CDC-funded New Vaccine Surveillance Network and a cohort study track vaccine effectiveness and babies’ health 
by Tom O’Neill

Titus White was working the room pretty well. He is a charmer, wise well beyond his eight weeks. The doctors were enamored. Moments later, he got his first dose of the rotavirus vaccine. 

Titus doesn’t know it yet, but he will provide important insights into the interwoven nature of health and vaccination. Both are rooted in the ongoing success stories of the Division of Infectious Disease’s Epidemiology and Surveillance Program. It includes Immunization Safety, the New Vaccine Surveillance Network and a separate cohort study at Cincinnati Children’s called PREVAIL. That’s short for the Pediatric Respiratory & Enteric Virus Acquisition and Immunogenesis Longitudinal Cohort, which focuses on the first two years of a baby’s life.

Both projects—a combined $9.6 million—are funded by the Centers for Disease Control and Prevention (CDC). Call it high-level research meets ground-level care.

Healthy Children, One Piece of the Puzzle at a Time

Last year, researcher Mary Allen Staat, MD, MPH, of the Division of Infectious Diseases, received a five-year, CDC grant for enhanced surveillance of new, vaccine-preventable diseases, as one of seven network sites across the U.S. 

From clinics to emergency departments at Cincinnati Children’s, Staat’s team enrolls children seen for acute gastroenteritis or acute respiratory infection, and then they collect stool, blood and respiratory samples.

The goal is to match up the children’s health with their vaccine histories, looking for insights into particular age-groups and risk factors for disease. Among current vaccines, Staat focuses on rotavirus and influenza, while gaining a better understanding of the epidemiology of norovirus and respiratory syncytial virus, with plans for potential vaccines and treatments in the future.

This approach has transformed not only the study of vaccine success rates for children treated for acute gastroenteritis and respiratory infections, but also how data is collected and shared. Cincinnati Children’s has the most ambitious data-collection system among the network’s seven hospitals.

“We want to fully understand the epidemiology as well as the innate factors in babies that make them susceptible to gastroenteritis and acute respiratory infections,” Staat says. “I look at us as an important piece of the puzzle in vaccine research.”

Back at the clinic, Titus’ mother cradled him as he got his vaccine. One of the licensed rotavirus vaccines in the U.S. was developed and tested by Cincinnati Children’s researchers a decade ago and has since spared millions of children worldwide from severe diarrhea and dehydration, which can be fatal. 

Statistically Significant Protection

In a study published in Clinical Infectious Diseases in December 2015, the vaccine surveillance network collected stool samples from 3,865 children who had been hospitalized or were treated at an emergency department for acute gastroenteritis during the 2012 and 2013 rotavirus seasons. 

Of those children, 502 (13 percent) had rotavirus. But among the larger group as a whole, researchers found in their vaccine histories that the two existing rotavirus vaccines, RV5 and RV1, provided “statistically significant, genotype-specific protection.”

The network enrolls about 1,000 children each year. All are local residents of their respective hospitals. Another type of resident provides some perspective here: medical residents.

“To think,” says Staat, “we used to have hundreds of children in the hospital and ED with dehydrating diarrhea and vomiting due to rotavirus. We now have residents who have never seen kids with rotavirus.”

Staat recalled that as a trainee herself in 1987, she was so optimistic to hear from researchers that a vaccine was “just around the corner.”

It wasn’t. It took nearly two decades to study and license. 

“So it’s very gratifying,” she says, “to see a vaccine to completion and then study its effectiveness over time.” 

Fab 5.

The Fab 5 (from left): Elizabeth Schlaudecker, MD, MPH; Mary Allen Staat, MD, MPH; Emily DeFranco, DO; Ardythe Morrow, PhD; and Monica McNeal, MS.

Staat has nicknamed her core team the “Fab 5,” in part because it’s an all-women research group, but also because they reflect a wide range of scientific backgrounds. 

Staat focuses on rotavirus epidemiology of infectious diseases. Elizabeth Schlaudecker, MD, MPH, also of the Division of Infectious Diseases, is devoted to the science of infant infection and maternal immunization.

Ardythe Morrow, PhD, of the Global Health Center, is Director of the Center for Interdisciplinary Research in Human Milk and Lactation and will lead the PREVAIL cohort study. Monica McNeal, MS, is a virologist in the Division of Infectious Diseases and her team processes and tests the thousands of specimens collected. 

And Emily DeFranco, DO, works on maternal fetal medicine in the University of Cincinnati’s Department of Obstetrics and Gynecology. She will lead the efforts to enroll mothers and infants for PREVAIL.

The Scientific Beauty of Unoccupied Offices

In addition to the Fab 5, about 20 of Staat’s staff at Cincinnati Children’s contribute to the surveillance network and the PREVAIL cohort study. From behind her desk, Staat motions toward her door.

“Those offices over there without staff in them, they’re out enrolling people,” she says. “They come in at 7 am to enroll kids who’ve been admitted. We have an evening crew too. It’s very labor-intensive.”

Staat says she’s heartened, but also somewhat surprised, that the CDC continues to fund programs that evaluate vaccines’ effectiveness after they have gained FDA approval. But she emphasizes their importance because vaccine strains can change over time, so they help researchers better understand the factors associated with infection.

Staat was among the authors of another 2015 study, published in JAMA Pediatrics, which showed that severe rotavirus gastroenteritis was virtually absent among U.S. children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium.

After controlling for vaccination and other factors, children with the non-secretor FUT2 polymorphism appeared statistically protected. “If you were a secretor, you were more likely to be infected,” Staat says.

That was a significant revelation. One co-author of that study, Morrow, is now leading the cohort study PREVAIL, funded by an additional $3.6 million CDC grant in 2016.

It is designed to understand the natural history of infection with common pathogens in the first two years of a baby’s life. Cincinnati Children’s was the lone hospital to receive funding for PREVAIL, in which the center will enroll 240 mothers and infants and follow them for two years.  

The Intersection of 'Oohs,' 'Ahhs' and 'Oligosaccharides'

Research staff makes home visits to teach families how to collect nasal and stool samples and do temperature readings of their babies. They also collect milk from breastfeeding mothers. 

The impact of breast milk on developing autoimmune systems has been the focus of Morrow’s research for decades.   

titus

Megan White, with her son, Titus, the second her children to be enrolled in research studies on vaccinations.

“Human milk has a major role in protection against respiratory and gastrointestinal infections of infancy,” she says. “Protection involves both acquired and innate immune systems, including maternal antibodies, complement, innate defense proteins, and oligosaccharides.”

Titus the charmer doesn’t know big words like “oligosaccharides,” but he did get a lot of fawning “oohs” and “ahhs” from the Fab 5 when they gathered in the sun-drenched lobby of the Clinical Sciences Pavilion here.

Titus and his 5-year-old sister, Alyssia, are sure to be long-time contributors to vaccine science and the ongoing work of the Fab 5. 

Their mom, Megan White, will make sure of that. 

“To me it is important to be a part of Dr. Staat’s research because we are living in a time when parents are refusing to give their children vaccinations,” she explains. “There are always constant changes in viruses and making sure that the vaccine is still effective and safe puts a lot of parents at ease.”

Wisdom, not just as a mom, but as someone who works in Outpatient Registration at Cincinnati Children’s.