Rotavirus gastroenteritis still causes up to 125 000 deaths in children under the age of five annually worldwide, and remains a leading cause of severe acute viral gastroenteritis despite four commercial vaccines being available. The reasons why the commercial vaccines are less effective in children in the developing countries of Africa and Asia are not clear. One reason may be differences between the circulating field strains and the composition of the vaccine strains.
In the molecular virology group, we work towards the development of rational, structure based designed, affordable recombinant vaccines for rotavirus diarrhoea based on regional viral strains and the unravelling of the complexities of the replication cycle of rotavirus that might give insight for developing antiviral strategies or new therapies.
The development of a plasmid-only rotavirus reverse genetics system (RV RG) in 2017 broke a serious technical and research bottleneck. This breakthrough is starting to lead to the better understanding of the virus replication cycle and pathogenesis, which should lead to better strategies to prevent and treat rotavirus infections. Of importance for current rotaviruses research is the need to improve the existing reverse genetics (RG) systems to maintain sufficient efficacy after rational manipulation of genome segments. In many RG systems for other viruses the improvements made to the original system greatly expanded research capabilities and applications of the research.
Virus-like particles (VLP) projects run parallel to our reverse genetics based projects. VLPs are generated in insect cell lines and might eventually be used as dead subunit boosters to improve the partial immunity caused by the current commercial live attenuated vaccines. Rotavirus SA11 live attenuated regional strain vaccine candidates generated in mammalian cell lines by reverse genetics might eventually replace the current commercial live attenuated vaccines. It is quite possible that VLPs could be generated from RV strains that cannot be prepared by reverse genetics due to genetic restrictions.