Share
Mechanisms of Neutralization of TBEV by Polyclonal and Monoclonal Antibodies
Doctoral study program
Life Sciences (Faculty of Science, Masaryk University)
Supervisor
Annotation
Tick-borne encephalitis virus (TBEV) is a medically significant flavivirus causing severe neurological disease in humans. Despite the availability of TBE vaccines, the number of TBE cases continues to rise, necessitating further research into the immune response to TBEV infection to enable the development of therapeutics. The student will use cryo-electron microscopy to determine the structures of antibody-TBEV complexes at near-atomic resolution, revealing binding modes and conformational changes to both the virus envelope proteins and antibodies. Using EMPEM approach the student will analyse polyclonal antibodies from human sera and compare their epitopes to those of functionally well-characterized mabs with different neutralizing and/or enhancing properties.
Recommended literature
- Torrents de la Peña A, Ward AB. Microfluidics combined with electron microscopy for rapid and high-throughput mapping of antibody-viral glycoprotein complexes. Sewall LM, de Paiva Froes Rocha R, Gibson G, Louie M, Xie Z, Bangaru S, Tran AS, Ozorowski G, Mohanty S, Beutler N, Rogers TF, Burton DR, Shaw AC, Batista FD, Chocarro Ruiz B, Nat Biomed Eng. 2025 Jun 3:10.1038/s41551-025-01411-x. doi: 10.1038/s41551-025-01411-x. Epub ahead of print. PMID: 40461656; PMCID: PMC12404239.
- Fuzik T, Formanova P, Ruzek D, Yoshii K, Niedrig M, Plevka P. Structure of tick-borne encephalitis virus and its neutralization by a monoclonal antibody. Nat Commun. 2018;9(1):436. doi: 10.1038/s41467-018-02882-0.
- The structure of immature tick-borne encephalitis virus supports the collapse model of flavivirus maturation. Anastasina M, Füzik T, Domanska A, Pulkkinen LIA, Šmerdová L, Formanová PP, Straková P, Nováček J, Růžek D, Plevka P, Butcher SJ. Sci Adv. 2024 Jul 5;10(27):eadl1888. doi: 10.1126/sciadv.adl1888.
- Kuhn RJ, Zhang W, Rossmann MG, Pletnev SV, Corver J, Lenches E, et al. Structure of dengue virus: implications for flavivirus organization, maturation, and fusion. Cell. 2002;108(5):717-25. doi: 10.1016/s0092-8674(02)00660-8.
Research area
Structural biology, virology
Keywords
cryo-EM, cryo-ET, antybody, polyclonal, monoclonal, Fab, mab
Funding of the PhD candidate
The student will be supported by New technologies for translational research in pharmaceutical sciences /NETPHARM (CZ.02.01.01/00/22_008/0004607).
In the academic year 2026/27 the net income of the CEITEC PhD School student is expected to be at least CZK 29,400 (approx. EUR 1215).
Requirements for candidate
The prospective student should be interested in learning cryo-EM and structure determination approaches. Previous experience with molecular biology, programming, scripting, and data analyses is a plus.
Information about the supervisor
Pavel Plevka is the Research Group Leader and Director of CEITEC Masaryk University in Brno, Czech Republic. Pavel Plevka has determined the structures of several viruses, most notably that of human enterovirus 71 that causes potentially fatal encephalitis in small children. Furthermore, he studied the maturation of the dengue virus. He focuses on cryo-electron microscopy of viruses and other macromolecular complexes. Pavel Plevka studied Molecular Biology and Virology at the Faculty of Science at Charles University in Prague and graduated in 2002, then went on to complete his doctoral studies in Structural Biology in 2009 at Uppsala University in Sweden. For the next four years, he worked as a Postdoctoral Research Associate in Michael Rossmann’s Group at Purdue University in the United States. In 2013, he received an ERC Starting Grant and established his own research group that is focused on Structural Virology at CEITEC Masaryk University in Brno. He is a laureate of the Neuron Prize for Young Scientists and the Werner von Siemens Prize for the most important discovery in basic research. In 2023, he became the Director of CEITEC Masaryk University. In 2022, he was awarded the ERC Consolidator Grant.