Last updated February 22, 2018 at 2:36 pm
Australian discovery closes a crucial age-gap during which existing vaccines left very young children unprotected.
Nurse giving newborn baby Rotavirus vaccine immunisation. It protects children from rotaviruses, which are the leading cause of severe diarrhea among infants and young children but can only be administered after six weeks of age. Credit: iStock
Rotavirus infection induces severe gastroenteritis and is responsible for about 37 per cent of childhood deaths caused by diarrhoea. It accounts for more that 200,000 deaths worldwide every year.
The condition is caused by any one of eight species of double-stranded RNA virus clustered in a single genus of the family Reoviridae, although one, Rotavirus A, accounts for roughly 90 per cent of the total.
Currently there are two rotavirus vaccines used in many countries – in Australia, they are known as Rotarix and RotaTeq. Both have been available since 2006 and have delivered very large reductions in gastroenteritis hospitalisations for young children.
Both, however, can only be administered to children at six weeks or beyond, leaving younger babies unprotected.
A team from the Murdoch Children’s Research Institute (MCRI) in Parkville, Victoria, has now solved that problem, developing a new vaccine, dubbed RV3-BB, that is designed to be administered orally in three stages, the first occurring just hours after birth.
In a paper published in the New England Journal of Medicine (NEJM), the team, led by University of Melbourne gastroenterologist Julie Bines, reports the results of the first clinical trial of the treatment, conducted using 1513 children in Indonesia.
The participants were divided into three cohorts. The first, used as a control, received a placebo treatment. The second received “neonatal-schedule” doses at zero-to-five days, eight weeks and 14 weeks. The third received an “infant-schedule”, with doses at eight, 14 and 18 weeks.
The researchers then monitored gastroenteritis cases among the children until the age of 18 months. In the placebo cohort, 5.6 per cent got sick at least once. In the infant schedule group, the rate was 2.7 per cent, and in the neonate group it was just 1.4.
In the NEJM paper, Bines and her colleagues report that 94 per cent of kids in the neonate group were protected from rotavirus for the first year of life, and 75 per cent were still protected at 18 months.
The key ingredient in RV3-BB is a modified version of a human rotavirus strain sometimes found in newborns, called RV3.
As early as 1983, it was noted that opportunistic infection of babies by RV3 seemed to confer immunity against more virulent types of rotavirus for up to three years.
Bines and her team note that RV3 “appears to be naturally attenuated and adapted to the newborn gut; it has been shown to replicate effectively despite the presence of maternal antibodies and despite the baby being breast-fed”.
After an earlier safety trial in New Zealand using a modified form of the virus revealed no safety concerns, the decision was made to scale up operations and launch a full-scale clinical trial.
The results are extremely encouraging. Being able to administer the vaccine straight after birth offers not only boosts protection, but also overcomes a significant obstacle to vaccination that occurs all too often in poorer countries.
“In low resource settings, birth offers the best opportunity for contact between mother, baby and health services,” says Bines. “RV3-BB provides an ideal vaccination opportunity.”
The development of the virus by MCRI is particularly apt. In 1973, it was another team from the institution, led by Ruth Bishop, that identified rotavirus as the cause of severe dehydrating diarrhoea, thus opening a path towards successful prevention.
The research is published in the New England Journal of Medicine.
