New Neutralizing Epitope Exposed on the Domain II of Tick-Borne Encephalitis Virus Envelope Glycoprotein E

Andrey Matveev; Yana Khlusevich; Irina Kozlova; Leonid Matveev; Lyudmila Emelyanova; Artem Tikunov; Ivan Baykov; Nina Tikunova

doi:10.3390/v15061256

New Neutralizing Epitope Exposed on the Domain II of Tick-Borne Encephalitis Virus Envelope Glycoprotein E

Viruses. 2023 May 26;15(6):1256. doi: 10.3390/v15061256.

Authors

Andrey Matveev¹, Yana Khlusevich¹, Irina Kozlova², Leonid Matveev¹, Lyudmila Emelyanova¹, Artem Tikunov¹, Ivan Baykov¹, Nina Tikunova¹

Affiliations

¹ Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia.
² Federal State Public Scientific Institution "Scientific Centre for Family Health and Human Reproduction Problems", Siberian Branch of Russian Academy of Sciences, 664003 Irkutsk, Russia.

Abstract

Orthoflavivirus encephalitidis, formerly tick-borne encephalitis virus (TBEV), belongs to the Orthoflavivirus genus. TBEV is transmitted by tick bites and infection with TBEV can lead to serious disorders of the central nervous system. In this study, a new protective monoclonal mouse antibody (mAb) FVN-32, with high binding activity to glycoprotein E of TBEV, was selected and examined in post exposure prophylaxis in a mouse model of TBEV infection. BALB/c mice were injected mAb FVN-32 at doses of 200 μg, 50 μg, and 12.5 μg per mouse one day after a TBEV challenge. mAb FVN-32 showed 37.5% protective efficacy when administered at doses of 200 μg and 50 μg per mouse. The epitope for protective mAb FVN-32 was localized in TBEV glycoprotein E domain I+II, using a set of truncated fragments of glycoprotein E. Additionally, the target site recognized by mAb FVN-32 was defined using combinatorial libraries of peptides. Three-dimensional modeling revealed that the site is dspatially close to the fusion loop, but does not come into contact with it, and is localized in a region between 247 and 254 amino acid residues on the envelope protein. This region is conserved among TBEV-like orthoflaviviruses.

Keywords: epitope mapping; flavivirus; protective antibody; protein E; tick-borne encephalitis virus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal
Antibodies, Viral
Encephalitis Viruses, Tick-Borne*
Encephalitis, Tick-Borne*
Epitopes
Glycoproteins
Mice
Mice, Inbred BALB C

Substances

Epitopes
Antibodies, Viral
Glycoproteins
Antibodies, Monoclonal

Grants and funding

This research was funded by the Russian Science Foundation, Project No. 22-74-10103. Escherichia coli strain was obtained from the Collection of Extremophile Microorganisms and Type Cultures of ICBFM SB RAS, which is supported by the Ministry of Education and Science, Project No. 121031300043-8.