Poor virus-specific T-cell responses early after tick-borne encephalitis virus infection correlate with disease severity

ABSTRACT

Tick-borne encephalitis virus (TBEV) infection may cause acute central nervous system inflammation varying in clinical manifestations and severity. A possible correlation of TBEV-specific antibody and cell-mediated immune responses, shortly after infection, with clinical manifestations, severity and long-term outcome has been poorly investigated. In a cohort of thirty early tick-borne encephalitis (TBE) patients, we assessed the magnitude, specificity and functional properties of TBEV-specific T-cell and antibody responses. These responses early during disease were assessed in view of clinical manifestations, severity and long-term outcome. TBEV-specific T-cell responses to C, E, NS1, and NS5 proteins were significantly lower in patients with severe acute illness than in patients with mild TBE. Lower T-cell responses to E, NS1, and NS5 proteins also correlated with the development of meningoencephalomyelitis. Virus-specific antibody titres early after infection did not correlate with disease severity, clinical manifestations, or long-term outcome in this study, possibly due to the small number of patients of which matching serum and peripheral blood mononuclear cells were available. The findings suggest that virus-specific T cells afford a certain degree of protection against the development of severe TBEV-induced disease.

KEYWORDS:

• TBEV; Tick-Borne Encephalitis (TBE); TBEV-specific T-cells; disease severity; outcome

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was funded by the Alexander von Humboldt Foundation in the framework of the Alexander von Humboldt Professorship endowed by the German Federal Ministry of Education and Research; and by the European Union’s Horizon 2020 Research and Innovation Program [grant number 848166 [ISOLDA]]; by Slovenian Research and Innovation Agency [grant numbers P3-0083, P3-0296 and J3-3063] and Network of infrastructure Centres of University of Ljubljana [MRIC-UL-IC-BSL3+]; and by the German Federal Ministry of Education and Research [grant number 01KI1719] as part of the Research Network Zoonotic Infectious Diseases. We acknowledge financial support by the Open Access Publication Fund of the University of Veterinary Medicine Hannover, Foundation.