The structure of inactivated mature tick-borne encephalitis virus at 3.0 Å resolution

ABSTRACT

Tick-borne encephalitis virus (TBEV) causes a severe disease, tick-borne encephalitis (TBE), that has a substantial epidemiological importance for Northern Eurasia. Between 10,000 and 15,000 TBE cases are registered annually despite the availability of effective formaldehyde-inactivated full-virion vaccines due to insufficient vaccination coverage, as well as sporadic cases of vaccine breakthrough. The development of improved vaccines would benefit from the atomic resolution structure of the antigen. Here we report the refined single-particle cryo-electron microscopy (cryo-EM) structure of the inactivated mature TBEV vaccine strain Sofjin–Chumakov (Far-Eastern subtype) at a resolution of 3.0 Å. The increase of the resolution with respect to the previously published structures of TBEV strains Hypr and Kuutsalo-14 (European subtype) was reached due to improvement of the virus sample quality achieved by the optimized preparation methods. All the surface epitopes of TBEV were structurally conserved in the inactivated virions. ELISA studies with monoclonal antibodies supported the hypothesis of TBEV protein shell cross-linking upon inactivation with formaldehyde.

KEYWORDS:

• Cryo-electron microscopy
• inactivated vaccines
• structural virology
• tick-borne encephalitis virus

Acknowledgements

We thank Dr. Victoria I. Uvarova for the preparation of Figure 5. Monoclonal antibody 14D5 was a kind gift from “Vector-Best” (Novosibirsk, Russia). We thank Dr. A. V. Vlaskina for monoclonal antibody purification.

Disclosure statement

FSASI “Chumakov FSC R&D IBP RAS” (Institute of Poliomyelitis) is the manufacturer of the TBE vaccines based on TBEV strain Sofjin-Chumakov. No other conflicts of interests are reported.

Additional information

Funding

The FSASI Chumakov FSC R&D IBP RAS (Institute of Poliomyelitis) contribution was supported by the State Research Funding from the Ministry of Science and Higher Education of the Russian Federation (project no. FNZG-2024-0005). Highresolution cryo-EM studies were funded by Russian Ministry of Science and Education within the framework of the Federal Scientific and Technical Program for the Development of Synchrotron and Neutron Research and Research Infrastructure for 2019-2027 (Agreement no. 075-15-2021-1355 (12 October 2021)). VRS and EBP acknowledge the support and the use of resources of the Resource Center for Probe and Electron Microscopy at the NRC “Kurchatov Institute.”