A tick-borne encephalitis virus vaccine based on the European prototype strain induces broadly reactive cross-neutralizing antibodies in humans

J Infect Dis. 2011 Jun 1;203(11):1556-64. doi: 10.1093/infdis/jir122.


After vaccination of humans with tick-borne encephalitis virus (TBEV) vaccine, the extent of cross-neutralization between viruses of the European, Far Eastern, and Siberian subtypes of TBEV and Omsk hemorrhagic fever virus (OHFV) was analyzed. Hybrid viruses that encode the TBEV surface proteins for representative viruses within all subtypes, and OHFV, were constructed using the West Nile virus (WNV) backbone as vector. These viruses allow for unbiased head-to-head comparison in neutralization assays because they exhibit the antigenic characteristics of the TBEV strains from which the surface proteins were derived and showed equivalent biologic properties in cell culture. Human serum samples derived from a TBEV vaccine trial were analyzed and revealed comparable neutralizing antibody titers against European, Far Eastern, and Siberian subtype viruses, indicating equally potent cross-protection against these TBEV strains and a somewhat reduced but still protective neutralization capacity against more distantly related viruses, such as OHFV.

Trial registration: ClinicalTrials.gov NCT00161954 NCT00163540.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Sequence
  • Analysis of Variance
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology*
  • Cell Line, Tumor
  • Chlorocebus aethiops
  • Cloning, Molecular
  • Cross Reactions / immunology*
  • Encephalitis Viruses, Tick-Borne / genetics
  • Encephalitis Viruses, Tick-Borne / growth & development
  • Encephalitis Viruses, Tick-Borne / immunology*
  • Encephalitis, Tick-Borne / blood
  • Encephalitis, Tick-Borne / immunology
  • Encephalitis, Tick-Borne / prevention & control
  • Humans
  • Kinetics
  • Middle Aged
  • Molecular Sequence Data
  • Neutralization Tests
  • Phenotype
  • Sequence Alignment
  • Vero Cells
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*
  • Virus Cultivation
  • West Nile virus / genetics
  • Young Adult


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Viral Vaccines

Associated data

  • ClinicalTrials.gov/NCT00161954
  • ClinicalTrials.gov/NCT00163540