of microbiology and molecular genetics, seek to understand the immunologic mechanisms occurring in immune cells and antibodies that protect against dengue and Zika viruses, as well as norovirus and sapovirus. Diehl’s research leverages the massive clinical specimen banks of the VTC and its research studies in the U.S. and in Bangladesh, leading to critical discoveries about how humans respond to dengue vaccination and understanding vaccine durability. Diehl’s past research focused also on respiratory syncytial virus (RSV), one of the most common causes of acute lower respiratory infections in children globally. Findings from his postdoctoral training in the Netherlands led to the development of an RSV monoclonal antibody, called Nirsevimab, approved for medical use in Europe in 2022 and the U.S. in 2023.

Investigator-Driven, Collaborative Projects

While some of the VTC’s research studies are initiated by the pharmaceutical industry, most research at the VTC is developed and designed by the faculty researchers and funded by grants from entities including the Bill and Melinda Gates Foundation, World Health Organization, the National Institutes of Health, and the U.S. Department of Defense.

“Investigators will often pick one or two pathogens or vaccines to work on to build a significant amount of expertise in that area,” Kirkpatrick says. “The Vaccine Testing Center provides a way for faculty to have really rewarding careers in clinical and translational research. They can grow their research careers within the context of serving a medical need, and there are so many scientific and biomedical questions to be asked about the natural history of a disease, how the immune system responds to infections or vaccines, and why vaccines work better in some people than others. It’s an endless quest.”

The VTC’s largest research effort centers on dengue fever, in collaboration with NIH virologist Steven Whitehead, Ph.D., and Johns Hopkins School of Public Health (JHSPH) professor Anna Durbin, M.D. Dengue, now spreading into parts of the U.S., causes 100–400 million cases annually around the world. Since 2009, more than 27 clinical trials of Whitehead’s candidate vaccines have been conducted at UVM and JHSPH, yielding major immunologic insights. One vaccine, TV003, is in phase 3 trials in Brazil and has been licensed to five pharmaceutical companies.

Caroline Lyon, M.D., associate professor of medicine and director of hospitalist medicine at the UVM Medical Center, collaborated with colleagues at the University of Maryland and the University of Cincinnati Children’s Hospital to study a single-dose oral vaccine for cholera, an infectious diarrheal disease caused by bacteria in drinking water. While cholera has been mostly absent in the U.S. for more than 100 years, outbreaks in low-resource countries cause rapid illness and death. Lyon’s work was the pivotal study leading to U.S. Food and Drug Administration approval for this vaccine.

Since 2002, VTC researchers have collaborated with the International Centre for Diarrhoeal Disease Research (icddr,b) in Dhaka, Bangladesh, on clinical trials, observational studies, and immunology research with Rashidul Haque, M.B., Ph.D., senior scientist at icddr,b, and colleagues. In response to a massive increase in dengue virus infections in Dhaka over the past decade, their current work includes a large NIH-funded Dengue-in-Dhaka Initiative begun by Kirkpatrick in 2015. VTC scientists travel to Dhaka frequently to meet with colleagues and share skills and assays; they also invite Bangladeshi colleagues to Vermont for extended training. “We’ve done an enormous amount of work with our long-standing collaborators in Dhaka, and we really value this relationship,” says Kirkpatrick.

The COVID Pandemic

In the fall of 2020, the VTC began participating as one of the research sites needed to evaluate the efficacy of one of the new COVID-19 vaccines, from AstraZeneca. Their task was to enroll volunteers thought to be at the highest risk of COVID illness, including people over 65 years old and those from under-resourced communities. From the start, this was the largest and most rapid effort undertaken by the VTC research team. 

“Those were dark days. People were waiting for some way out of the pandemic,” Kirkpatrick recalls. “Because we had the expertise at the VTC, UVM was selected to participate. I was asked to announce it at [Vermont] Governor Scott’s press conference. That was a moment!”

