Variation of the specificity of the human antibody responses after tick-borne encephalitis virus infection and vaccination

Tick-borne encephalitis (TBE) virus is an important human-pathogenic flavivirus endemic in large parts of Europe and Central and Eastern Asia. Neutralizing antibodies specific for the viral envelope protein E are believed to mediate long-lasting protection after natural infection and vaccination. To...

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Bibliographic Details
Published in:Journal of virology 2014-12, Vol.88 (23), p.13845-13857
Main Authors: Jarmer, Johanna, Zlatkovic, Jürgen, Tsouchnikas, Georgios, Vratskikh, Oksana, Strauß, Judith, Aberle, Judith H, Chmelik, Vaclav, Kundi, Michael, Stiasny, Karin, Heinz, Franz X
Format: Article
Language:English
Subjects:
Adult
Aged
Antibodies, Neutralizing - blood
Antibodies, Viral - blood
Cohort Studies
Encephalitis Viruses, Tick-Borne - immunology
Encephalitis, Tick-Borne - immunology
Epitopes - immunology
Female
Humans
Male
Middle Aged
Vaccines and Antiviral Agents
Viral Envelope Proteins - immunology
Viral Vaccines - administration & dosage
Viral Vaccines - immunology
Young Adult
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Summary:Tick-borne encephalitis (TBE) virus is an important human-pathogenic flavivirus endemic in large parts of Europe and Central and Eastern Asia. Neutralizing antibodies specific for the viral envelope protein E are believed to mediate long-lasting protection after natural infection and vaccination. To study the specificity and individual variation of human antibody responses, we developed immunoassays with recombinant antigens representing viral surface protein domains and domain combinations. These allowed us to dissect and quantify antibody populations of different fine specificities in sera of TBE patients and vaccinees. Postinfection and postvaccination sera both displayed strong individual variation of antibody titers as well as the relative proportions of antibodies to different domains of E, indicating that the immunodominance patterns observed were strongly influenced by individual-specific factors. The contributions of these antibody populations to virus neutralization were quantified by serum depletion analyses and revealed a significantly biased pattern. Antibodies to domain III, in contrast to what was found in mouse immunization studies with TBE and other flaviviruses, did not play any role in the human neutralizing antibody response, which was dominated by antibodies to domains I and II. Importantly, most of the neutralizing activity could be depleted from sera by a dimeric soluble form of the E protein, which is the building block of the icosahedral herringbone-like shell of flaviviruses, suggesting that antibodies to more complex quaternary epitopes involving residues from adjacent dimers play only a minor role in the total response to natural infection and vaccination in humans. Tick-borne encephalitis (TBE) virus is a close relative of yellow fever, dengue, Japanese encephalitis, and West Nile viruses and distributed in large parts of Europe and Central and Eastern Asia. Antibodies to the viral envelope protein E prevent viral attachment and entry into cells and thus mediate virus neutralization and protection from disease. However, the fine specificity and individual variation of neutralizing antibody responses are currently not known. We have therefore developed new in vitro assays for dissecting the antibody populations present in blood serum and determining their contribution to virus neutralization. In our analysis of human postinfection and postvaccination sera, we found an extensive variation of the antibody populations present in se
ISSN:0022-538X
1098-5514
DOI:10.1128/JVI.02086-14