We are proud to announce a third publication coming from our rotavirus vaccine project, funded by the Bill & Melinda Gates Foundation. The peer-reviewed journal Human Vaccines & Immunotherapeutics has published scientific data generated together with the University of Kansas on the formulation development of a live-attenuated, human neonatal rotavirus vaccine candidate (RV3-BB).
The three main objectives to facilitate use in low- and middle- income countries include (1) a liquid, 2–8°C stable vaccine, (2) no necessity for pre-neutralization of gastric acid prior to oral administration of a small-volume dose, and (3) a low-cost vaccine dosage form.
The development of a stable liquid formulation of a live, attenuated viral vaccine can be challenging due to the inherent instability of live viruses and variability observed in viral infectivity assays (FFA). To overcome this assay variability, in addition to the FFA method, an experimental viral infectivity qPCR assay was developed to assess initial short-term accelerated stability data for candidate RV3-BB liquid formulations.
The qPCR assay enabled more rapid comprehensive formulation development in terms of monitoring RV3-BB stability profiles. A wide variety of different classes and types of pharmaceutical excipients were screened for their ability to stabilize RV3-BB during exposure to elevated temperatures, freeze-thaw and agitation stresses.
Several optimized RV3-BB candidate formulations were identified based on negligible viral infectivity losses during storage at 2–8°C and −20°C for up to 12 months, as well as by relative stability comparisons at 15°C and 25°C (up to 12 and 3 months, respectively).
About the live-attenuated rotavirus vaccine RV3-BB
The RV3-BB human neonatal rotavirus vaccine was developed at the Murdoch Children’s Research Institute. The live-attenuated vaccine candidate provides protection from severe rotavirus disease from birth. Due to an earlier peak age of disease in high-mortality settings, the vaccine is tested in a neonatal schedule. In a recent randomized placebo-controlled efficacy study conducted in Central Java and Yogyakarta, Indonesia, three doses of RV3-BB in Indonesian infants resulted in 75% efficacy against severe rotavirus gastroenteritis in the first 18 months of life when administered in a neonatal schedule. This is a significantly higher efficacy than that seen with currently marketed rotavirus vaccines.
This project was funded by a grant from the Bill & Melinda Gates Foundation (#OPP1148427) aimed to accelerate the development of a low-cost, liquid RV3-BB rotavirus vaccine for Gavi-eligible countries through formulation development and bulk process optimization.
Link to full article.