Monoclonal antibodies directed against tick-borne encephalitis virus with neutralizing activity in vivo.

Monoclonal antibodies (MoAbs) were raised against the tick-borne encephalitis (TBE) virus, strain K23. The reactivities of 14 selected MoAbs were characterized by ELISA, Western blot analysis, haemagglutination inhibition, immunoprecipitation, in vivo protection and in vitro neutralization tests. All MoAbs reacted only with the glycoprotein E. The binding epitope of one MoAb could be delimited by a synthetic peptide to amino acids 306-339 representing one immunodominant loop structure of the glycoprotein E. The MoAbs exhibited individual reactivities against 13 different TBE virus isolates in ELISA and immunoblot test ranging from type-specific reactions to a broad reactivity with all isolates. Four MoAbs also showed a cross-reaction with other flaviviruses like West Nile virus and/or Yellow fever virus in immunoblot analysis. By competition ELISA the MoAbs could be divided into five different reaction patterns. Four MoAbs showed neutralizing activity with titers in the range 1:140 to 1:5,000 in an in vitro assay. These neutralizing activities could be confirmed by an in vivo mouse challenge model. The MoAbs are useful for diagnostic purposes and for differentiation of TBE virus strains and other flaviviruses.