Benjamin Lee, M.D., UVM Assistant Professor of Pediatrics. (Photo: UVM COM Design & Photography)
University of Vermont researcher Benjamin Lee, M.D., is studying whether a higher dose will help make the rotavirus vaccine more effective in developing countries, where the disease causes more than 200,000 children’s deaths each year due to related dehydration. The vaccine has had less success preventing the diarrheal disease in these areas than in the United States and other wealthier nations.
“There are a lot of proposed reasons why that occurs, but nobody knows for sure,” says Lee, an assistant professor of pediatrics at UVM Children’s Hospital and investigator in the UVM Vaccine Testing Center.
Rotavirus infects the gastrointestinal system and remains the most common cause of diarrheal disease in the developing world. In the U.S., babies aged two to six months have received the vaccine since 2006, greatly reducing infection rates.
Lee’s receipt of a $150,000 Child Health Research Award from the Charles H. Hood Foundation – effective July 1 – will support a study in Bangladesh targeting 220 infants. Half of the participants will be randomly selected to receive the standard rotavirus vaccine dose used in the U.S., while the other half will receive a higher dose of the vaccine.
In Bangladesh and other countries, mostly in southern Asia and Africa, lab tests used to determine the immune system’s response to the vaccine have been poor indicators of how well children actually were protected from rotavirus as they got older, Lee says. That problem has confounded researchers, as well.
His study will use two primary measures for response to the higher-dose vaccine. First, researchers will look for more shedding of the virus into the children’s stools after they get inoculated. “That would indicate the vaccine is replicating in the gut the way it’s supposed to, to create a good immune response,” Lee says.
They also will look at the development of antibodies to indicate a strong immune response, as well as other markers of immunogenicity to help overcome the inaccuracy of previous lab tests, Lee says.
Those measures will only suggest that the higher-dose vaccine works better than the standard dose in protecting the children down the road. To know with certainty, researchers will have to conduct a full-scale efficacy trial, following the study participants over time, which will require additional funding, Lee says.
The Vaccine Testing Center was part of an academic team, including the University of Virginia and the International Centre for Diarrhoeal Disease Research in Bangladesh, which previously studied the problems with rotavirus vaccines administered in low-income countries. Under a $2.2 million grant from the Bill and Melinda Gates Foundation, UVM researchers are now conducting follow-up studies using samples from 700 previously immunized Bangladeshi children to develop a better lab test for efficacy.
Vaccines use weakened versions of live virus or bacteria to train the body’s immune system to recognize and fight the infection. One suspicion is that mothers in the developing world pass down antibodies to their infants through breast milk or in utero that are particularly successful at attacking and eradicating the vaccine-introduced virus, preventing it from replicating enough to trigger the immune response. That leaves those children more vulnerable later to a full-blown infection, Lee says.
Differences in the microbiome or pathogen levels in the gut, perhaps more inflammation, also might interfere with the ability to respond to the vaccine. Gastrointestinal infections are particularly difficult to figure out, Lee says.
“If we are also able to understand why and gain a better understanding of the immune response to pathogens in the gut, then that would be a big advance not only for rotavirus, but for other diseases as well,” he says.