A multidisciplinary team of Yale scientists has received a $4 million federal grant to study the effectiveness of a new vaccine and monoclonal antibody shot designed to prevent respiratory syncytial virus (RSV) in infants.
The five-year grant from the National Institutes of Health will allow the researchers to investigate the interventions’:
- overall effectiveness
- durability in providing immunity
- effectiveness against different virus lineages
- effectiveness across age groups
Globally, RSV is second only to malaria as the leading cause of infant death. It is estimated that over 100,000 children under 5 die from RSV annually, half of them infants less than 6 months of age. In the United States, RSV is associated with 1.5 million annual medical encounters in children less than 5 years old and is the leading cause of hospitalization among infants under 1 year. It is the most common form of bronchitis and pneumonia among infants.
After years of trials and study, the U.S. Food and Drug Administration and the U.S. Centers for Disease Control and Prevention approved the use of two new tools to help protect infants from RSV in 2023. Nirsevimab, a long-acting monoclonal antibody, is the first drug of its kind to be used as part of a routine immunization program for infants. Abrysvo is the first vaccine to be specifically labeled for use in pregnant women to protect their infants from RSV disease
“The … introduction of new immunoprophylactic agents offers unique opportunities to confront the challenge of RSV in infants,” the researchers said in their project summary. “As is the case with any new vaccine, it will be important to conduct studies during the early phases of implementing these new immunization strategies to answer many unanswered questions surrounding their risks and benefits in real-world settings.”
Data collected in the study will inform health officials and policymakers on the optimal use of the new RSV preventative strategies and will help build public confidence in the immunization program, the researchers said.
The research team includes specialists in a variety of disciplines — vaccinology, clinical epidemiology, pediatric infectious diseases, viral genomics, bioinformatics, and translational immunology. A distinct feature of the project is that it will utilize a “vaccinomics” framework to study interactions between the virus, the vaccines, and the mother/child immune system. The researchers believe this approach will generate novel mechanistic data that will advance our understanding of the various factors that may contribute to diminished or maladaptive vaccine responses.
Carlos R. Oliveira, MD, PhD, an attending physician and specialist in pediatric infectious diseases at Yale New Haven’s Children Hospital, is principal investigator. Oliveira is an assistant professor of pediatrics (infectious diseases and global health), of biostatistics (health informatics), and of biomedical informatics & data science at both Yale School of Medicine (YSM) and the Yale School of Public Health (YSPH).
YSPH co-investigators on the project are Professor of Epidemiology of Microbial Diseases Linda Niccolai, PhD, Associate Professor of Epidemiology of Microbial Diseases Nathan Grubaugh, PhD, and Associate Professor of Epidemiology of Microbial Diseases Daniel Weinberger, PhD. Eugene Shapiro, MD, professor of pediatrics, of epidemiology, and of investigative medicine at both YSM and YSPH, is also a co-investigator along with Paul Aronson, MD, associate professor of pediatrics (emergency medicine), and Carrie Lucas, PhD, associate professor of immunobiology, both of YSM.
With the NIH funding, the research team plans to conduct a large-scale case-controlled study using data collected from an estimated 3,750 children one year of age or younger who receive care for acute respiratory illness at inpatient and outpatient clinical sites of the Yale New Haven Health System, the largest and most comprehensive health care system in Connecticut.
Data will be collected from multiple sources including health records, interviews, immunization registries, and population surveys. Investigators will also conduct genetic characterization of all RSV viruses identified in the study, monitor the genetic diversity of the virus over time, and quantify the relative effectiveness of the immunizations against various viral lineages.