Identification of Linear Human B-cell Epitopes of Tick-borne Encephalitis Virus

Background: Tick-borne encephalitis (TBE) is a central nervous system infection transmitted to humans by ticks. The causative agent, tick-borne encephalitis virus (TBEV), belongs to the genus Flavivirus (family Flaviviridae), which includes globally important arthropod-borne viruses, such as dengue, Yellow fever, Japanese encephalitis and West Nile viruses. Flaviviruses are highly cross-reactive in serological tests that are currently based on viral envelope proteins. The envelope (E) protein is the major antigenic determinant and it is known to induce neutralizing antibody responses.

Methods: We synthesized the full-length TBEV proteome as overlapping synthetic 18-mer peptides to find dominant linear IgG epitopes. To distinguish natural TBEV infections from responses to TBE immunization or other flavivirus infections, the peptides were probed with sera of patients infected with TBEV, West Nile virus (WNV) or dengue virus (DENV), sera from TBE vaccinees and negative control sera by SPOT array technique.

Results: We identified novel linear TBEV IgG epitopes in the E protein and in the nonstructural protein 5 (NS5).

Conclusions: In this study, we screened TBEV structural and nonstructural proteins to find linear epitopes specific for TBEV. We found 11 such epitopes and characterized specifically two of them to be potential for differential diagnostics. This is the first report of identifying dominant linear human B-cell epitopes of the whole TBEV genome. The identified peptide epitopes have potential as antigens for diagnosing TBEV and to serologically distinguish flavivirus infections from each other.