The immune response after vaccination in recipients against different subtypes of tick-borne encephalitis virus (Flaviviridae: Orthoflavivirus)

Full Text

Introduction

The tick-borne encephalitis virus (TBEV) belongs to the Orthoflavivirus genus, Flaviviridae family. TBE is widespread across a large area of continental Eurasia, with cases also reported in the United Kingdom and Japan. Approximately 10,000–12,000 cases of tick-borne encephalitis (TBE) are reported worldwide each year. However, this number is likely to be underestimated due to differences in case reporting between countries [1].

There are three main antigenic subtypes of TBEV: European, Far Eastern, and Siberian. In addition to these three main subtypes, the Baikal subtype has also been identified relatively recently [2] and Himalayan strains have been described as a possible candidate for a new TBEV subtype [3]. The level of homology for strains of different subtypes ranges from 93 to 98% for polyprotein [4].

The distibution range of TBEV subtypes generally corresponds to their names. Thus, the Far Eastern subtype circulates mainly in the Far East–in the Primorsky and Khabarovsk regions of the Russian Federation, China, Mongolia, South Korea and Japan–and is also found in certain areas of Western Siberia [5]. The European subtype is mainly present in European Russia, with outbreaks also detected in Western and Eastern Siberia [1, 2]. The Siberian subtype is the most common among all TBEV subtypes and has been detected throughout almost the entire range of TBEV spread, including northern European countries such as Finland [6], Estonia [7], Latvia [8]. At the same time, the Siberian subtype is the most genetically diverse, with four main lineages described within this subtype: Zausaev, Vasilchenko, Baltic and Ob, each of which has its own range. The Zausaev lineage is the most widespread among the Siberian subtype lineages, found in an area stretching from northwestern and central Russia to Transbaikal and Central Asia. The spread of the Vasilchenko lineage strains is shifted eastward–from Western Siberia, Central and Middle Asia to the Far East [4].

The Baltic lineage is isolated in the Baltic States, northwestern and central Russia, and the Urals, and is rarely found in western Siberia. The Ob lineage has only been found in western Siberia [4].

Currently, the most effective method of preventing TBE is vaccination. Both Russian-made and European vaccines against TBE are approved for use in the Russian Federation. All vaccines are based on inactivated virus. The following locally produced vaccines are available: Tick-borne encephalitis vaccine, cultured, purified, concentrated, inactivated, dry (TBE-Moscow), Klesch-E-Vak and EnceVir. The first two are produced at the M.P. Chumakov Federal Research Center for Immunobiological Preparations of the Russian Academy of Sciences (Polio Institute), while another vaccine, EnceVir, produced by Microgen, is created at a branch of the State Research Center for Virology and Biotechnology Vector. All of the above manufacturers produce vaccines for both adults and children. All Russian vaccines are based on strains of the Far Eastern subtype: The Sofyin strain – TBE-Moscow, Klesch-E-Vak; strain 205 – EnceVir. Two other vaccines approved for use in Russia, FSME-IMMUN and Encepur, are manufactured by foreign companies. These drugs are based respectively on strains Neudoerfl and K23 of the European subtype. Today, Russian-made vaccines based on strains of the Far Eastern subtype of the virus are the most widely used in Russia, while there are no vaccines based on the Siberian subtype, despite the fact that this subtype is the most widespread in Russia and is dominant in most endemic regions. Given this fact, it seems promising to modernize existing Russian drugs and include several virus subtypes in their composition to provide more universal protection for the population in regions with high circulation of different TBEV subtypes.

