A new oral rotavirus vaccine administered within the first few days of life appears effective against severe rotavirus gastroenteritis in newborns, a study has found.

Julie E. Bines, MD, from the RV3 Rotavirus Vaccine Program at the Murdoch Children’s Research Institute in Melbourne, and her coauthors reported the results of a double-blind, placebo-controlled phase 2b trial in 1,513 healthy newborns in Indonesia. Participants were randomized to three doses of oral human neonatal rotavirus vaccine either on a neonatal schedule (0-5 days, 8-10 weeks, and 14-16 weeks of age) or an infant schedule (8-10 weeks, 14-16 weeks, and 18-20 weeks of age), or the equivalent schedules of placebo.

When all three doses were administered, vaccine efficacy with the neonatal schedule was 75% by 18 months of age (P less than .001), while the efficacy of the infant schedule at 18 months was 51% (P = .03), and in the two groups combined, the efficacy was 63% (P less than .001) in the per-protocol analysis, the researchers reported in the New England Journal of Medicine. The results were similar in the intention-to-treat analysis.

At 12 months of age, the rotavirus vaccine showed an efficacy of 94% in participants who received all three doses of the neonatal schedule. That efficacy was 77% in those who received the doses on the infant schedule.

Overall, severe rotavirus gastroenteritis was reported in 5.6% of the placebo group, compared with 2.1% of the combined vaccine group. The time from randomization to first episode of gastroenteritis was significantly longer among participants who received the vaccine, compared with those who received placebo.

“The use of a neonatal dose was investigated in the early phase of development of the rotavirus vaccine but was not pursued because of concerns regarding inadequate immune responses and safety,” wrote Dr. Bines and her associates

They noted that the results of this trial compared favorably with the efficacy of licensed vaccines in similar low-income countries that experienced a high burden of rotavirus disease.

The rates of severe adverse events were similar across all the trial groups. There were no episodes of intussusception seen within the 21-day risk period after immunization, either in the vaccine or placebo groups. However, there was one episode of intussusception in a child on the infant schedule group, which occurred 114 days after the third dose of the vaccine.

“Because intussusception is rare in newborns, the administration of a rotavirus vaccine at the time of birth may offer a safety advantage,” Dr. Bines and her associates said.

The study was supported by the Bill and Melinda Gates Foundation, the National Health and Medical Research Council, PT Bio Farma, and the Victorian government’s Operational Infrastructure Support Program. Authors declared fees, grants, and institutional support from the study sponsors, and three authors also declared a stake in the patent of the RV3-BB vaccine , which is licensed to PT Bio Farma.

SOURCE: Bines JE et al. N Engl J Med. 2018;378:719-30.