Medical countermeasures against norovirus
Short description
Human norovirus (HuNoV) causes winter vomiting disease and is the most common reason of gastrointestinal infection outbreaks across different environments and all age groups around the world. The virus is highly infectious and makes outbreaks difficult and many cases impossible to control. It has a high impact on societal costs and resources. Despite HuNoV being known for more than 50 years there are still neither preventive nor treatment measures against the virus. Therefore a high need to research on HuNoV remains. Inga Rimkuté's research group focuses on crucial steps towards the development of effective countermeasures against HuNoV: to isolate monoclonal antibodies as well as analyse B cells that protect us against the infection and to develop intestinal organoids that allow HuNoV replication.
Noroviruses are a leading cause of gastrointestinal infections worldwide. Almost 700 million people are affected by the infection annually, where children, the elderly and immunocompromised individuals are the most vulnerable. The disease can be acute, chronic or even fatal, leading to an estimated 200 000 deaths each year. Despite its discovery more than 50 years ago and a continuously high prevalence, there is neither prevention nor treatment available against the infection. Progress has been heavily hampered by a lack of a reliable animal model and a rapid propagation culture for the virus in vitro. Although appearing as a simple non-enveloped RNA virus with only a protein capsid, the virus is vastly diverse. The diversity of noroviruses has adapted to the diversity of the host based on at least histo-blood group antigen (HBGA) phenotype (sugar moieties determined by our genome and present on our mucosal surfaces and secreted fluids). Although certain factors, e.g. HBGAs, have been related to certain norovirus susceptibility, the pathogenesis of human norovirus is unknown.
Our goal is to advance medical countermeasures against norovirus, either as vaccine or monoclonal antibodies. We focus on two essential tools that support major opportunities for the advancement of such measures:
- Monoclonal antibodies. We use a pipeline enabling us to characterize human B cell lineages as well as monoclonal antibodies isolated from the characterized B cells specific to noroviruses.
- Intestinal organoids. We work with organoids isolated from humans and monkeys in order to establish a robust cell culture for norovirus propagation.
Flow cytometry, single-cell sequencing, PCR, RTqPCR, organoid cultures are a few of the assays that we are using. We are closely collaborating with Sahlgrenska University Hospital for human sample pools, and we also work with other labs to enable protein and structural work. Through our collaboration with NIH we work on human norovirus studies in monkeys. Together these studies create possibilities to transition our bench work findings to promising medical countermeasures leading to a better global health.
Inga Rimkuté
Principal Investigator
Affiliation:
Department of Microbiology and Immunology,
Institute of Biomedicine
Group members
Andrew Boucher PhD