Rotavirus gastroenteritis continues to be a major cause of illness in children less than 5 years of age worldwide. Of the estimated 215,000 deaths due to rotavirus gastroenteritis each year, more than 90% occur in low-income countries in Africa and Asia. Rotavirus diarrhoea results in millions of hospitalisations and clinic visits, placing a significant burden on the healthcare system and families.
The RV3-BB vaccine is the culmination of over four decades of research in Australia by the Murdoch Children's Research Institute, The Royal Children's Hospital Melbourne and the University of Melbourne, following the discovery of rotavirus by a team led by Professor Ruth Bishop in 1973.
The Rotavirus group’s research focuses on the development of a low cost human neonatal rotavirus vaccine (RV3-BB). After completion of Phase I and II trials in Australia New Zealand and Indonesia the team have demonstrated proof of principle that the vaccine is immunogenic and well tolerated in neonates and infants.
Rotavirus (pictured above) was discovered by a team led by Professor Ruth Bishop AO in 1973
Development of a low cost oral Rotavirus vaccine (RV3-BB)
The Rotavirus research team aims to develop a low cost oral rotavirus vaccine administered at birth.A novel human neonatal vaccine developed in Melbourne (RV3-BB) has been shown to be safe and immunogenic in Phase I and II studies in newborns and infants conducted in Australia, New Zealand and Indonesia. Currently the team is preparing for a Phase II study to be conducted in Malawi, Africa.
Phase II dose ranging study of RV3-BB in Malawi
This Phase II study to be conducted in and around Blantyre district, Malawi will determine the optimal vaccine titre of the vaccine required to elicit an immune response. The RV3-BB vaccine will be assed at three different vaccine titres using a birth dose schedule of the vaccine. In addition an infant schedule will also be tested in a high disease burden area of Africa. Currently over 50% of deaths due to rotavirus gastroenteritis occur in Sub-Saharan Africa. Barriers to vaccine implementation exist, such as cost, and supply, in addition a lack of efficacy in high burden areas will continue to impact the full promise of the current vaccines. This study will determine if a lower titre, resulting in a lower cost vaccine will be immunogenic and will inform vaccine manufacture.
Correlates of Protection
Despite the success of rotavirus vaccines world wide, suboptimal vaccine efficacy in regions with a high burden of disease continues to present a challenge to worldwide implementation. Improvement in the understanding correlates of protective immunity are needed. Currently there is no defined correlate of protection that translates to Rotavirus vaccine efficacy. This project aims to improve our understanding of the correlations between markers of rotavirus protection and vaccine efficacy. The Enteric Virus Group and Roatvirus group with funding from the Bill and Melinda Gates foundation will study markers that may increase our understanding of vaccine protection and efficacy.
Impact of Birth dose of RV3-BB
Understanding why some vaccine recipients do not respond to an oral rotavirus vaccine is crucial to guide future vaccine strategies. This project will study the relationship between the gut microbiome and vaccine take of the human neonatal rotavirus vaccine, RV3BB provided as a birth or neonatal dose. This project also aims to understand the impact of the human neonatal rotavirus vaccine RV3BB on early immune development. Early stimulation of the mucosal immune system by a live oral vaccine may influence the development of a “normal” microbiome and limit the development of environmental enteropathy. It is also possible that an oral rotavirus vaccine may offer similar non-specific immune benefits as has been observed with OPV. This study will take advantage of the infrastructure and sample collection developed and implemented for the Phase II clinical trials of the RV3-BB vaccine conducted in two high disease burden regions.
- Protease-activated Receptor 1 Plays a Proinflammatory Role in Colitis by Promoting Th17-related Immunity. 2017
- Rotavirus vaccination and intussusception - Science, surveillance, and safety: A review of evidence and recommendations for future research priorities in low and middle income countries. 2016
- Recent advances in characterizing the gastrointestinal microbiome in Crohn's disease: a systematic review. 2015
- Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy: a randomised, double-blind, placebo-controlled trial. 2015
- Rapid diagnostic tests for group A streptococcal pharyngitis: a meta-analysis. 2014
- Evidence of false-positive results in a commercially available rotavirus assay in the vaccine era, Australia, 2011 to 2012. 2013
- Novel G10P rotavirus strain, northern territory, Australia. 2013
- Phase I trial of RV3-BB rotavirus vaccine: a human neonatal rotavirus vaccine. 2013
- Intussusception following rotavirus vaccine administration: Post-marketing surveillance in the National Immunization Program in Australia 2011