To quickly launch this critical study, a new clinic site was established with help from UVM Medical Center President and Chief Operating Officer Steve Leffler, M.D., who facilitated reopening a former primary care clinic. Nurses from the Clinical Research Center joined the effort, and a large team of study staff was hired and rapidly trained. Volunteers at the highest risk for COVID were recruited, educated, and committed to the two-year trial. The goal of 250 participants was reached in just four weeks, with more than 4,500 people registering. The study closed in December 2022. The AstraZeneca vaccine was later approved in multiple countries, saving an estimated 6.5 million lives in its first year.

Cultivating Success

As part of an academic health system, the VTC serves to train the next generation of researchers and providers to advance treatments that prevent illness and reduce impacts of infectious disease. Over the years, numerous VTC coordinators, statisticians, and laboratory workers who trained at the VTC furthered their careers as physicians and research leaders.

Class of 2028 medical student Andrew Root worked for the VTC before starting medical school, assisting with community volunteers’ medical visits and processing samples with the laboratory team. “Participating on a team conducting promising vaccine research with global impacts helped me realize that this was exactly the scientific and medical community where I wanted to begin my medical career,” says Root, who has personal family experience with pediatric polio and life-extending treatments found through research. 

Through her work with the Translational Global Infectious Diseases Research Center, Kirpatrick focuses on supporting emerging faculty investigators and growing institutional strength in this research area. Her mentorship has fostered the careers of many scientists and medical professionals, including VTC co-directors Pierce and Walsh.

“Beth taught me many things about clinical research and leading a team. She will always recognize people publicly when good things happen and she always strives to nominate faculty and staff alike for awards. She recognizes that others’ success is her success.”

— Kristen Pierce, M.D. 

Walsh says her career has been deeply influenced by the people and projects of VTC and Kirkpatrick’s clear and ambitious vision for what the center could become. “When I joined the VTC, I couldn’t have predicted how much this place—and the people here—would shape my career,” Walsh says about stepping into the VTC co-director role. “The environment Beth fosters—one that values rigor and teamwork—is a community that challenges and supports each other in equal measure. That spirit is what keeps the VTC evolving.”

What is a Vaccine Clinical Trial?

Clinical trials are research studies designed to test new biomedical products that are not yet licensed for use in people. These “investigational products” include medicines, vaccines, and devices. Before approval for widespread use in the U.S., vaccines must undergo a series of trials in phases to demonstrate safety, tolerability, immune responses, and efficacy. 

Early-stage vaccine trials recruit healthy people to help answer specific questions about the safety and tolerability of the candidate vaccine. All trials include a placebo group—participants who receive an inactive treatment—so any side effect, such as headache or fatigue, can be compared to rates in the non-treated group. All trials are conducted by qualified clinicians and are closely reviewed and monitored by the U.S. Food and Drug Administration and by local ethics committees, called Institutional Review Boards, to ensure the protection of participants’ rights and welfare. Participating in a clinical trial is voluntary.

Vaccine clinical trials involve several phases:

Phase 1: To test a vaccine’s safety, it is given to 10–50 healthy volunteers, in the smallest dose possible. After dosing, the volunteers are closely monitored to see how they tolerate the vaccine and observe how it affects their immune systems. Most vaccines and medications do not make it past phase 1.  

Phase 2: Vaccines that survive phase 1 are tested on 100–300 volunteers to further assess their effectiveness and side effects, determine the best dosage or number of vaccines, and observe immune system responses.

Phase 3: To confirm a vaccine’s efficacy, or ability to prevent a disease, it is tested on participants who represent the population who will eventually use the treatment. These trials include 10,000 to more than 100,000 people. The trial can take months to years, depending on how much infection is circulating at the time. For the trial to be considered successful, there needs to be a large statistical difference in infection rates between the people who received the placebo versus those who received the vaccine. 

Human challenge trials are infrequently performed in conjunction with efficacy testing. This involves giving a dose of infectious bacteria to volunteers to test a vaccine’s efficacy to prevent the infection. VTC is one of only a few sites with the expertise to perform challenge trials.

Phase 4: Post-marketing studies performed after a drug has been licensed gather further safety or effectiveness data in routine clinical use.