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

Abstract

BackgroundA birth dose strategy using a neonatal rotavirus vaccine to target early prevention of rotavirus disease may address remaining barriers to global vaccine implementation.MethodsWe conducted a randomized, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) to prevent rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB administered in a neonatal schedule at 0-5 days, 8 and 14 weeks or infant schedule at 8, 14 and 18 weeks, or placebo. Laboratory-confirmed rotavirus gastroenteritis was graded using a modified Vesikari score. The primary analysis was efficacy against severe rotavirus gastroenteritis from two weeks after all doses to 18 months in the combined vaccine group (neonatal and infant schedule) compared with placebo.ResultsVaccine efficacy against severe rotavirus gastroenteritis to 18 months was 63% in the combined vaccine group (95% CI 34, 80; p<0.001), 75% in the neonatal vaccine group (95% confidence interval [CI] 44, 91; p<0.001) and 51% in the infant vaccine group (95% CI 7, 76; p=0.03) in the per protocol analysis, with similar results in the intention-to-treat analysis. Vaccine efficacy to 12 months was 94% in the neonatal vaccine group (95%CI 56, 99; p=0.006). Vaccine take occurred in 78/83 (94%) in the neonatal vaccine group and 83/84 (99%) in the infant vaccine group. The vaccine was well tolerated, with similar incidence of adverse events in vaccine and placebo recipients.ConclusionRV3-BB was efficacious, immunogenic and well-tolerated when administered in a neonatal or infant schedule in Indonesia.

The art of partnerships for vaccines

“…Despite the good safety profile of four WHO PQ live attenuated oral rotavirus vaccines, 90 million children worldwide still lack access [11], and intussusception and lower efficacy remain a concern in some countries. Biofarma is developing a G3P [6] strain oral vaccine with 3-dose schedule, showing excellent protection against rotavirus gastroenteritis [12]. Injectable non-replicating vaccines may improve the safety and efficacy and could be used in combination vaccines.…”

Rotavirus vaccine for neonates

“…When administered on a neonatal dosing schedule, RV3‐BB had a vaccine efficacy of 94% at 12 months of age and 75% at 18 months of age. RV3‐BB administered on both the neonatal and infant schedules demonstrated comparable or superior efficacy to other rotavirus vaccines in low‐income countries . While the trial was underpowered to detect rare adverse events, no cases of intussusception were detected within 21 days of vaccine administration.…”

“…Rotavirus is a leading cause of morbidity and mortality for neonates and children. Worldwide, over 200 000 children die from rotavirus gastroenteritis each year and more than 90 million infants still lack access to a rotavirus vaccine . Traditional vaccine schedules administer doses at 8, 14 and 18 weeks of age.…”

“…Dosing at birth is likely to be efficacious and safe: RV3‐BB P[6] vaccine strains effectively adhere to the newborn gut , display minimal interference from maternal breast milk and are naturally attenuated . This strain also provides heterotypic serologic responses, which may offer cross‐protection against other circulating rotavirus strains . Further potential advantages of a neonatal schedule include improved uptake, particularly in low‐income countries.…”

Clinicians should remain vigilant for biliary atresia as early diagnosis and surgery are vital

“…There is important information in Lee et al's study that can help to plan future studies on strategies to reduce the risk of BA variants, at the very least. We need to understand the exact timing of the initial BA injury and carry out studies when neonatal vaccination starts earlier . Mothers vaccinated during pregnancy need to be studied, in common with other infections and the rotavirus BA murine model …”