Structural Diversity of Tick-Borne Encephalitis Virus Particles in the Inactivated Vaccine Based on Strain Sofjin

• Published in: Emerging microbes & infections Vol. 13; no. 1; p. 2290833
• Main Authors: Moiseenko, Andrey, Zhang, Yichen, Vorovitch, Mikhail F, Ivanova, Alla L, Liu, Zheng, Osolodkin, Dmitry I, Egorov, Alexey M, Ishmukhametov, Aydar A, Sokolova, Olga S
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 31.12.2024; Taylor & Francis Group
• Subjects: asymmetry; cryoelectron microscopy; image analysis; inactivated vaccines; Tick-borne encephalitis virus; variability analysis; Tick-borne encephalitis virus; asymmetry; inactivated vaccines; cryoelectron microscopy; variability analysis; image analysis
• ISSN: 2222-1751; 2222-1751
• DOI: 10.1080/22221751.2023.2290833

The main approach to preventing tick-borne encephalitis (TBE) is vaccination. Formaldehyde-inactivated TBE vaccines have a proven record of safety and efficiency but have never been characterized structurally with atomic resolution. We report a cryoelectron microscopy (cryo-EM) structure of the formaldehyde-inactivated TBE virus (TBEV) of Sofjin-Chumakov strain representing the Far Eastern subtype. A 3.8  Å resolution reconstruction reveals the structural integrity of the envelope E proteins, specifically the E protein ectodomains. The comparative study shows high structural similarity to the previously published structures of the TBEV European subtype strains Hypr and Kuutsalo-14. A fraction of inactivated virions exhibits asymmetric features including the deformations of the membrane profile. We propose that the heterogeneity is caused by inactivation and perform a local variability analysis on the small parts of the envelope protein shell to reveal membrane curvature features possibly induced by the inactivation. The results of this study will have implications for design of novel vaccines against diseases caused by flaviviruses.