A Tick-borne Encephalitis Virus Vaccine Based on the European Prototype Strain Induces Broadly Reactive Cross-neutralizing Antibodies in Humans

• Published in: The Journal of infectious diseases 2011-06, Vol.203 (11), p.1556-1564
• Main Authors: Orlinger, Klaus K., Hofmeister, Yvonne, Fritz, Richard, Holzer, Georg W., Falkner, Falko G., Unger, Bernd, Loew-Baselli, Alexandra, Poellabauer, Eva-Maria, Ehrlich, Hartmut J., Barrett, P. Noel, Kreil, Thomas R.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Amino Acid Sequence; Analysis of Variance; Animals; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - biosynthesis; Antibodies, Viral - blood; Antibodies, Viral - immunology; Applied microbiology; Biological and medical sciences; Cell growth; Cell Line, Tumor; Cell lines; Cercopithecus 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; Fundamental and applied biological sciences. Psychology; Humans; Hybridity; Infections; Infectious diseases; Kinetics; Medical sciences; Membrane proteins; Microbiology; Middle Aged; Miscellaneous; Molecular Sequence Data; Neutralization Tests; Omsk hemorrhagic fever virus; Phenotype; Sequence Alignment; Tick borne encephalitis; Tick-borne encephalitis virus; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vero Cells; Viral Vaccines - genetics; Viral Vaccines - immunology; Virology; Virus Cultivation; Viruses; West Nile virus; West Nile virus - genetics; Young Adult
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jir122

After vaccination of humans with tick-borne encephalitis virus (TBEV) vaccine, the extent of crossneutralization 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.