Detail

Keywords

Binding Sites, Antibody; Flavivirus

Research interests

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 my group, 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.

Techniques, methods & infrastructure

„State of the art“ basic molecular biology and virology techniques, pro- and eukaryotic expression systems, protein chemical analyses, cell culture techniques, immunological assays for the analysis of antigens and antibodies, viral mutagenesis systems, in vitro assays for viral functions

Selected publications

1. Medits, I. et al., 2020. Extensive flavivirus E trimer breathing accompanies stem zippering of the post‐fusion hairpin. EMBO reports, 21(8). Available at: http://dx.doi.org/10.15252/embr.202050069.
2. Malafa, S. et al., 2020. Impact of flavivirus vaccine-induced immunity on primary Zika virus antibody response in humans D. J. Gubler, ed. PLOS Neglected Tropical Diseases, 14(2), p.e0008034. Available at: http://dx.doi.org/10.1371/journal.pntd.0008034.
3. Heinz, F.X. & Stiasny, K., 2019. When it is better to stay together. Nature Immunology, 20(10), pp.1266–1268. Available at: http://dx.doi.org/10.1038/s41590-019-0497-8.
4. Haslwanter, D. et al., 2017. A novel mechanism of antibody-mediated enhancement of flavivirus infection T. C. Pierson, ed. PLOS Pathogens, 13(9), p.e1006643. Available at: http://dx.doi.org/10.1371/journal.ppat.1006643.
5. Heinz, F.X. & 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(1). Available at: http://dx.doi.org/10.1128/MMBR.00055-16.