In the context of immune protection against different subtypes of TBEV, the viral envelope glycoprotein E plays a particularly important role. It mediates virus entry into the cell via clathrin-dependent endocytosis and is the main target for neutralizing antibodies (N_Ab) during infection, as well as in response to vaccination against TBE [9]. This glycoprotein is considered highly conserved, and the main approach to dividing TBEV into subtypes is based on the analysis of marker amino acids of this protein. Thus, at position 206 of the E glycoprotein, strains of the Far Eastern subtype have the amino acid serine (Ser), strains of the Siberian subtype have leucine (Leu), and strains of the European subtype have valine (Val) [10]. The division into lineages within the most diverse Siberian subtype of TBEV, as in the case of division into subtypes, is based on the difference in marker amino acids of glycoprotein E: thus, at position 234, the Zausaev lineage is characterized by the amino acid histidine (His); while the Vasilchenko lineage is characterized by glutamine (Glu). In addition, at least 569 variations of the TBEV glycoprotein E are described in the GenBank database¹. Thus, the antigenic structure of this glycoprotein varies significantly depending on the subtype. Protein E consists of three domains (DI, DII, DIII), and at least 12 different epitopes of its binding to monoclonal antibodies have been identified, characterized by varying degrees of neutralizing ability [9, 11].

N_Ab play a key role in the formation of protective immunity against TBE. An N_Ab titer of 1 : 10 or higher in the serum of vaccinated individuals is considered the most indicative criterion for protection against TBE² [12, 13]. First and foremost, the binding of N_Ab to TBEV triggers a cascade of reactions leading to a full-fledged immune response to infection. Furthermore, antibodies to orthoflaviviruses have been shown to prevent infection of target cells by inhibiting the fusion of membranes within endosomes through cross-linking of glycoprotein E molecules [14, 15]. Other mechanisms of action of N_Ab include blocking the binding of viral particles to cell receptors through steric hindrance.

It has been shown that N_Ab against TBEV may be active against other tick-borne orthoflaviviruses, including Langat virus and Omsk hemorrhagic fever virus [16, 17]. Other studies demonstrate that infections caused by orthoflaviviruses do not lead to the formation of persistent cross-neutralizing antibodies, and cross-neutralization persists for only a few months [18]. Studies of vaccines against TBE have shown that a vaccine based on the European Neudoerfl strain induces N_Ab that provide sufficient protection against all three TBEV subtypes (European, Siberian, and Far Eastern virus subtypes) in mice [19]. TBE-Moscow also demonstrated a wide range of protection against different subtypes of TBEV strains in animal experiments [20]. On the other hand, the results of a study conducted by O.V. Morozova et al. on the immunological effect of domestic and foreign vaccines in experiments on mice show that when immunized with the TBE-Moscow vaccine, the titer of immunoglobulin G (IgG) to the Siberian subtype decreased by half compared to the Far Eastern subtype strain, while the use of the Encepur vaccine did not demonstrate sufficient efficacy when infecting mice with the Siberian subtype [21]. O.S. Afonina et al. came to similar conclusions about the differences in the protective properties of vaccines against strains of different subtypes, as well as the predominance of protection against strains that are genetically identical to the vaccine strains [22]. The study by V.V. Pogodina et al. also showed that the level of antibodies to different subtypes in humans can vary [23]. It can be assumed that this is due to differences in the recognition of glycoprotein E in humans and animal models. Thus, it has been demonstrated that mouse N_Ab most effectively recognize the upper surface of the DIII domain of the E protein, while in humans, antibodies against the DI and DII domains dominate the immune response to TBEV [24].

The issue of cross-protection of N_Ab against different subtypes of TBEV remains relevant, as the effectiveness of vaccines developed on the basis of a single subtype may vary for different subtypes of the virus.

At the same time, it is important to take into account data on N_Ab titers when monitoring the epidemiological effectiveness of vaccine prevention in endemic regions, especially in areas where the Siberian subtype is dominant, such as the Sverdlovsk region.

Furthermore, the scientific literature has not yet determined the optimal number of revaccinations required to effectively maintain the level of protection against TBEV in vaccinated individuals [25, 26].

The aim of this study is to investigate the post-vaccination immune response against tick-borne encephalitis virus in recipients immunized with domestic vaccines against four virus strains belonging to different subtypes: Siberian, Far Eastern and European.

Materials and methods

The following reference strains of TBEV were used in the study:

• Sofyin (GenBank ID: JX498940.1), belonging to the Far Eastern subtype;
• Vasilchenko (GenBank ID: L40361.3) – Siberian subtype;
• Absettarov (GenBank ID: KU885457.1) – European subtype.
• Modern isolate Ekb_1887_1 (GenBank ID: OM363218.1), belonging to the Zausaev lineage of the Siberian subtype.

