Doctoral study program: Life Sciences

Supervisor: Pavel Plevka

Topic title: Mechanisms of neutralization of TBEV by polyclonal and monoclonal antibodies

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, antibody, 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.

Start date: September 2026

Sign-up link:https://www.ceitec.eu/mechanisms-of-neutralization-of-tbev-by-polyclonal-and-monoclonal-antibodies/t11639