Image_1_Experimental Evaluation of the Protective Efficacy of Tick-Borne Encephalitis (TBE) Vaccines Based on European and Far-Eastern TBEV Strains in Mice and in Vitro.PDF

<p>Tick-borne encephalitis (TBE), caused by the TBE virus (TBEV), is a serious public health threat in northern Eurasia. Three subtypes of TBEV are distinguished. Inactivated vaccines are available for TBE prophylaxis, and their efficacy to prevent the disease has been demonstrated by years of implication. Nevertheless, rare TBE cases among the vaccinated have been registered. The present study aimed to evaluate the protective efficacy of 4 TBEV vaccines against naturally circulating TBEV variants. For the first time, the protection was evaluated against an extended number of phylogenetically distinct TBEV strains isolated in different years in different territories. The protective effect did not strongly depend on the infectious dose of the challenge virus or the scheme of vaccination. All vaccines induced neutralizing antibodies in protective titers against the TBEV strains used, although the vaccines varied in the spectra of induced antibodies and protective efficacy. The protective efficacy of the vaccines depended on the individual properties of the vaccine strain and the challenge virus, rather than on the subtypes. The neutralization efficiency appeared to be dependent not only on the presence of antibodies to particular epitopes and the amino acid composition of the virion surface but also on the intrinsic properties of the challenge virus E protein structure.</p

The phylodynamics of the rabies virus in the Russian Federation

<div><p>Near complete rabies virus N gene sequences (1,110 nt) were determined for 82 isolates obtained from different regions of Russia between 2008 and 2016. These sequences were analyzed together with 108 representative GenBank sequences from 1977–2016 using the Bayesian coalescent approach. The timing of the major evolutionary events was estimated. Most of the isolates represented the steppe rabies virus group C, which was found over a vast geographic region from Central Russia to Mongolia and split into three groups (C0-C2) with discrete geographic prevalence. A single strain of the steppe rabies virus lineage was isolated in the far eastern part of Russia (Primorsky Krai), likely as a result of a recent anthropogenic introduction. For the first time the polar rabies virus group A2, previously reported in Alaska, was described in the northern part of European Russia and at the Franz Josef Land. Phylogenetic analysis suggested that all currently circulating rabies virus groups in the Russian Federation were introduced within the few last centuries, with most of the groups spreading in the 20^th century. The dating of evolutionary events was highly concordant with the historical epidemiological data.</p></div

Bayesian phylogenetic analysis of near-complete N-gene sequences of the rabies virus strains circulating in the Russian Federation.

<p>Scale bar shows time in years. Branches are color-coded according to described groups. Node posterior probabilities above 95% are shown by black squares at the relevant nodes. Posterior probabilities between 80–95% are indicated by numbers. Posterior probabilities below 80% are not indicated. Sequences obtained in the current study are shown in bold.</p

Study design.

<p>The flow chart represents the study design and performance. The monkey species used in each experiment is shown in red. Vaccine: the name of the vaccine administered before challenge or “no” vaccine is indicated. ^a - the number of monkeys used in each experiment is shown in parenthesis. ^b - the blue framed box represents the section number, which describes the results of each particular experiment. The challenging virus is shown in blue. “Analysis made”: the types of analysis and parameters used to evaluate the model are listed. “Results0 are presented in”: the results presented in figures or tables in the current study are listed.</p

The complete blood count in <i>C. aethiops</i> monkeys before and at the different terms after s/c challenge with 7.3 log₁₀ PFU of OHFV strain Nikitina.

<p>ND – not determined; aspartate aminotransferase (AST); alanine aminotransferase (ALT).</p

Viral titers (log₁₀PFU/ml) in CNS and visceral organs of <i>C. aethiops</i> monkeys, immunized twice with TBE inactivated vaccine (FSME-Immun), and in non-immunized monkeys on the 23–26 days after s/c challenge with 6.7 log₁₀ PFU of TBEV, strain Absettarov.

<p>0–<1 PFU in 0.1 ml of 10% suspension.</p

Histological lesions in the brain of monkeys infected with 6.0 log₁₀ PFU of Abs-18 at the late terms after infection (27–28 days).

<p>A and B. Brainstem (<i>truncus cerebri</i>) of <i>M. fascicularis</i> monkey #26: multiple small vasculitis (1), perivascular edema (2), degenerative changes in neurons (3). Magnification: (A) ×100, (B) ×200. C and D. Subcortical region of <i>M. fascicularis</i> monkey #26: small vasculitis (1) and nodules of neuronophagia (2). Magnification: (C) ×100, (D) ×400. Cortex of cerebellum: E. Fall out of small groups of Purkinje cells in <i>M. fascicularis</i> monkey #34 (1). Magnification ×100.; F. Non-infected normal control. Magnification ×200. Staining by Nissle method was used.</p

Histological lesions in the liver and spleen of <i>M. fascicularis</i> monkey (#26) at the late terms after infection with 6.0 log₁₀ PFU of Abs-18.

<p>A. Liver: lymphohistiocytic infiltration of portal liver tracts (1). Magnification ×200. B. Spleen: reduction of lymphoid follicles (1); depletion of white pulp along the trabecular arteries (2). Magnification ×400. Staining with hematoxylin and eosin was used.</p

Virus titers (log₁₀ PFU/ml) and the presence or absence of viral RNA (+/−) in CNS and visceral organs of <i>C. aethiops</i> monkeys immunized and non-immunized with inactivated vaccine against TBE (EIPVE) on the 14–16 days after challenge with 7.3 log₁₀ PFU of OHFV, strain Nikitina.

<p>0–<1 PFU in 0.4 ml 10% suspension.</p><p>“−”– RT-PCR is negative for viral RNA.</p><p>“+”– RT-PCR is positive for viral RNA.</p

Virus titers in visceral organs and CNS (log₁₀ PFU/ml) of <i>M. fascicularis</i> monkeys s/c inoculated with TBEV Abs-18 or Sof-16 strains at the early terms after infection (8–10 d.p.i.).

<p>0–<1 PFU in 0.2 ml of 10% suspension; s.c. – spinal cord, l.n. – lymph nodes.</p