All viral strains were obtained from the collection of the M.P. Chumakov Research Center for Infectious Diseases and Immunology of the Russian Academy of Sciences (Polio Institute). The study material consisted of 100 blood serum samples from recipients vaccinated against TBE (aged 18–70) living in the Sverdlovsk region [26]. Blood was collected in strict accordance with the ethical standards o the World Association’s Helsinki Declaration “Ethical Principles for Medical Research Involving Human Subjects”³. All recipients signed voluntary informed consent forms before blood sampling. The research protocol was approved by the Ethics Committee of the institution Federal Scientific Research Institute of Viral Infections «Virome» Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Ekaterinburg (Protocol No. 4 dated 09.2022). The number of vaccine doses ranged from 1 to 18. In all serum samples tested, specific IgG antibodies to TBEV were detected in the range of titers 1 : 10–1 : 2500. Commercial enzyme-linked immunosorbent assay (ELISA) kits (Vector-Best CJSC) based on the Far Eastern subtype antigen were used to detect IgG antibodies to the virus. The geometric mean titer of neutralizing antibodies (N_Ab GMT) was assessed in a neutralization reaction on SPEV cell culture (transplantable porcine embryonic kidney cell line) according to a previously described protocol [20]. Calculations were performed in logarithmic units using the Reed and Mench method. The titer value was determined based on the serum dilution at which the number of plaque-forming units decreased by more than 50% compared to the control [26]. To refine the result, interpolation between neighboring dilution points was used. To minimize the limitations of this method (subjectivity in assessing the cytopathic effect, nonlinearity of the neutralization dependence), each sample was examined in three parallel settings, after which the average value was calculated. The minimum detection threshold for N_Ab was 1 : 10.

Statistical analysis of the results was performed using GraphPad Prism (version 8). A two-tailed Student’s t-test was used to assess the significance of differences between groups.

Results

The sera of recipients vaccinated against TBEV were tested for virus-specific IgG antibodies using solid-phase ELISA; the IgG antibody titers obtained ranged from 1 : 10 to 1 : 2500. For further analysis, the results were grouped according to antibody levels (Table 1) [26]:

• specific IgG antibody at a titer of 1 : 500 and below (11% of sera tested);
• IgG antibody at a titer of 1 : 500 to 1 : 1000 (18% of sera tested);
• IgG antibody at a titer of 1 : 1000 to 1 : 1500 (31% of sera tested);
• IgG antibody at a titer of 1 : 1500 to 1 : 2000 (36% of sera tested);
• IgG antibody in a titer of 1 : 2000 and above (4% of sera tested);

Among the recipients whose sera were tested, 92% had been vaccinated 3 times or more.

 

Table 1. Quantitative distribution of recipients’ sera based on IgG antibody titers (as per ELISA data), %

Таблица 1. Количественное распределение сывороток реципиентов по титрам IgG (по данным ИФА), %

Number of vaccinations Количество вакцинаций	Number of samples Количество образцов	IgG antibody titer (ELISA) Титр IgG по данным ИФА
		< 1 : 500	1 : 500–1 : 1000	1 : 1000–1 : 1500	1 : 1500–1 : 2000	> 1 : 2000
1	3	1		2
2	4		2	2		1
3	6		2	1	3
4	17	3	2	6	5	1
5	10	1	2	2	5
6	16	3	4	6	3
7	12	2	3	2	4	1
8	11		2	6	3
9	4			2	2
10	4			1	3
11	4		1	1	2
12	3				3
13	2				1	1
14	1	1
15	1				1
18	1				1
In total / Всего	100	11	18	31	36	4

 

