Antibody ratios against NS1 antigens of tick-borne encephalitis and West Nile viruses support differential flavivirus serology in dogs
L. Könenkamp, U. Ziegler, T. Naucke, M.H. Groschup, I. Steffen
Transboundary and Emerging Diseases, June 2022 69(7)
Abstract: Flavivirus diagnostics are complicated by substantial cross-reactivity of antibodiesbetween different flavivirus species. This is of particular importance in regions withmultiple endemic flaviviruses in co-circulation. Tick-borne encephalitis virus (TBEV) isthe causative agent of tick-borne encephalitis, the most common infection of the cen-tral nervous system in endemic regions of Europe and Asia. Since 2018, the relatedWest Nile virus (WNV) has spread to Germany where its geographic distributionoverlaps with TBEV endemic regions. Besides humans, various animal species aresusceptible to TBEV and WNV infection. To compare antibody responses againstthese flaviviruses and test for cross-reactivity, we developed a multi-species luciferaseimmunoprecipitation system antibody detection assay for several different antigens.We performed a serosurvey of 682 dogs from five different European countries todetect antibodies against TBEV and WNV. Twelve specimens were positive for TBEVNS1 only and seven for WNV NS1 only. Two specimens were reactive to both NS1antigens and another two were equivocal for WNV NS1. Interestingly, 89.5% of pos-itive specimens had TBEV/WNV or WNV/TBEV signal ratios of 10 to >300 betweenindividual NS1 antigens, allowing for a clear distinction between the two viruses. Theremaining 10.5% of reactive specimens showed a five- to 10-fold difference betweenthe two viruses and included possible dual exposures to both viruses. In contrast,equivocal samples showed low signal ratios between the NS1 antigens, suggestingunspecific reactivity. Based on these data, we found the NS1 protein to be a suit-able antigen to distinguish between TBEV- and WNV-specific antibodies in dogs withsensitivity and specificity similar to virus neutralization tests.