Molecular characterisation of rotavirus strains detected during a clinical trial of the human neonatal rotavirus vaccine (RV3-BB) in Indonesia

Daniel Cowley,Hera Nirwati,Celeste M Donato,Nada Bogdanovic-Sakran,Karen Boniface,Carl D Kirkwood,Julie E Bines

doi:10.1016/j.vaccine.2018.08.027

Abstract

BackgroundThe RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth. The aim of the current study was to characterise the rotavirus strains causing gastroenteritis during the Indonesian Phase IIb efficacy trial. MethodsA randomized, double-blind placebo-controlled trial involving 1649 participants was conducted from January 2013 to July 2016 in Central Java and Yogyakarta, Indonesia. Participants received three doses of oral RV3-BB vaccine with the first dose given at 0–5 days after birth (neonatal schedule), or the first dose given at ∼8 weeks after birth (infant schedule), or placebo (placebo schedule). Stool samples from episodes of gastroenteritis were tested for rotavirus using EIA testing, positive samples were genotyped by RT-PCR. Full genome sequencing was performed on two representative rotavirus strains. ResultsThere were 1110 episodes of acute gastroenteritis of any severity, 105 episodes were confirmed as rotavirus gastroenteritis by EIA testing. The most common genotype identified was G3P[8] (90/105), the majority (52/56) of severe (Vesikari score ≥11) rotavirus gastroenteritis episodes were due to the G3P[8] strain. Full genome analysis of two representative G3P[8] samples demonstrated the strain was an inter-genogroup reassortant, containing an equine-like G3 VP7, P[8] VP4 and a genogroup 2 backbone I2-R2-C2-M2-A2-N2-T2-E2-H2. The complete genome of the Indonesian equine-like G3P[8] strain demonstrated highest genetic identity to G3P[8] strains circulating in Hungary and Spain. ConclusionsThe dominant circulating strain during the Indonesian Phase IIb efficacy trial of the RV3-BB vaccine was an equine-like G3P[8] strain. The equine-like G3P[8] strain is an emerging cause of severe gastroenteritis in Indonesia and in other regions.

Highlights

Rotavirus is the most common cause of severe gastroenteritis in children under five years of age [1]
A randomized, placebo-controlled trial to evaluate the efficacy of an oral human-strain neonatal rotavirus vaccine (RV3-BB) was recently completed in central Java and Yogyakarta, Indonesia [8]
The analysis of vaccine efficacy was performed on per protocol (n = 1513) and intention to treat (ITT) (n = 1649) populations followed for severe episodes of rotavirus gastroenteritis occurring from two weeks post investigational product (IP) dose 4 to 18 months of age [8]

Summary

Introduction

Rotavirus is the most common cause of severe gastroenteritis in children under five years of age [1]. The currently available rotavirus vaccines have been introduced into the national immunisation programs of 92 countries globally and reduced hospital admissions and child mortality from gastroenteritis [2,3,4,5]. Despite this success, several barriers to global vaccine implementation exist, including cost and sub-optimal efficacy in low-income. A randomized, placebo-controlled trial to evaluate the efficacy of an oral human-strain neonatal rotavirus vaccine (RV3-BB) was recently completed in central Java and Yogyakarta, Indonesia [8].

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