Discussion

A question requiring in-depth study is the dependence of the level of protective antibodies against different TBEV subtypes on the number of immunizations (vaccinations and revaccinations) administered. The results obtained demonstrated a sufficient level of virus-specific antibodies in the sera studied for all TBEV subtypes with 3 or more vaccinations/revaccinations (Table 1). It is important to note that analysis of vaccination certificates in the group with the lowest IgG antibody level (< 1 : 500) revealed deviations from the recommended vaccination schedule: only 2 recipients in this group (18.2%) had a vaccination schedule that fully complied with the official one; Another 6 recipients (54.5%) had minor deviations from the recommended vaccination schedule, such as an increase in the recommended interval between revaccinations from 3 to 4–5 years. Three recipients (27%) in this group had serious deviations from the recommended vaccination schedule, including a break in vaccination of more than 5 years or a single vaccination without revaccination. Of particular interest was a sample with an extremely low, borderline IgG antibody titer of 1 : 20. The vaccination schedule for this recipient differed significantly from the recommended schedule in terms of increasing the number of immunizations. Thus, the following violations were allowed in the vaccination schedule for this recipient: failure to observe the 3-year interval between vaccinations and multiple revaccinations within one year. In this case, we can probably talk about immunological tolerance, since frequent and unregulated revaccination can lead to a decrease in the effectiveness of the immune response [27]. Furthermore, too frequent administration of the vaccine may not give the body enough time to form a full immune response.

Study of neutralizing antibody titers against different subtypes of TBEV

To date, there is no clear data on the degree of cross-protection against different subtypes of TBEV in vaccinated individuals, both at low virus-specific IgG antibody titers (≤ 1 : 500) and at higher IgG antibody titers. In this study, a sample of 100 people vaccinated against TBE from the Sverdlovsk region was used to determine the neutralizing activity of sera against TBE strains belonging to different subtypes (the Vasilchenko strain; a modern strain belonging to the Zausaev branch – Ekb_1887_1; strains of the Far Eastern subtype Sofyin and the European subtype Absettarov). The data obtained, presented in the graph (Figure), show that for all groups, except for the IgG > 1 : 2000, the highest geometric mean antibody titer is characteristic of the Sofyin strain (Far Eastern subtype), since strains of this subtype are used in the production of Russian vaccines against TBE, which is consistent with data obtained earlier on a smaller sample [26]. The group with IgG > 1 : 2000 (Figure) showed the highest N_Ab GMT to strains of the Zausaev lineage. This may be due to the fact that two recipients from this group may have recently had an asymptomatic infection caused by a virus belonging to the Zausaev lineage, which led to an average threefold increase in antibody titers to this TBE lineage compared to the N_Ab GMT to the Sofyin strain. Furthermore, this group consisted of the smallest number of recipients, and thus the results obtained had the most significant impact on the average value.

 

Figure. Correlation of geometric mean titer of neutralizing antibodies (N_Аb GMT) to TBEV strains of different subtypes (Sofyin strain (GenBank ID: JX498940.1) – Far Eastern subtype; strain Vasilchenko (GenBank ID: L40361.3) – Siberian subtype; strain Absettarov (GenBank ID: KU885457.1) – European subtype; strain Ekb_1887_1 (GenBank ID: OM363218.1) belonging to the lineage Zausaev – Siberian subtype) and virus-specific IgG antibody titers.

a – IgG 1 : 500 and below (n = 11); b – IgG 1 : 500–1 : 1000 (n = 18); c – IgG 1 : 1000–1 : 1500 (n = 31); d – IgG 1 : 1500–1 : 2000 (n = 36); e – IgG titer 1 : 2000 and above (n = 4). ns – not significant; * – p < 0.1; ** – p < 0.01; *** – p < 0.001; **** – p < 0.0001.

Рисунок. Соотношение среднего геометрического титра нейтрализующих антител (СГТ NАт ) к штаммам ВКЭ разных субтипов (штамм Софьин (GenBank ID: JX498940.1) – дальневосточный субтип; штамм Васильченко (GenBank ID: L40361.3) – сибирский субтип; штамм Абсеттаров (GenBank ID: KU885457.1) – европейский субтип; современный штамм Екб_1887_1 (GenBank ID: OM363218.1), относящийся к ветви Заусаев, – сибирский субтип) и титров вирусоспецифических IgG.

a – IgG ≤ 1 : 500 (n = 11); б – IgG 1 : 500–1 : 1000 (n = 18); в – IgG 1 : 1000–1 : 1500 (n=31); г – IgG 1 : 1500–1 : 2000 (n = 36); e – IgG в титре ≥ 1 : 2000 (n = 4). ns – не значимо; * – p < 0,1; ** – p < 0,01; *** – p < 0,001; **** – p < 0,0001.

