Scientists at the Cornell College of Veterinary Medicine (CVM) have found that administering a rotavirus vaccine to newborn mice via a shot, rather than an oral dose, increases its efficacy, particularly for at-risk newborns.
"This is especially important for infants in low- and middle-income countries, where the current rotavirus vaccine doesn't work as well," said Dr. Sarah Caddy, assistant professor with the Baker Institute for Animal Health and the Department of Microbiology and Immunology. Caddy and her team explored why the oral liquid rotavirus vaccine did not work very well in these infants, and examined alternative vaccination methods. This research published Oct. 14 in the EMBO Journal.
Rotavirus can cause life-threatening diarrhea and vomiting in children younger than 5. Currently, babies are given an oral vaccine to prevent severe gastrointestinal symptoms caused by rotavirus. However, its efficacy is often less than 50% in lower-income countries. While many factors likely contribute to this poor efficacy, Caddy's team has shown that maternal antibodies are an important negative influence.
Maternal antibodies are protective proteins transferred from mother to baby during pregnancy and breastfeeding, and are present in higher concentrations in newborns in lower income countries where mothers are exposed to higher levels of infection. While they might be an evolutionary strategy to protect immunologically naïve newborns from pathogens in the environment, they can also block vaccine efficacy - as is the case with the rotavirus vaccine.
Why maternal antibodies have this effect has puzzled researchers.
"Previously, it wasn't fully understood how maternal antibodies block the rotavirus vaccine from working properly," Caddy said.
To unravel this mystery, her team developed a mouse model to mimic the same mechanisms as human mothers and infants during rotavirus infection and vaccination. Just like humans, when these newborn mice had maternal antibodies, even in very low numbers, the newborns failed to produce their own antibodies to the rotavirus vaccine.
"We found that the maternal antibodies were removing the vaccine particles from the body," Caddy said. But where and how remained unclear.
Because the rotavirus vaccine is given orally, Caddy's team hypothesized that the newborns' gut was the scene of the crime. After testing the vaccinated newborns' stool, their theory was confirmed.
"Our findings suggest that the maternal antibodies in the intestines are binding to the vaccine particles and essentially 'protecting' the infants from the vaccine," Caddy said.
To overcome this interference, Caddy's group tested different vaccine strategies. They found that when the vaccine was delivered by injection instead of by mouth, maternal antibodies in the pups had a less negative impact on the pup's immune responses.
"These findings are important because they help explain why the current vaccine may not work well in infants with high levels of maternal antibodies," Caddy said. "We think this research can guide future vaccine designs that work better for newborns around the world."
Financial support was provided by the Wellcome Trust Clinical Research Career Development Fellowship, and by the Baker Institute.
Lauren Cahoon Roberts is director of communications at the College of Veterinary Medicine.
