The Past, Present, and Future of Vaccinology

Researchers at Dartmouth Health Children’s make advancements in vaccine development for COVID-19, polio, and other diseases.

In many people’s view, little good came out of the coronavirus pandemic. However, for virologists and vaccinologists at Dartmouth Health Children’s, the past three years have been full of discovery and exciting medical advancements.

Despite the losses and hardships of the pandemic, the novel mRNA vaccines represent a shining accomplishment in helping to bring the pandemic under control. Jason McLellan, PhD, then-professor at Geisel School of Medicine, started laying the foundation in 2014, collaborating with colleagues at Dartmouth and elsewhere to learn how to stabilize the spike proteins common to all coronaviruses in order to make a better vaccine. McLellan’s breakthrough discovery in 2016 of the structure of the coronavirus spike protein led to the speedy development of the mRNA vaccine for the SARS-CoV-2 outbreak in 2020. Their achievement has saved millions of lives around the world.

“That’s a success story that doesn’t happen every day— some people don’t have it happen in their whole career,” says Peter Wright, D ’64, MD ’65, a pediatric infectious disease specialist at Dartmouth Health Children’s who immediately began studying the immune responses of infected people during the first wave of the pandemic.

The technology McLellan and others developed led to an agreement with Moderna, manufacturer of the vaccine, to generate royalties for Geisel. Wright is already working on research that focuses not only on antibodies that prevent viral infections in vaccinated people, but also those with the potential to reduce transmission of viral infections from person to person.

Expansive Vaccine Research

Dartmouth Health Children’s has a long history of vaccine research and development, far longer than COVID-19 has been around. Wright and other clinical

Remembering Dr. Sam Katz childrens.dartmouth-health.org researchers have contributed to vaccine development for many other pediatric diseases, such as polio and respiratory syncytial virus (RSV) infection.

Dartmouth alumnus Samuel Katz, D ’48, MD ’50, HON ’98, was an influential and world-renowned virologist who helped develop the measles vaccine, which has saved countless lives over the past 60 years. Katz died in October 2022 at age 95.

Born and raised in Manchester, New Hampshire, Katz completed his undergraduate studies at Dartmouth College and then earned his MD degree at Dartmouth Medical School and Harvard Medical School.

Peter Wright, D ’64, MD ’65, is studying why an oral vaccine that triggers an immune response in the gastrointestinal tract can prevent viral infections in the respiratory tract.

“Polio has been a remarkable model to study because we have two effective vaccines. The inactivated vaccine is highly effective at preventing paralytic disease but doesn’t prevent the virus shedding from the gastrointestinal tract, where it can spread to other people,” Wright says. “We also have a live, oral vaccine that develops mucosal antibodies detected in the stool that limit person-to-person transmission.”

In his research, Wright is trying to determine why vaccines delivered orally—triggering an initial immune response in the GI tract—can be extraordinarily good at preventing infection by a virus that causes respiratory illness. “We’re trying to understand why it works and build on that both in terms of safety and effectiveness,” Wright says.

John Modlin, MD, emeritus professor of pediatrics and of medicine at Geisel, also has been studying polio for decades. An outbreak of poliovirus infections in 2022 among a small group of unvaccinated people in New York has caused him great concern. The disease has been eradicated in the U.S. for many years, so the extensive transmission of this virus—which left one young adult paralyzed—is considered a public health emergency.

Modlin recently took a leave of absence from Dartmouth to work at the Bill & Melinda Gates Foundation on a new oral polio vaccine that reduces the rare risk of polio caused by the current oral vaccine, which is widely used in low-income countries. This vaccine is only for type 2 polio; Wright is currently conducting clinical trials to develop a similar vaccine for types 1 and 3. Wright says this idea is linked to COVID-19: “The concept ties into the

Continued on page 8

Live vs. Inactivated Polio Vaccines

The version of the polio vaccine currently used in the U.S. is the injection made from a killed virus. A live vaccine given orally was used decades ago when the disease was widespread. While effective at preventing transmission, the live version could cause polio in very rare cases. When polio was eradicated throughout much of the world, U.S. public policy developed by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics determined that it was appropriate to distribute the inactive vaccine only.

Katz was a resident at Boston Children’s Hospital during a polio outbreak in 1955. The experience led him to join the lab of Nobel Prize–winning John Enders, MD, who was working on a polio vaccine. Together, Enders and Katz developed an attenuated measles virus vaccine, approved by the Food and Drug Administration in 1963.

