Dataset on safety and protective efficacy studies of COVID-19 vaccine candidates based on structurally modified plant virus in female hamsters.

This data article is related to the previous research, which addressed the development of a COVID-19 recombinant vaccine candidate. Here, we present the additional data in support of the safety and protective efficacy evaluation of two COVID-19 vaccine candidates based on the coronaviruses' S protein fragments and a structurally modified plant virus - spherical particles. The effectiveness of the experimental vaccines was studied against the SARS-CoV-2 virus in an in vivo infection model in female Syrian hamsters. The body weight of vaccinated laboratory animals was monitored. The histological assessment data of the infected with the SARS-CoV-2 virus hamsters' lungs are provided.

Plant Viruses: New Opportunities under the Pandemic.

During the pandemic, an urgent task has become to develop new vaccine platforms that will help fight the infection caused by SARS-CoV-2 and quickly respond to newly emerging pathogens. Plant viruses can make a significant contribution to the solution of this problem. Phytoviruses, having the properties of any viral particles (self-assembly, immunogenicity, nanosize), are safe for humans since plants and mammals have no common infectious agents. As a result of thermal rearrangement of the tobacco mosaic virus, spherical particles of a protein nature have been obtained, which have unique immunostimulation and adsorption properties and can play the role of a universal adjuvant platform to create vaccines. Based on these particles, a scheme for obtaining vaccine preparations is proposed. This technology resembles a toy construction set for children. The basis is spherical particles, on the surface of which there are toy blocks-antigens. The "blocks" can be removed, added, or replaced, and this does not take much time and resources. Based on spherical particles, a polyvalent vaccine candidate against COVID-19 has been created as an adjuvant platform.

Cardiac 123I-mIBG scintigraphy for prediction of catheter ablation outcome in patients with atrial fibrillation.

BACKGROUND: Previous studies show inconsistent results on the role of innervation imaging (with 123I-mIBG) in predicting late atrial fibrillation (AF) recurrence after catheter ablation (CA). These studies included patients with paroxysmal AF and studied prognostic value of post-CA I-123-mIBG parameters. Current study investigated the ability of pre CA 123-I-mIBG imaging to predict late AF recurrence in patients with persistent AF. METHODS: 123I-mIBG cardiac imaging was performed before CA in 82 patients with persistent AF. Patient was followed for 12 months. RESULTS: Multivariable analysis demonstrated that late heart-to-mediastinum ratio (H/Mlate) and washout rate (WR) were independent predictors of AF recurrence. ROC-curve analysis data showed that H/Mlate <1.6 (sensitivity 73.53%, specificity 81.3%, AUC 0.792, P < .001) and WR > 25.11 (sensitivity 70.6%, specificity 70.8.3%, AUC 0.712, P < .001) indicate high probability of AF relapses during 12 months after CA. CONCLUSION: Pre-CA parameters of global cardiac sympathetic activity estimated by 123I-mIBG scintigraphy are associated with late AF relapses in persistent AF patients with normal LVEF and absence of significant CAD.

A Recombinant Rotavirus Antigen Based on the Coat Protein of Alternanthera Mosaic Virus.

Thanks to their strong immunostimulating properties and safety for humans, plant viruses represent an appropriate basis for the design of novel vaccines. The coat protein of Alternanthera mosaic virus can form virus-like particles that are stable under physiological conditions and have adjuvant properties. This work presents a recombinant human rotavirus A antigen based on the epitope of rotavirus structural protein VP6, using Alternanthera mosaic virus coat protein as a carrier. An expression vector containing the gene of Alternanthera mosaic virus (MU strain) coat protein fused to the epitope of rotavirus protein VP6 was designed. Immunoblot analysis showed that the chimeric protein was effectively recognized by commercial polyclonal antibodies to rotavirus and therefore is a suitable candidate for development of a vaccine prototype. Interaction of the chimeric recombinant protein with the native coat protein of Alternanthera mosaic virus and its RNA resulted in the formation of ribonucleoprotein complexes that were recognized by anti-rotavirus antibodies.

[A Recombinant Rotavirus Antigen Based on the Coat Protein of Alternanthera Mosaic Virus].

Thanks to their strong immunostimulating properties and safety for humans, plant viruses represent an appropriate basis for the design of novel vaccines. The coat protein of Alternanthera mosaic virus can form virus-like particles that are stable under physiological conditions and have adjuvant properties. This work presents a recombinant human rotavirus A antigen based on the epitope of rotavirus structural protein VP6, using Alternanthera mosaic virus coat protein as a carrier. An expression vector containing the gene of Alternanthera mosaic virus (MU strain) coat protein fused to the epitope of rotavirus protein VP6 was designed. Immunoblot analysis showed that the chimeric protein was effectively recognized by commercial polyclonal antibodies to rotavirus and therefore is a suitable candidate for development of a vaccine prototype. Interaction of the chimeric recombinant protein with the native coat protein of Alternanthera mosaic virus and its RNA resulted in the formation of ribonucleoprotein complexes that were recognized by anti-rotavirus antibodies.

