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 Enteric Diseases group 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.
Another major research area of the group includes identifying and characterising strains of rotavirus circulating across Australia in children with gastroenteritis. Understanding barriers to rotavirus vaccine efficacy and biological mechanisms underlying vaccine escape.
MCRI are seeking to license the RV3-BB vaccine to manufacturing partners who are able to produce the RV3-BB vaccine at large scale to meet global demand. To discuss further please contact:
Business Development Manager
P +613 9936 6316
The Enteric Diseases Group is the Australian National Rotavirus Reference Centre and the WHO International Rotavirus Regional Reference Laboratory. This involves conducting the Australian and WHO International Rotavirus Surveillance Programs.
Australian Rotavirus Surveillance Program
The Australian National Rotavirus Reference Centre undertakes surveillance and characterisation of rotavirus strains causing severe diarrhoea in children and adults throughout Australia. This program undertakes molecular epidemiological studies on the rotavirus strains prevalent in Australia, which allows researchers to track seasonal changes in rotavirus strains causing severe disease. The NRRC have published surveillance data as annual reports in CDI since 1999. The introduction and implementation of national rotavirus vaccine programs across Australia and countries worldwide will increase the selective pressures on circulating wildtype strains, and may result in the emergence of new rotavirus strains. If this happens, these strains will likely impact vaccination programs. Understanding how vaccine introduction has impacted the circulating rotavirus population, by altering the prevalence of common genotypes, selection of antigenic variants and emergence of new or novel types causing disease is the focus of the Enteric Diseases Group. The genetic and biological mechanisms underlying vaccine escape will be studied, providing critical information about the circulating rotavirus population that will help maintain a successful, ongoing rotavirus vaccine program.
WHO Collaborating Centre for Child Health
MCRI contribute to the work of WHO in the development of guidelines for rotavirus diagnostics, typing and characterisation. We supply specialist training on rotavirus detection and characterisation and store and distribute standard diagnostic reference rotavirus strains and cell lines to WHO affiliated laboratories. The WHO Collaborating Centre also studies the molecular evolution of rotavirus strains causing disease.
WHO Rotavirus Regional Reference Laboratory for the Western Pacific Region.
The WHO Regional Reference Laboratory situated at MCRI supports Government and Reference Laboratories in the Western-Pacific region in the laboratory diagnosis of rotavirus infection. The Labortaory also provides quality control validation and confirmatory testing of selected stool samples and genotyped rotavirus strains referred by national laboratories and characterize untypable and unusual rotavirus strains. The Laboratory participates in the WHO annual proficiency testing and quality control program and the inter-regional quality control program. Support is provided to national network laboratories in addressing laboratory problems and participates in training of national laboratory staff.
Development of a low cost oral Rotavirus vaccine (RV3-BB)
The Enteric Diseases 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 a Phase II dose ranging immunogenicity study is being conducted in Malawi, Africa.
Phase II dose ranging study of RV3-BB in Malawi
This Phase II study, ongoing 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 worldwide, 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 and genetic factors such as blood group antigens and secretor status on vaccine performance.
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, RV3-BB provided as a birth or neonatal dose. This project also aims to understand the impact of the human neonatal rotavirus vaccine RV3-BB 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 Oral Polio Vaccine. 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.
- Characterization of the fecal virome in dogs with chronic enteropathy. 2018
- Gamma-irradiated rotavirus: A possible whole virus inactivated vaccine. 2018
- Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth. 2018
- Molecular characterisation of rotavirus strains detected during a clinical trial of the human neonatal rotavirus vaccine (RV3-BB) in Indonesia. 2018
- Multivalent Rotavirus Vaccine and Wild-type Rotavirus Strain Shedding in Australian Infants: A Birth Cohort Study. 2018
- Rotavirus Vaccination and the Global Burden of Rotavirus Diarrhea Among Children Younger Than 5 Years. 2018
- Rotavirus vaccine: a single birth dose? 2018
- Serological responses to rotavirus NSP2 following administration of RV3-BB human neonatal rotavirus vaccine. 2018
- Single-dose rotavirus vaccine at birth: is it effective or safe? - Authors' reply. 2018
- Trace Element Provision in Parenteral Nutrition in Children: One Size Does Not Fit All. 2018
- Characterisation of the canine faecal virome in healthy dogs and dogs with acute diarrhoea using shotgun metagenomics. 2017
- Detection of viruses in weekly stool specimens collected during the first 2 years of life: A pilot study of five healthy Australian infants in the rotavirus vaccine era. 2017
- Etiology of Severe Acute Watery Diarrhea in Children in the Global Rotavirus Surveillance Network Using Quantitative Polymerase Chain Reaction. 2017
- Microbial Factors Associated with Postoperative Crohn's Disease Recurrence. 2017
- Nutritional status, exclusive breastfeeding and management of acute respiratory illness and diarrhea in the first 6 months of life in infants from two regions of Indonesia. 2017
- Rotavirus shedding following administration of RV3-BB human neonatal rotavirus vaccine. 2017
- Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand. 2017
- The innate immune receptor MDA5 limits rotavirus infection but promotes cell death and pancreatic inflammation. 2017
