Next-generation serology of emergent flavivirus infections
PI(s)/Head responsible for the resource:
Anders Bergqvist
Host organisation(s):
Uppsala University Hospital/Akademiska Sjukhuset Clinical Microbiology, Dept. of Medical Sciences, Uppsala University
Resource description:
The Flavivirus family comprises several mosquitos- or tick-borne infectious agents including tick-borne encephalitis (TBE), dengue virus (DENV), West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever (YF) and Zika virus (ZIKV) and are estimated to annually infect 400 million individuals. The serological diagnostics of these viruses are hampered by several problems due to significant cross reactivity of available tools that often makes it difficult to make a correct assessment of the causative agent and the patient´s immune status. The reason for this unsatisfactory situation is likely that most commercial kits utilize suboptimal antigens based on incomplete polypeptides or single antigens produced in procaryotic or non-mammalian expression systems that lacks the natural systems for protein modifications/processing, which results in antigens that are skewed for linear epitopes and immature structures and lacks the important contribution of native antigen that are fully matured and ultimately are characterized by low analytic specificity and poor correlation with more clinically relevant neutralisation tests. In our previous we have by using BK polyomaviruses (BKV) as model developed serologic diagnostic based on virus-like particles produced in a very efficient expression system that show high similarity with native antigen, high correlation with neutralisation test, and allows proper discrimination of the very closely BKV types I and IV. In this project we will design serologic assays for important flaviviruses based on virus like particles expressed in the same system that are expected to discriminate at least equally well against the much less conserved members of this family and hopefully have a better correlation with protective immunity elicited during natural infection. If this turnout successfully for the existing flaviviruses, this platform can hopefully also be used for a new flavivirus that might emerge in the future.
Contact information:
Anders Bergqvist
Uppsala University Hospital/Akademiska Sjukhuset Clinical Microbiology, Dept of Medical Sciences, Uppsala University
Email: Anders.bergqvist@medsci.uu.se or Anders.bergqvist@akademiska.se