The University of Virginia School of Medicine is leading a study to determine why vaccines that work so well on children in the developed world don’t work nearly so well for children in poorer countries.
Oral vaccines for paralytic polio and life-threatening rotavirus have been a miracle of modern medicine for millions of children around the globe; yet these same vaccines aren’t always protecting thousands of children in poor and less developed countries – and scientists don’t know why. One key to solving this challenge lies in understanding what’s different in the biological makeup of children whose bodies reject the protection they so desperately need from these diseases. Thanks to a $14.7 million grant from the Bill & Melinda Gates Foundation, scientists at the University of Virginia now have the opportunity to investigate why oral vaccines fail in the very children who need them the most.
The PROVIDE (Performance of Rotavirus and Oral polio Vaccines In Developing countries) study is co-led by William A. Petri Jr., MD, from the University of Virginia and Beth Kirkpatrick, MD, from the University of Vermont. They are working with an international team of investigators to understand the spectrum of biologic reasons for failure of the oral vaccines for polio and rotavirus.
“The average child who contracts paralytic polio in India has received more than the four recommended doses of the oral polio vaccine,” explains Petri, citing a 2007 study published in Lancet. “Similarly, the new and life-saving vaccine against rotavirus is only half as effective in Bangladesh as it is in the United States.”
Nearly 1000 infants in the first month of life will be enrolled in this study: 700 children at the International Centre for Diarrheal Disease Research, Bangladesh (ICDDR, B) in Dhaka and 300 children at the National Institute of Cholera and Enteric Diseases (NICED) in Kolkata, India.
Researchers will be investigating their hypothesis: that chronic intestinal inflammation and damage from enteric infections leads to a selective defect in a child’s response to oral vaccines. To test this theory, UVA scientists will determine if children who fail oral vaccination have more episodes of diarrhea, or are more malnourished, than children with a normal vaccine response. They also will measure the role of the intestinal bacterial flora or microbiome, and the impact of intestinal damage on the nature of the immune response to vaccination (antibody or cell mediated responses). Tests will be conducted in collaboration with the laboratories of Jeffrey Gordon, MD, of Washington University and Mark Davis, PhD, of Stanford University.
Results from this study could lead to targeted interventions to prevent oral vaccine failure, such as the use of injected vaccines to boost oral vaccination and the prevention or treatment of intestinal barrier disruption.
Expert international collaborators (Dr. Rashidul Haque, Dr. Firdausi Qadri, Dr. Cecil Czerkinsky and Dr. Dipika Sur) will be integrally involved in the field for these studies. Program and database management analyses will be directed by Dr. Josyf Mychaleckyj along with Drs. Uma Nayak and Cynthia Snider at the University of Virginia.