 

The group with the lowest virus-specific IgG antibody titers (≤ 1 : 500) (Figure a) is of particular interest, as it was important to assess the minimum protective titer of N_Ab against all studied subtypes of TBEV strains. In recipients of this group, the formation of a minimally sufficient level of immune protection was recorded exclusively in relation to the Sofyin strain at IgG antibody values ≥ 1 : 100. At the same time, N_Ab titers against strains Ekb_1887_1, Vasilchenko, and Absettarov did not reach the protective minimum (< 1 : 10) [26]. In samples where IgG antibody was below 1 : 100, the formation of the minimum detectable level of N_Аb GMT was not observed even for the Far Eastern subtype strain.

In the subgroup with IgG antibody levels ranging from 1 : 500 to 1 : 2000 (Figure b–d), the formation of stable N_Аb GMT was recorded for all studied virus subtypes. At the same time, in all analyzed groups, a decrease in titers of antigen-specific antibodies to tick-borne encephalitis virus strains that did not match the vaccine by 2 times or more was noted (Table 2). Thus, in samples with IgG antibody titers ranging from 1 : 500 to 1 : 1000 (Figure b), a statistically significant decrease in N_Аb GMT was recorded: on average, 3 times for strains of the Siberian subtype and almost 4 times for strains of the European subtype compared to strains of the subtype homologous to the vaccine. In the sample with IgG levels of 1 : 1000–1 : 1500 (Figure c), a decrease in antibody titers was also noted: by 5 and 2.5 times for strains of the Siberian subtype Ekb_1887_1 and Vasilchenko, respectively, and by 8.5 times for the strain belonging to the European subtype. In the group with IgG antibody levels of 1 : 1500–1 : 2000 (Figure d), a decrease in N_Аb GMT was observed by 3.1 and 2.2 times for strains of the Siberian subtype, which is comparable to the results in the group with IgG antibody levels of 1 : 500–1 : 1000; for the European subtype, a more significant decrease in N_Аb GMT was observed – 4.4 times. The data obtained refine and expand the results previously published on a smaller sample of recipients [26]. It should be noted that the identified decrease in the immune response to heterologous strains may indicate limited cross-protection of the vaccine and dependence of its effectiveness on the virus subtype. Such differences are probably due to the peculiarities of the antigenic structure of individual strains.

 

Table 2. A decrease the GMT N_Ab relative to the Sofyin strain (by a certain number of times) in groups of recipients with indicated titers of virus-specific antibodies

Таблица 2. Снижение СГТ NАт относительно штамма Софьин (кратность) в группах реципиентов с указанными титрами вирусоспецифических антител

Group Группа	EKB_1887_1 Екб_1887_1	Reliability Достоверность	Vasilchenko Васильченко	Reliability Достоверность	Absettarov Абсеттаров	Reliability Достоверность
IgG 100–500	3,0	ns	1,2	ns	3,7	ns
IgG 500–1000	3,4	****	2,4	****	3,8	***
IgG 1000–1500	5,0	**	2,5	*	8,5	***
IgG 1500–2000	3,1	****	2,2	***	4,4	****
IgG > 2000	0,5	ns	1,7	ns	3,1	*
Total Общее	3,9	****	2,4	****	4,9	****

Note. ns – not significant; * – p < 0.1; ** – p < 0.01; *** – p < 0.001; **** – p < 0.0001.

Примечание. ns – не значимо; * – p < 0,1; ** – p < 0,01; *** – p < 0,001; **** – p < 0,0001.

