New Horizons for Immunology and Vaccine Research at Cincinnati Children’s
Post Date: May 2, 2025 | Publish Date:
Immunology and Vaccines
Research Annual Report 2024
From the days of Dr. Albert Sabin, Cincinnati Children’s has served as a national and global leader in vaccine and immunology research.
Breakthroughs developed here have saved hundreds of thousands of lives from childhood killers like polio and rotavirus. More recently, the Cincinnati Children’s Vaccine Research Center, led by Robert Frenck, MD, and team, played a central role as a pediatric and adult testing hub for multiple COVID-19 vaccines, with ongoing studies evaluating newer intranasal versions.
For years, Cincinnati Children’s has been among the few centers nationwide that help set the recipes for annual influenza vaccines. Looking forward, a far-reaching study of mother-infant dyads, led by Mary Allen Staat, MD, MPH, and colleagues, may help scientists develop new, longer-lasting flu vaccines.
Meanwhile, ongoing research here contributes to vaccine hunts for norovirus, RSV, Ebola, Shigella, and more. Vaccine development, however, is just one element of a wider research mission to decode even more of the secrets of the human immune system. That mission reaches into many fields from cancer prevention to infectious disease treatment to controlling autoimmune diseases. Two developments occurring in fiscal 2024 will help shape the future of this work.
Chandrashekhar Pasare, DVM, PhD, who joined Cincinnati Children’s in 2018 as a professor, now serves as director of the Division of Immunobiology.
“Dr. Pasare is considered a world leader in understanding the communication between innate and adaptive immune systems” says Tina Cheng, MD, MPH, director of the Cincinnati Children’s Research Foundation, chair of Pediatrics, and chief medical officer. “We are thrilled that Dr. Pasare will be building upon those successes and expanding research in other promising areas.”
Also, Cincinnati Children’s broke ground on a new building for the Vaccine Research Center, the Discover Together Biobank, and a long-term cold storage archive for research samples. The new Winslow Research Pavilion will will host about 70 employees.
“The Winslow Research Pavilion will enhance our efforts to connect scientists and clinicians, which enables faster translation of discoveries from the lab to directly impacting patients,” Cheng says.
Discoveries from immunology research often apply to many fields of medicine.
In cancer research, a study published in Nature Immunology, led by co-corresponding authors Nathan Salomonis, PhD, and H. Leighton Grimes, PhD, describes the world’s most detailed atlas of hematopoietic stem and progenitor cells (HSPCs), with significant implications for future leukemia research.
Meanwhile, experts at Cincinnati Children’s helped build a new research tool to accelerate cancer immunotherapy development.
Please also explore how a woman’s immune system adjusts during and after pregnancy with implications that could extend into vaccine research and organ transplantation.
Read more about these immunology and vaccine-related research highlights from fiscal 2024:
Taking the STING Out of Runaway Inflammation
Pasare and colleagues also led a study published in the journal Cell Reports, that offers important new details on how two elements of our body’s immune system clash with each other to prompt a chain of reactions that can release deadly floods of cell-killing, organ-damaging cytokines.
The work focuses on an interaction between Tem cells and the expression of Tmem173, which encodes for stimulator of interferon genes (STING). The STING pathway is known to be important for detecting viral infections. But when Tem cells harm dendritic cells, STING teams up with the gene TRAF6 and the transcription factor NFkB to form an “axis” of activity that drives runaway production of innate inflammatory cytokines.
“These findings have implications for both autoimmunity as well as cancer,” Pasare says. “We have discovered an independent cell signaling pathway that allows effector memory T cells (Tem) to become a critical driver of innate cytokine storms.”
With a pathway defined, next steps include confirming whether medications that target key points along the pathway can disrupt the inflammation cycle before it becomes uncontrollable.
Shedding Light on the Maternal-Fetal Interface During Pregnancy
Maternal CD8 T cells have the unenviable task of preserving tolerance to fetal antigens while at the same time having to fight potential infections during pregnancy. A study published in JCI Insight by Shweta Mahajan, PhD, Tamara Tilburgs, PhD, and colleagues sheds important new light on the roles and types of immune memory cells active during pregnancy.
The team found distinct populations of antigen-specific CD8+ T cells in the decidua layer of the uterus. They found two clusters of effector memory T cells that are shared in blood and decidual tissues and nine types of memory T cells uniquely found in decidua and not in blood.
The co-authors say this work will support a variety of future studies that eventually may help resolve placental inflammation, for example by suppressing excessive anti-fetal responses or by activating maternal effector cells to clear infections.
Immune Cells Carry a Long-Lasting Memory of Early Life Pain
A growing body of research has shown that the human body can “remember” the pain of newborn injuries—including life-saving surgeries—all the way into adolescence. Now research led by experts at Cincinnati Children’s pinpoints how and where the genetic changes that create such long-lasting pain memory occur.
According to their study published in Cell Reports, key changes are occurring in developing macrophage cells—one of the major elements of the immune system.
“Our experiments help to further confirm how pain memories affect female newborns for longer periods of time. Specifically, our data indicates that an epigenetic change occurs in macrophages after an early-life injury, which in turn promotes more-intense pain responses to other injuries that occur later in life,” says corresponding author Michael Jankowski, PhD, associate director of the Pediatric Pain Research Center at Cincinnati Children’s.
In mice, blocking the p75NTR receptor blunted the ability of macrophages to communicate to sensory neurons and partially prevented prolonged pain-like behaviors. However, more study is needed to determine if similar methods can be safely used to target human macrophages.
Live Vaccinations Appear Safe for Organ Transplant Recipients
Live vaccinations provided to children who previously received liver or kidney transplants were found to be safe and protective against several conditions, according to an 18-center clinical trial published in JAMA Network Open.
The study was co-authored by Lara Danziger-Isakov, MD, MPH, at Cincinnati Children’s and Amy Feldman, MD, MSCS, of Children’s Hospital Colorado. The findings are important because the rates of measles, mumps and chicken pox are rising nationally and internationally. Vaccinations can help reduce the risks faced by immunocompromised children, Danziger-Isakov says.
Pandemic Has Receded but COVID Studies Continue
One of the many surprises from the COVID-19 pandemic was the observation that children tended to experience less severe disease than adults. An NIAID-supported study co-led by Mary Allen Staat, MD, MPH, at Cincinnati Children’s, and published in the journal Cell, helped explain why.
Adults exposed to the SARS-CoV-2 virus typically produce antibody levels that spike for a few weeks, then decline. By contrast, exposed infants and young children produce antibody levels that stay high for almost a year.
In addition to this difference in response, children were found to have high levels of type 1 interferon in their noses—a potent antiviral cytokine in a critical location. Meanwhile, unlike adults, infected young children did not express high levels of inflammatory cytokines in their blood.
These differences pose implications for future vaccine research. Experts say ongoing COVID infection tracking remains important for helping children still experiencing the most severe pediatric outcome: COVID-related multisystem inflammatory syndrome in children (MIS-C).
An analysis led by Anne Jackson, MD, MPH, and colleagues at Cincinnati Children’s identified cases of MIS-C in 2023 by tapping into an administrative database of 47 children’s hospitals across the U.S. The findings published in JAMA Pediatrics suggest that CDC-collected data has not been capturing all cases.
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About this blog
The Research Horizons blog features news and insights about the latest discoveries and innovations developed by the scientists of Cincinnati Children's. This blog does not provide medical advice, diagnosis, or treatment.
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