Rotavirus Surveillance
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.
