Comparison of Two Commercial Tick-Borne Encephalitis Virus IgG Enzyme-Linked Immunosorbent Assays.
Despite the availability of protective vaccines, tick-borne encephalitis virus (TBEV) infections have been increasingly reported to the European Centre for Disease Prevention and Control in the past 2 decades. Since the diagnosis of TBEV exposure relies on serological testing, we compared two commercial enzyme-linked immunosorbent assays (ELISAs), i.e., Immunozym FSME IgG assay (ELISA-1) and Euroimmun FSME Vienna IgG assay (ELISA-2). Both assays use whole TBEV antigens, but they differ in viral strains (Neudoerfl for ELISA-1 and K23 for ELISA-2) and cutoff values. In testing of samples from 398 healthy blood donors, ELISA-1 showed higher reactivity levels than ELISA-2 (P < 0.001), suggesting different assay properties. This finding was supported by Bland-Altman analysis of the optical density at 450 nm (OD450) (mean bias, +0.32 [95% limits of agreement, -0.31 to +0.95]) and persisted after transformation into Vienna units. Concordant results were observed for 276 sera (69%) (44 positive and 232 negative results). Discordant results were observed for 122 sera (31%); 15 were fully discordant, all being ELISA-1 positive and ELISA-2 negative, and 107 were partially discordant (101 being ELISA-1 indeterminate and ELISA-2 negative and 6 having positive or indeterminate reactivity in both ELISAs). Neutralization testing at a 1:10 dilution yielded positive results for 33 of 44 concordant positive sera, 1 of 15 fully discordant sera, and 1 of 33 partially discordant sera. Indirect immunofluorescence testing revealed high antibody titers of ≥100 for yellow fever virus in 18 cases and for dengue virus in one case, suggesting that cross-reactivity contributed to the ELISA-1 results. We conclude that (i) cross-reactivity among flaviviruses remains a limitation of TBEV serological testing, (ii) ELISA-2 revealed reasonable sensitivity and specificity for anti-TBEV IgG population screening of human sera, and (iii) neutralization testing is most specific and should be reserved for selective questions.
Transplantation and Clinical Virology, Department of Biomedicine, University of Basel, Basel, Switzerland.
Fabian H
FH
Weissbach
Transplantation and Clinical Virology, Department of Biomedicine, University of Basel, Basel, Switzerland Division of Infection Diagnostics, Department of Biomedicine, University of Basel, Basel, Switzerland Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland hans.hirsch@unibas.ch.
Hans H
HH
Hirsch
D000914:Antibodies, Viral / Q000097:blood*; D003429:Cross Reactions; D004669:Encephalitis Viruses, Tick-Borne / Q000276:immunology*; D004675:Encephalitis, Tick-Borne / Q000175:diagnosis*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D009500:Neutralization Tests / Q000379:methods; D012680:Sensitivity and Specificity
D000914:Antibodies, Viral; D007074:Immunoglobulin G