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N Engl J Med. 2018 Feb 22;378(8):719-730. doi: 10.1056/NEJMoa1706804.

Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth.

Author information

1
From the RV3 Rotavirus Vaccine Program, Murdoch Children's Research Institute (J.E.B., A.H., E.W., D.C., J.S., F.J., G.B., K.J.L., G.L.B., K.B., N.B.-S., D.P., R.F.B., C.D.K., J.P.B.), the Department of Paediatrics, University of Melbourne (J.E.B., D.C., K.J.L., G.L.B., R.F.B., C.D.K., J.P.B.), and the Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital Melbourne (J.E.B., J.S.), Parkville, the Departments of Paediatrics and of Epidemiology and Preventive Medicine, Monash University, and the Department of Infection and Immunity, Monash Children's Hospital, Clayton (J.P.B.), and Medicines Development for Global Health (A.H.) and Global BioSolutions (J.A.), Melbourne - all in Victoria, Australia; the Department of Pharmacology and Therapy (J.A.T.), the Pediatric Research Office, Department of Paediatrics (C.D.S., A.V.I., Y.S.), and the Department of Microbiology (H.N.), Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, and PT Bio Farma, Bandung (N.S.B.) - all in Indonesia; and the Bill and Melinda Gates Foundation, Seattle (C.D.K.).

Abstract

BACKGROUND:

A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine.

METHODS:

We conducted a randomized, double-blind, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) in preventing rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB, administered according to a neonatal schedule (0 to 5 days, 8 weeks, and 14 weeks of age) or an infant schedule (8 weeks, 14 weeks, and 18 weeks of age), or placebo. The primary analysis was conducted in the per-protocol population, which included only participants who received all four doses of vaccine or placebo within the visit windows, with secondary analyses performed in the intention-to-treat population, which included all participants who underwent randomization.

RESULTS:

Among the 1513 participants in the per-protocol population, severe rotavirus gastroenteritis occurred up to the age of 18 months in 5.6% of the participants in the placebo group (28 of 504 babies), in 1.4% in the neonatal-schedule vaccine group (7 of 498), and in 2.7% in the infant-schedule vaccine group (14 of 511). This resulted in a vaccine efficacy of 75% (95% confidence interval [CI], 44 to 91) in the neonatal-schedule group (P<0.001), 51% (95% CI, 7 to 76) in the infant-schedule group (P=0.03), and 63% (95% CI, 34 to 80) in the neonatal-schedule and infant-schedule groups combined (combined vaccine group) (P<0.001). Similar results were observed in the intention-to-treat analysis (1649 participants); the vaccine efficacy was 68% (95% CI, 35 to 86) in the neonatal-schedule group (P=0.001), 52% (95% CI, 11 to 76) in the infant-schedule group (P=0.02), and 60% (95% CI, 31 to 76) in the combined vaccine group (P<0.001). Vaccine response, as evidenced by serum immune response or shedding of RV3-BB in the stool, occurred in 78 of 83 participants (94%) in the neonatal-schedule group and in 83 of 84 participants (99%) in the infant-schedule group. The incidence of adverse events was similar across the groups. No episodes of intussusception occurred within the 21-day risk period after administration of any dose of vaccine or placebo, and one episode of intussusception occurred 114 days after the third dose of vaccine in the infant-schedule group.

CONCLUSIONS:

RV3-BB was efficacious in preventing severe rotavirus gastroenteritis when administered according to a neonatal or an infant schedule in Indonesia. (Funded by the Bill and Melinda Gates Foundation and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612001282875 .).

PMID:
29466164
PMCID:
PMC5774175
DOI:
10.1056/NEJMoa1706804
[Indexed for MEDLINE]
Free PMC Article

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