Assoc. Prof. Karin Stiasny
Center for Virology
Kinderspitalgasse 15, 1090 Vienna, Austria
Phone: +43 1 40160 65505
E-mail: karin.stiasny@meduniwien.ac.at
Humans infected with flaviviruses produce antibodies which can confer long-lasting immunity to the infecting virus. The protective effect of antibodies is based on their capacity to bind to the surface of virus particles, thereby neutralizing virus infectivity. Immune responses, however, are heterogeneous, and some antibodies are very potent in preventing infection but others are ineffective. There is strong evidence that poorly neutralizing or non-neutralizing antibodies can even enhance flavivirus infection of certain cells. In this research area, we dissect the specificities and functional activities of antibody populations in human blood after different flavivirus infections or vaccinations and determine the balance between neutralizing and infection-enhancing activity. A strong focus is on antibodies that react with all flaviviruses but are unable to inhibit infectivity. These broadly cross-reactive antibodies also hamper the specific laboratory diagnosis of flavivirus infections. Our studies will therefore not only have implications for our basic understanding of immune responses to flaviviruses but also impact the design of diagnostic tests.
These studies are supported by the Austrian Science Fund FWF (P29928-B30) and by intramural funds of the Center for Virology, Medical University of Vienna.
Assoc. Prof. Judith Aberle
Center for Virology
Kinderspitalgasse 15, 1090 Vienna, Austria
Phone: +43 1 40160 65575
E-mail: judith.aberle@meduniwien.ac.at
Virus-specific CD4 T cells are key components of a fully protective immune response against flaviviruses. We study the fine-specificities and functional activities of CD4 T cell responses to vaccination and natural infection with human-pathogenic flaviviruses, i.e. West Nile, Zika, TBE and yellow fever viruses. Our key aims are to enhance our understanding of the molecular mechanisms that guide CD4 T cell epitope selection in infection and vaccination and to understand how protective immune responses are generated. The data will contribute to a molecular understanding of the mechanisms underlying protective immunity and are particularly relevant for designing flavivirus vaccines and the development of diagnostic reagents for analysing T cell responses of vaccine candidates.These studies are supported by the Austrian Science Fund FWF (P29881-B30) and by intramural funds of the Center for Virology, Medical University of Vienna.
Prof. Franz X. Heinz
Center for Virology
Kinderspitalgasse 15, 1090 Vienna, Austria
Phone: +43 1 40160 65500
E-mail: franz.x.heinz@meduniwien.ac.at
Tick-borne encephalitis (TBE) virus is found in many parts of Europe as well as Central and Eastern Asia. There are several lines of evidence that tick-borne flaviviruses differ from mosquito-borne ones in specific aspects of virus structure and replication. In this research area, we investigate the organization and infectious properties of TBE virus particles in immature, mature and intermediate forms. These studies will increase our understanding of the molecular antigenic structure of TBE virus, which is highly relevant for the structure-based design of novel vaccines. A detailed knowledge of the viral life cycle can provide new targets for the development of antiviral agents.
These studies are supported by the Austrian Science Fund FWF (P27501-B21) and by intramural funds of the Center for Virology, Medical University of Vienna.
Selected Publications
Rey FA, Stiasny K, Vaney MC, Dellarole M, Heinz FX. 2018. The bright and the dark side of human antibody responses to flaviviruses: Lessons for vaccine design. EMBO Reports 19:206-224.
Koblischke M, Stiasny K, Aberle SW, Malafa S, Tschouchnikas G, Schwaiger J, Kundi M, Heinz FX, Aberle JH. 2018. Structural influence on the dominance of virus-specific CD4 T cell epitopes in Zika virus infection. Frontiers in Immunology 9: 1196.
Heinz FX, Stiasny K. 2017. The antigenic structure of Zika virus and its relation to other flaviviruses: Implications for infection and immunoprophylaxis. Microbiology and Molecular Biology Reviews 81: e00055-00016.
Haslwanter D, Blaas D, Heinz FX, Stiasny K. 2017. A novel mechanism of antibody-mediated enhancement of flavivirus infection. PLOS Pathogens 13:e1006643.
Koblischke M, Mackroth MS, Schwaiger J, Fae I, Fischer G, Stiasny K, Heinz FX, Aberle JH. 2017. Protein structure shapes immunodominance in the CD4 T cell response to yellow fever vaccination. Scientific Reports 7:8907.
Barba-Spaeth G, Dejnirattisai W, Rouvinski A, Vaney M-C, Medits I, Sharma A, Simon-Lorière E, Sakuntabhai A, Cao-Lormeau V-M, Haouz A, England P, Stiasny K, Mongkolsapaya J, Heinz FX, Screaton GR, Rey FA. 2016. Structural basis of potent Zika–dengue virus antibody cross-neutralization. Nature 536:48-53.
Blazevic J, Rouha H, Bradt V, Heinz FX, Stiasny K. 2016. Membrane anchors of the structural flavivirus proteins and their role in virus assembly. J Virol 90:6365-6378.
Tsouchnikas G, Zlatkovic J, Jarmer J, Strauss J, Vratskikh O, Kundi M, Stiasny K, Heinz FX. 2015. Immunization with immune complexes modulates the fine specificity of antibody responses to a flavivirus antigen. J Virol 89:7970-7978.
Schwaiger J, Aberle JH, Stiasny K, Knapp B, Schreiner W, Fae I, Fischer G, Scheinost O, Chmelik V, Heinz FX.2014. Specificities of human CD4+ T cell responses to an inactivated flavivirus vaccine and infection: correlation with structure and epitope prediction. J Virol. 88(14):7828-42.