Katz joined the Department of Pediatrics at Duke University School of Medicine in 1968 and chaired the department for 22 years. During his tenure, John Modlin, MD, emeritus professor of pediatrics and of medicine at Geisel School of Medicine, was a medical student.

“I was drawn to this new and exotic field of viral disease and vaccines,” Modlin said. “As a result of Sam’s influence, I ditched my plan to go into surgery and did my residency and an infectious diseases fellowship at Boston Children’s.”

Peter Wright, D ’64, MD ’65, a pediatric infectious disease specialist at Dartmouth Health Children’s, also knew Katz at Boston Children’s.

“Sam had a tremendous name in terms of vaccine development, including later working in the areas of vaccine hesitancy and acceptance,” Wright said. “We’re building on his legacy.”

At the time, Dartmouth Medical School was re-establishing its four-year medical degree program, and it needed to provide education in the subspecialty. Plus, this expertise was urgently needed in the region.

“Babies started coming immediately, so we had to get ready in a hurry,” remembers Little, emeritus professor of pediatrics and of obstetrics and gynecology at Geisel School of Medicine. “There was a demand clinically and also academically. We created a clinical fellowship in neonatology and established a research component.”

The intensive care nursery (ICN) at Mary Hitchcock Memorial Hospital was equipped with ventilators, incubators, and other hightech equipment to provide specialized care. There were no other neonatology programs in the state, so Little co-founded the Vermont/ New Hampshire Regional Perinatal Program, partnering with the University of Vermont

Contributions to Global Medicine

From early on, many people in the Division of Neonatology have been involved in international health, particularly in Africa and southeastern Europe. In the Republic of Kosovo, Little helped establish a foundation that’s now called Action for Mothers and Children (AMC), and he is still actively involved even after retiring from Dartmouth. Ringer has been involved for 25 years in international care, particularly in Vietnam, Ethiopia, India, and Tanzania.

Medical Center in Burlington to care for sick newborns in the region.

Knowing he could not run the program singlehandedly, Little hired Judith Frank Ketterer, MD, MS ’99, as the second neonatologist in New Hampshire. In addition to physicians, the ICN needed skilled nurses as well as social workers to help parents worried about their sick babies, so training other neonatal staff began right away.

Little understood, as did his successor, the late Bill Edwards, MD, RES ’77, FEL ’78, that neonatology must serve not only newborns, but also their parents and families. So, while other neonatal programs around the country left parents out of staff discussions about their babies, DHMC’s neonatologists welcomed them at every step.

“We became nationally known for inviting parents on rounds when medical teams got together to discuss their baby’s care, which was a major change in the way neonatal care was provided in this country,” Little says. “It involves an understanding of the effectiveness and moral reasons why parents should be involved in the decision-making process for their babies. It also involves helping parents so they can engage in that process while they’re under an extreme amount of stress. Bill Edwards was a leader at this.”

The highly innovative neonatal unit at Catholic Medical Center in Manchester, New Hampshire, can be credited, in part, to Edwards’ devotion to familycentered care. When Dartmouth-based obstetrics services moved to Manchester, Edwards saw to it that the facility was equipped to serve both newborns and their parents, including private rooms for families, which was rare at the time.

“Bill made sure the model of care was such that parents could stay with their baby as much as possible during hospitalization,” says Steven Ringer, MD, PhD, who is the third and current section chief of neonatology, taking over the program in 2015. “The majority of hands-on care is done by parents with nurse supervision, which completely changes the dynamic of neonatal intensive care. It improves parent-baby interaction and lessens parents’ anxiety. Involving parents and helping them get through the process has been enormously important for us.”

One of the greatest recent neonatology innovations at DHMC is the telemedicine intensive care nursery, TeleICN, which started around 2018. With advanced technology, neonatologists at the Children’s Hospital at DHMC (CHaD) can be virtually present in the delivery rooms for high-risk births at smaller hospitals. CHaD neonatologists can advise pediatricians with less experience in this subspecialty on the best way to care for sick and premature newborns.

“The doctors and nurses can move an iPad into the delivery room, so it’s almost like we’re right there,” Ringer explains. “So, when the baby is born, we can supervise and monitor and answer questions immediately, whether they’re questions about approach to care or practical questions. They can move the camera right next to the baby, and we can guide them through the process.”

And when the emergency has passed, CHaD neonatologists can review cases with the pediatricians at the smaller hospitals while the event is still fresh in everyone’s mind. Rather than setting up training sessions at multiple referring hospitals months later, telemedicine allows physicians and nurses to review cases anywhere within just a few days. CHaD neonatologists can also set up simulations for training— no matter how far away another hospital is.

Continued on page 8