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. 2024 Aug;96(8):e29843.
doi: 10.1002/jmv.29843.

A reporter virus particle seroneutralization assay for tick-borne encephalitis virus overcomes ELISA limitations

Rahel Ackermann-Gäumann  1   2 , Alexis Dentand  3 , Reto Lienhard  1   2 , Mohsan Saeed  4   5 , Daniel E Speiser  3 , Margaret R MacDonald  6 , Alix T Coste  1   3 , Valeria Cagno  1   3
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A reporter virus particle seroneutralization assay for tick-borne encephalitis virus overcomes ELISA limitations

Rahel Ackermann-Gäumann et al. J Med Virol. 2024 Aug.

Abstract

Tick-borne encephalitis (TBE) virus is the most prevalent tick-transmitted orthoflavivirus in Europe. Due to the nonspecific nature of its symptoms, TBE is primarily diagnosed by ELISA-based detection of specific antibodies in the patient serum. However, cross-reactivity between orthoflaviviruses complicates the diagnosis. Specificity issues may be mitigated by serum neutralization assays (SNT), although the handling of clinically relevant orthoflaviviruses requires biosafety level (BSL) 3 conditions and they have highly divergent viral kinetics and cell tropisms. In the present study, we established a reporter virus particle (RVP)-based SNT in which the infectivity is measured by luminescence and that can be performed under BSL-2 conditions. The RVP-based SNT for TBEV exhibited a highly significant correlation with the traditional virus-based SNT (R2 = 0.8637, p < 0.0001). The RVP-based assay demonstrated a sensitivity of 92.3% (95% CI: 79.7%-97.4%) and specificity of 100% (95% CI: 81.6%-100%). We also tested the cross-reactivity of serum samples in RVP-based assays against other orthoflaviviruses (yellow fever virus, dengue virus type 2, Zika virus, West Nile virus and Japanese encephalitis virus). Interestingly, all serum samples which had tested TBEV-positive by ELISA but negative by RVP-based SNT were reactive for antibodies against other orthoflaviviruses. Thus, the RVP-based seroneutralization assay provides an added value in clinical diagnostics as well as in epidemiological studies.

Keywords: TBEV; cross‐reactivity; orthoflavivirus; reporter virus particle; serology; seroneutralization.

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References

REFERENCES

    1. Ruzek D, Avšič Županc T, Borde J, et al. Tick‐borne encephalitis in Europe and Russia: review of pathogenesis, clinical features, therapy, and vaccines. Antiviral Res. 2019;164:23‐51. doi:10.1016/j.antiviral.2019.01.014
    1. Martello E, Gillingham EL, Phalkey R, et al. Systematic review on the non‐vectorial transmission of Tick‐borne encephalitis virus (TBEv). Ticks and Tick‐borne Diseases. 2022;13(6):102028. doi:10.1016/j.ttbdis.2022.102028
    1. Lindquist L. Tick‐borne encephalitis. In: Tselis A, ed. Handbook of Clinical NEurology. Elsevier; 2014:531‐559.
    1. Lindquist L, Vapalahti O. Tick‐borne encephalitis. The Lancet. 2008;371(9627):1861‐1871. doi:10.1016/S0140-6736(08)60800-4
    1. Füzik T, Formanová P, Růžek D, Yoshii K, Niedrig M, Plevka P. Structure of tick‐borne encephalitis virus and its neutralization by a monoclonal antibody. Nat Commun. 2018;9(1):436. doi:10.1038/s41467-018-02882-0

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