- CNS-specific regulatory elements in brain-derived HIV-1 strains affect responses to latency-reversing agents with implications for cure strategies. 2016
- Emergence of a novel equine-like G3P inter-genogroup reassortant rotavirus strain associated with gastroenteritis in Australian children. 2016
- Increased Rotavirus Prevalence in Diarrheal Outbreak Precipitated by Localized Flooding, Solomon Islands, 2014. 2016
- Options for improving effectiveness of rotavirus vaccines in developing countries. 2016
- A high burden of late-onset sepsis among newborns admitted to the largest neonatal unit in central Vietnam. 2015
- Are identity badges and lanyards in pediatrics potentially contaminated with viral pathogens? 2015
- Association between specific mucosa-associated microbiota in Crohn's disease at the time of resection and subsequent disease recurrence: a pilot study. 2015
- Australian Rotavirus Surveillance Program annual report, 2014. 2015
- Comparison of test specificities of commercial antigen-based assays and in-house PCR methods for detection of rotavirus in stool specimens. 2015
- Conquering rotavirus: from discovery to global vaccine implementation. 2015
- Emerging OP354-Like P Rotaviruses Have Rapidly Dispersed from Asia to Other Continents. 2015
- Genome-Wide Evolutionary Analyses of G1P Strains Isolated Before and After Rotavirus Vaccine Introduction. 2015
- HIV-1 transcriptional regulation in the central nervous system and implications for HIV cure research. 2015
- Morbidity and mortality in hospitalised neonates in central Vietnam. 2015
- 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
- Genetic characterization of a novel G3P rotavirus strain causing gastroenteritis in 12 year old Australian child. 2014
- Outcomes of childhood asthma to the age of 50 years. 2014
- Rotavirus infection induces transient pancreatic involution and hyperglycemia in weanling mice. 2014
- SNP genotyping of animal and human derived isolates of Mycobacterium avium subsp. paratuberculosis. 2014
- The association between childhood asthma and adult chronic obstructive pulmonary disease. 2014
- Trends in eczema, rhinitis, and rye grass sensitization in a longitudinal asthma cohort. 2014
- Bacteriophages in gut samples from pediatric Crohn's disease patients: metagenomic analysis using 454 pyrosequencing. 2013
- Changes in the epidemiology of gastroenteritis in a paediatric short stay unit following the introduction of rotavirus immunisation. 2013
- Crohn’s disease: towards improving postsurgical outcomes. 2013
- Enteral nutrition in Crohn's disease: an underused therapy 2013
- Identification and characterization of antibody-binding epitopes on the norovirus GII.3 capsid. 2013
- Impact of ethnicity, geography, and disease on the microbiota in health and inflammatory bowel disease. 2013
- Pseudomonas infection in children with early-onset Crohn's disease: an association with a mutation close to PSMG1. 2013
- The importance of intergenic recombination in norovirus GII.3 evolution. 2013
- TLR4, IL10RA, and NOD2 mutation in paediatric Crohn's disease patients: an association with Mycobacterium avium subspecies paratuberculosis and TLR4 and IL10RA expression. 2013
- Yellow is pale: The complications and challenges of late diagnosis of extrahepatic biliary atresia 2013
- Bacterial Dysbiosis Associated With Crohn’s Disease: Advances in Gut Metagenomic Analysis 2012
- Characterisation of a G9P rotavirus strain identified during a gastroenteritis outbreak in Alice Springs, Australia post Rotarix (TM) vaccine introduction 2012
- Characterization of the gastrointestinal microbiota in health and inflammatory bowel disease. 2012
- Current knowledge and systematic review of viruses associated with Crohn's disease. 2012
- Group A rotavirus universal mass vaccination: how and to what extent will selective pressure influence prevalence of rotavirus genotypes? 2012
- Identification of Strains of RotaTeq Rotavirus Vaccine in Infants With Gastroenteritis Following Routine Vaccination 2012
- Rotavirus cerebellitis: new aspects to an old foe? 2012
- Rotavirus genotypes in Malaysia and Universal rotavirus vaccination 2012
- Selection and evolutionary analysis in the nonstructural protein NSP2 of rotavirus A 2012
- Surveillance and molecular characterization of group a rotaviruses in goroka, Papua New Guinea 2012
- Case-control evaluation of the effectiveness of the G1P human rotavirus vaccine during an outbreak of rotavirus G2P infection in central Australia. 2011
- Characterization of norovirus strains in Australian children from 2006 to 2008: Prevalence of recombinant strains. 2011
- Comparative evolution of GII.3 and GII.4 norovirus over a 31-year period 2011
- Distribution of Rotavirus Genotypes After Introduction of Rotavirus Vaccines, Rotarix (R) and RotaTeq (R), into the National Immunization Program of Australia 2011
- Exploring the Zoonotic Potential of Mycobacterium avium Subspecies paratuberculosis through Comparative Genomics 2011
- Expression profile of genes involved in pathogenesis of paediatric Crohn's disease. 2011
- Identification of an Antibody Binding Epitope on the Rotavirus Non-Structural Protein NSP2 Using Phage Display Analysis. 2011
- Mycobacterium avium Subspecies paratuberculosis in Children with Early-onset Crohn's Disease: A Longitudinal Follow-up Study 2011
- Phylogenetic analysis of rotavirus A NSP2 gene sequences and evidence of intragenic recombination. 2011
- Rare Rotavirus Strains in Children with Severe Diarrhea, Malaysia 2011
- Reduction in Rotavirus-associated Acute Gastroenteritis Following Introduction of Rotavirus Vaccine Into Australia's National Childhood Vaccine Schedule 2011
- Uniformity of rotavirus strain nomenclature proposed by the Rotavirus Classification Working Group (RCWG) 2011
- World Health Organisation
- PT BioFarma
- Centres for Disease Control and prevention
- University of Georgia
- University of Melbourne
- Telethon Institute
- St Vincent’s Hospital
- Monash University
- Baylor College of Medicine
- University of Otago
- Universitas Gadjah Mada
- Royal Melbourne Institute of Technology
- Malawi Liverpool Wellcome Trust
- University of Liverpool