 

Thus, we analyzed the groups in which the comparison of antibody titers was statistically significant and obtained the following results: a 3.9-fold and 2.4-fold decrease in N_Аb GMT to the Siberian subtype strains Ekb_1887_1 and Vasilchenko, respectively; a 4.9-fold decrease in N_Аb GMT to the European subtype strain Absettarov.

Thus, most recipients developed sufficient levels of protective antibodies against various subtypes of TBEV after three or more immunizations. No clear correlation between the number of vaccinations and antibody levels was identified in this study; however, deviation from the vaccination schedule may reduce the effectiveness of the immune response, which emphasizes the need for strict adherence to the recommended vaccination schedule. The results obtained are useful for a comprehensive analysis of the effectiveness of vaccine prevention in the Sverdlovsk region, where the Siberian subtype of TBEV dominates [26].

The data obtained are generally consistent with the previously published results of other authors [19, 20] and demonstrate that vaccination remains a highly effective method of combating TBE in endemic areas of the Russian Federation. Currently, according to SanPiN 3.3686-21, an IgG titer of ≥ 1 : 800 is considered the threshold for protection against TBEV, and a course of revaccination is recommended for IgG antibody titers < 1 : 800⁴. However, the results of this study showed that recipients with virus-specific IgG antibody titers < 1 : 500 are at the highest risk of developing the disease. In this case, the titers of virus-neutralizing antibodies to TBEV strains, heterologous to the vaccine strain, did not exceed the minimum detectable protective value of 1 : 10 in the neutralization reaction, and in cases of IgG 1 : 100, the formation of a minimum protective titer of virus-neutralizing antibodies in the neutralization reaction was not observed even for the vaccine strain Sofyin of the Far Eastern subtype. On the other hand, the results of this study also show that immunization with a single-component vaccine leads to the formation of a lower N_Ab titer against the heterogeneous virus subtype compared to the vaccine strain, which also corresponds to the data obtained by other researchers [21–23]. Taking into account the results obtained, as well as previously published data [21–23], it seems relevant to develop a new vaccine based on the Siberian subtype strain, as it is the most widespread in the Russian Federation.

It should also be taken into account that genetic lineages within the Siberian subtype may have different virulence. Thus, it has been shown that strains isolated from ticks in most cases cause an inapparent form of the disease. Therefore, when deciding on the selection of strains for the development of modern vaccines, greater attention should be paid to strains isolated from humans with manifest forms of TBE [28]. In this context, the genetic lineages of the Siberian subtype – Vasilchenko and Zausaev with the eponymous prototype strains of TBEV – are of interest, since they were isolated from patients with TBE: the Vasilchenko strain – from a patient with a febrile form of TBE in the Novosibirsk region [29]; the Zausaev strain from a patient with a chronic form of TBE in the Tomsk region [29], while representatives of other genetic lineages of the Siberian subtype – Bosnian, Baltic, Ob – were isolated from ticks [4, 30, 31].

Conclusion

1. At virus-specific IgG antibody titers to TBEV of 1 : 500 and above, the formation of N_Ab levels sufficient (> 1 : 10) to protect the body against all studied virus subtypes was observed.
2. A statistically significant decrease in N_Ab titers to strains heterologous to the vaccine was observed: to strains of the Siberian subtype Ekb_1887_1 and Vasilchenko, the decrease was 3.9 and 2.4 times, respectively; for the Absettarov strain (European subtype) – 4.9 times compared to the Sofyin strain (Far Eastern subtype).
3. Individuals with low titers of virus-specific antibodies (1 : 500 and below) were more likely to deviate from the recommended vaccination and revaccination schedule, which emphasizes the necessity for strict adherence to maintain the effective level of immune protection against TBEV, especially against strains of the Siberian and European subtypes.
4. Given the widespread distribution and high genetic variability of the Siberain subtype in the Russian Federation, as well as the limited cross-protection capabilities of existing vaccines, the development of a new vaccine based on the Siberian subtype strain is a high priority objective. Another promising prospect could be the creation of a combined vaccine containing antigens from several virus subtypes, which would provide more universal protection for the population in endemic regions with the most frequent circulation of various TBEV subtypes.

