CU Anschutz and Children’s Hospital Colorado lead national pandemic response project

Researchers are working to better prepare for the next pandemic.

One of those researchers is Kevin Messacar, MD, PhD, an infectious disease expert and physician at Children’s Hospital Colorado and associate professor at the University of Colorado Anschutz Medical Campus. Messacar is leading an innovative, nationwide pilot study focusing on enterovirus D68, a virus that is linked to a rare polio-like illness in children called Acute Flaccid Myelitis (AFM).

The Enterovirus D68 (EV-D68) Pilot Study is part of the Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) program, an initiative of the National Institutes of Allergy and Infectious Diseases (NIAID) Vaccine Research Center.

“The COVID-19 pandemic is not likely to be the last pandemic we see in our lifetime,” says Dr. Messacar. “PREMISE is our attempt to be forward-looking by using disease surveillance to create ‘on the shelf tools’ so that when the next pathogen emerges, we will be ready.”

Scientists will analyze blood and respiratory specimens to monitor participants’ exposure and responses to emerging pathogens. Their goal is to develop diagnostic, therapeutic and preventive tools that may be used to combat future pandemics.

CU Anschutz is the central site of the pilot study, which is funded with the help of a nearly $2 million subcontract* with the National Institutes of Health-funded Frederick National Laboratory for Cancer Research operated by Leidos Biomedical Research, Inc.

Children and families enrolled in the study voluntarily provide two blood specimens pre- and post-enterovirus D68 (EV-D68) season. Parents can also elect to fill out symptom surveys every few weeks during EV-D68 season, and if participants get sick, they can provide a nasal specimen.

“We are seeking the buy-in from families interested in helping us combat the next pandemic,” Messacar says. “The response so far has been overwhelmingly positive. I have been blown away by our families’ willingness to contribute to the greater good and to science.”

The PREMISE EV-D68 pilot study aims to enroll five hundred children, 10-years-old or younger, over a three-year period. Once enrolled, each cohort of children will be followed for 18 months. It is a logistically challenging study—and something that speaks to the depth and breadth of expertise and resources on the CU Anschutz Medical Campus, including Children’s Hospital Colorado and the Colorado Clinical and Translational Sciences Institute (CCTSI).

Specialized research nurses from the CCTSI work with the families to collect the specimens, which must then be transported across campus for same-day processing in the Adriana Weinberg Lab in Infectious Diseases. At that point, the samples are processed, preserved in liquid nitrogen and flown to the NIAID Vaccine Research Center in Bethesda, Maryland. Analyses of the specimens will reveal the pathogens to which a child was exposed, and how their body responded to the pathogens.

Messacar says the primary aim is to inform the development of countermeasures against the next emerging pathogen: tests, treatments and vaccines. Key to being able to effectively develop these, however, is understanding epidemiology of pathogens. At what ages are children being exposed to which pathogens? How are emerging pathogens circulating in the population from year to year?

“We have expert physician scientists, research nurses, specialized lab processing capabilities, study coordinators, regulatory, grants and contracting specialists. What we have shown is that Children’s Hospital Colorado and the University of Colorado have the capability to be the coordinating central site for this type of multicenter research that drives the science forward. I feel fortunate to be here,” Messacar says.

Previous studies on AFM have enabled researchers to do the basic science work to develop a monoclonal antibody treatment candidate for EV-D68. And there are some EV-D68 vaccine candidates, but they are still in the early phases of laboratory studies. Messacar says there is still so much work to do.

“We don’t understand the age children are first exposed to and infected by EV-D68. We want to know when maternal immune protection for a baby goes away and when first natural infection happens; that is when you would want to immunize. We still lack much of that data,” Messacar says.

Polio is the closest relative to AFM. Historical patterns of polio show it circulated in regular patterns at lower levels, like AFM, prior to rapidly increasing in prevalence in the 1950s. “History has taught us that we can’t predict what is going to happen with emerging infectious diseases,” says Messacar. “COVID has taught us that instead of trying to predict, we should prepare.”

The University of North Carolina at Chapel Hill, Weill Cornell Medical College and Princeton University will also be involved along with the NIAID Vaccine Research Center. For more information on how to participate in the PREMISE pilot study, email PREMISEResearchStudy@childrenscolorado.org.