Safety and immunogenicity of human neonatal RV3 rotavirus vaccine (Bio Farma) in adults, children, and neonates in Indonesia: Phase I Trial

Vaccine. 2021 Jul 30;39(33):4651-4658. doi: 10.1016/j.vaccine.2021.06.071. Epub 2021 Jul 6.

Abstract

Background: Despite safe and effective WHO prequalified rotavirus vaccines, at least 84 million children remain unvaccinated. A birth dose schedule of the RV3-BB vaccine was reported to be highly efficacious against severe rotavirus disease in Indonesian infants and is under further development at PT Bio Farma, Indonesia. The aim is to develop a rotavirus vaccine starting from birth that could improve the implementation, safety, and effectiveness of vaccines.

Methods: A multi-site phase I study of a human neonatal RV3 rotavirus vaccine (Bio Farma) in adults, children, neonates in Indonesia from April 2018 to March 2019. The adult and child cohorts were open-labeled single-dose, while the neonatal cohort was randomized, double-blind, and placebo-controlled three-doses at the age of 0-5 days, 8-10 weeks, and 12-14 weeks. The primary objective was to assess the safety of vaccines with the immunogenicity and vaccine virus fecal shedding as the secondary endpoints in neonates.

Results: Twenty-five adults, 25 children, and 50 neonates were recruited, and all but one in the neonatal cohort completed all study procedures. Three serious adverse events were reported (1 adult & 2 neonates), but none were assessed related to investigational product (IP). The neonatal vaccine group had a significantly higher positive immune response (cumulative seroconverted SNA and IgA) 28 days after three doses than those in the placebo group (72% vs. 16.7%, respectively). The GMT of serum IgA in the vaccine group was significantly higher at post IP dose 1 (p < 0.05) and post IP dose 3 (p < 0.001) compared to the placebo group.

Conclusion: The trial results show that the RV3 rotavirus vaccine (Bio Farma) is well tolerated in all participant cohorts (adults, children, and neonates). Three doses of this vaccine administered in a neonatal schedule were immunogenic. These promising results support further clinical development of the RV3 rotavirus vaccine (Bio Farma).

Keywords: Diarrhea; RV3; Rotavirus; Rotavirus vaccine.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral
  • Child
  • Double-Blind Method
  • Humans
  • Immunogenicity, Vaccine
  • Indonesia
  • Infant
  • Infant, Newborn
  • Rotavirus Infections* / prevention & control
  • Rotavirus Vaccines* / adverse effects
  • Rotavirus*
  • Vaccines, Attenuated / adverse effects

Substances

  • Antibodies, Viral
  • RV3 rotavirus vaccine
  • Rotavirus Vaccines
  • Vaccines, Attenuated