¹ Tick-borne encephalitis virus envelope glycoprotein E - Nucleotide - NCBI. Available at: https://ncbi.nlm.nih.gov/nuccore?term=tick-borne+encephalitis+virus+envelope+glycoprotein+E&cmd=DetailsSearch

²  Vaccines against tick-borne encephalitis: WHO position paper; 2011. Available at: https://who.int/publications/i/item/WHO-WER8624

³ Association of Clinical Trials Organizations (ACTO) ‒ WMA Declaration of Helsinki. Available at: http://acto-russia.org/index.php?option=com_content&task=view&id=21 (accessed: 21.05.2025)

⁴ Resolution of the Chief State Sanitary Doctor of the Russian Federation dated January 28, 2021, No. 4 ‒ Official publication of legal acts. Available at: http://publication.pravo.gov.ru/Document/View/0001202102180019 (accessed May 21, 2025)

About the authors

Ekaterina A. Orlova

M.P. Chumakov Federal Scientific Center for Research and Development of Immunobiological Drugs of the Russian Academy of Sciences (Polio Institute)

Email: orlova_ea@chumakovs.su
ORCID iD: 0009-0009-4175-0493

Junior Researcher, Laboratory of Tick-Borne Encephalitis and Other Viral Encephalitis

Russian Federation, 108819, Moscow

Alla L. Ivanova

M.P. Chumakov Federal Scientific Center for Research and Development of Immunobiological Drugs of the Russian Academy of Sciences (Polio Institute)

Email: ivanova_al@chumakovs.su
ORCID iD: 0009-0002-3086-0581

Employment

Russian Federation, 108819, Moscow

Vladimir A. Mishchenko

Federal Scientific Research Institute of Viral Infections «Virome» Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Email: mischenko_va@niivirom.ru
ORCID iD: 0000-0003-4280-283X

Researcher

Russian Federation, 620030, Ekaterinburg

Ivan P. Bykov

Federal Scientific Research Institute of Viral Infections «Virome» Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Email: i.p.bykov@mail.ru
ORCID iD: 0000-0002-5157-646X

Ph.D. in medicine, Senior Researcher

Russian Federation, 620030, Ekaterinburg

Ivan V. Vyalykh

Federal Scientific Research Institute of Viral Infections «Virome» Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Email: vyalykh_iv@niivirom.ru
ORCID iD: 0000-0002-3123-8359

Ph.D. in veterinary medicine, Head of the Laboratory of Vector-borne Viral Infections and Tick-borne Encephalitis, Lead researcher

Russian Federation, 620030, Ekaterinburg

Natalia L. Fadeeva

5th Military Clinical Hospital of the Troops of the National Guard of the Russian Federation

Email: ntellina@mail.ru
ORCID iD: 0009-0008-3944-3219

the head of the Admissions Department

Russian Federation, 620030, Ekaterinburg

Veronica V. Patlusova

5th Military Clinical Hospital of the Troops of the National Guard of the Russian Federation

Email: patlusovavv@mail.ru
ORCID iD: 0009-0008-5493-7655

Ph.D., Head of the Insurance Medicine Group

Russian Federation, 620030, Ekaterinburg

Mikhail F. Vorovitch

M.P. Chumakov Federal Scientific Center for Research and Development of Immunobiological Drugs of the Russian Academy of Sciences (Polio Institute)

Email: vorovich_mf@chumakovs.su
ORCID iD: 0000-0002-7367-6357

Ph.D. in biology, Head of the Encephalitis Vaccine Department, Leading Researcher of the Laboratory of Tick-borne Encephalitis and Other Viral Encephalitis

Russian Federation, 108819, Moscow

Nadezhda M. Kolyasnikova

M.P. Chumakov Federal Scientific Center for Research and Development of Immunobiological Drugs of the Russian Academy of Sciences (Polio Institute)

Author for correspondence.
Email: kolyasnikova_nm@chumakovs.su
ORCID iD: 0000-0002-9934-2582

Doctor of Medicine, Head of the Laboratory of Tick-borne Encephalitis and Other Viral Encephalitis, Leading Researcher

Russian Federation, 108819, Moscow

References

Supplementary files