[Visualisation and Radiofrequency Ablation of Sympathetic Innervation Loci in the Left Atrium in Patients with Paroxysmal Atrial Fibrillation].

INTRODUCTION: A novel cardiac gamma camera utilizes the radiopharmaceutical Iodine-123-Meta-iodobenzylguanidine (123I-MIBG) to visualize cardiac sympathetic innervation. Physiological accumulation of 123I-mIBG provides an anatomical quantitative determination of the structures of the autonomic nervous system (ANS) with discrete uptake areas (DUA) of sympathetic activity located in the left atrium (LA) corresponding to the main ganglionic plexi (GP) clusters that could not previously be visualized. AIM: to visualize the DUA of the heart in patients with paroxysmal atrial fibrillation (AF) and to assess the effect of radiofrequency ablation (RFA) on DUA in LA. MATERIALS AND METHODS: Computed tomography (CT) of the heart and radionuclide imaging with 123I-mIBG were performed in 15 patients with paroxysmal AF. The results of the study were combined with preliminary taken CT images to create a detailed anatomical map of the sympathetic activity of the heart. The processed images were combined with the 3D reconstruction of the LA, obtained with the navigation system (CARTO 3, CARTO RMT). In DUA, high-frequency stimulation (HFS) followed by RF ablation was performed using the current recommended parameters. RESULTS: Forty-eight DUA (median 3 [3; 3]) were identified. Average activity of DUA was 1315 [1171; 1462] cnt / sec / ml. Positive response to HFS in the DUA was obtained in 8 (53.3 %) patients. Prior to ablation, no response was received to HFS in areas of LA outside the DUA. After ablation, there was no response to HFS in the DUA sites. At repeated scans 3 DUA (median 0 [0; 0]; p<0.001 compared with preoperative data) were observed. Activity of DUA significantly decreased to 819 [684; 955] cnt / sec / ml (p<0.001 as compared with preoperative data). Thirteen of 13 of 15 patients (87 %) had no AF / AT / AFL recurrences for 6 month follow up. CONCLUSION: In patients with AF, the areas of sympathetic activity in LA can be visualized by physiological localized uptake of 123I-mIBG. Radiofrequency catheter ablation can target the identified sympathetic innervation structures in AF patients precisely and effectively.

Surface Charge Mapping on Virions and Virus-Like Particles of Helical Plant Viruses.

Currently, the assembly of helical plant viruses is poorly understood. The viral assembly and infection may be affected by the charge distribution on the virion surface. However, only the total virion charge (isoelectric point) has been determined for most plant viruses. Here, we report on the first application of positively charged magnetic nanoparticles for mapping the surface charge distribution of helical plant viruses. The charge was demonstrated to be unevenly distributed on the surface of viruses belonging to different taxonomic groups, with the negative charge being predominantly located at one end of the virions. This charge distribution is mainly controlled by viral RNA.

Data in support of toxicity studies of structurally modified plant virus to safety assessment.

This data article is related to the research article entitled "Assessment of structurally modified plant virus as a novel adjuvant in toxicity studies" (Nikitin et al., 2018), devoted to the safety study of structurally modified plant virus - spherical particles (SPs). SPs are generated by thermally denatured tobacco mosaic virus (TMV) coat protein and act as effective adjuvant for development of new vaccine candidates. This article reports the additional results on the toxicity studies of TMV SPs. The weight coefficients of laboratory animals internal organs complements the data of the subchronic toxicity studies. Also plaque-forming cell assay, delayed-type hypersensitivity test and peritoneal macrophage assay as a part of immunotoxicity studies of TMV SPs are presented.

Spherical particles derived from TMV virions enhance the protective properties of the rabies vaccine.

In this study the ability of spherical particles (SPs) obtained from the tobacco mosaic virus (TMV) virions to enhance the immunogenic potential of the vaccine was evaluated. TMV SPs were shown to increase the protective properties of the widely used effective Russian adjuvant-free rabies vaccine, composed of killed rabies virions. The results of the NIH potency test showed enhancement of protectivity, that is comparable with the effect of the incomplete Freund׳s adjuvant on the same vaccine.

Assessment of structurally modified plant virus as a novel adjuvant in toxicity studies.

Spherical particles (SPs) generated by thermally denatured tobacco mosaic virus (TMV) coat protein can act as an adjuvant, as they are able to enhance the magnitude and longevity of immune responses to different antigens. Here, the toxicity of TMV SPs was assessed prior to it being offered as a universal safe adjuvant for the development of vaccine candidates. The evaluation included nonclinical studies of a local tolerance following the single administration of TMV SPs, and of the local and systemic effects following repeated administrations of TMV SPs. These were conducted in mice, rats and rabbits. General health status, haematology and blood chemistry parameters were monitored on a regular basis. Also, reproductive and development toxicity were studied. No significant signs of toxicity were detected following single or repeated administrations of the adjuvant (TMV SPs). The absence of toxicological effects following the injection of TMV SPs is promising for the further development of recombinant vaccine candidates with TMV SPs as an adjuvant.

[A case of the fracture of the temporal bone pyramid resulting in the fatal outcome]. / Nabliudenie pereloma piramidki visochnoi kosti, privedshego k letal'nomu iskhodu.

The authors report a clinical case of the fracture of the base of the skull with the concomitant damage to the sigmoid sinus, jugular vein, and internal carotid artery in the temporal bone pyramid. The injury was associated with massive bleeding from the external acoustic canal that resulted in the death of the patient.

Translational Cross-Activation of the Encapsidated RNA of Potexviruses.

We had shown the genomic RNA of potexviruses potato virus X and the alternanthera mosaic virus to be inaccessible in vitro to ribosomes while in intact virion form, but the RNAs can be translationally activated following the binding of movement protein 1 (MP1) to virus particles. Here, we present the results of the follow-up study targeting two more potexvirus species - the Narcissus mosaic virus and the Potato aucuba mosaic virus. We found encapsidated potexviral RNA to share common translational features in vitro and the MP1 to be potent over homological virions of its "own" species and over heterological virions of other species, as well exhibiting selective specificity. Reciprocal cross-activation is observed among viral species phylogenetically either close or distant. There is direct evidence that MP1 binding to the end of the virion is necessary, but not sufficient, for translational activation of encapsidated RNA.

The 5'-proximal region of Potato virus X RNA involves the potential cap-dependent "conformational element" for encapsidation.

Filamentous helical Potato virus X (PVX) can be regarded as one of the well-studied viruses. Nevertheless, some aspects of the PVX assembly remained obscure. Previously, we have shown that the presence of a cap structure at the 5' end of PVX RNA is indispensable for assembly of viral ribonucleoprotein (vRNP) particles varying in length. Here, most significantly, removal of the cap structure from previously capped PVX RNA did not affect the efficiency of decapped RNA molecules to be assembled into vRNP. This result provided evidence that the cap structure by itself does not act as a signal for initiation of vRNP assembly. These observations allowed to presume that the capping triggers some spatial changes in the 5'-proximal site of PVX RNA creating a "conformational encapsidation signal for vRNP assembly", which is capable of triggering vRNP assembly in the absence of cap structure. Apparently, during capping the 5'-proximal segment of PVX RNA acquires a unique conformation which is stable to be retained even after cap removal.

Characteristics of Artificial Virus-like Particles Assembled in vitro from Potato Virus X Coat Protein and Foreign Viral RNAs.

Potato virus X (PVX) and some other potexviruses can be reconstitutedin vitrofrom viral coat protein (CP) and RNA. PVX CP is capable of forming viral ribonucleoprotein complexes (vRNP) not only with homologous, but also with foreign RNAs. This paper presents the structure and properties of vRNP assembledin vitroupon incubation of PVX CP and RNAs of various plant and animal viruses belonging to different taxonomic groups. We have shown that the morphology and translational properties of vRNPs containing foreign (heterologous) RNA are identical to those of homological vRNP (PVX RNA - PVX CP). Our data suggest that the assembly of the "mixed" vRNPin vitrocould be started at the 5'-proximal region of the RNA, producing a helical structure of vRNPs with foreign nucleic acids. The formation of heterologous vRNPin vitrowith PVX CP appears not to require a specific 5' end RNA nucleotide sequence, and the PVX CP seems to be able to pack foreign genetic material of various sizes and compositions into artificial virus-like particles.

[Translational regulation of potato virus X RNA-coat protein complexes: the key role of a coat protein N-terminal peptide].

The efficiency of in vitro translation of potato virus X (PVX) RNA within vRNP complexes assembled from genomic RNA and viral CP was examined. The vRNP particles contain the 5'-proximal RNA segments encapsidated by helically arranged CP head-like portions heterogeneous in length and the CP-free RNA tail. Translation of RNA is completely repressed upon incubation with PVX CP and is accompanied by vRNP particles production. By contrast, translation is activated in vRNPs in vitro assembled using two CP forms, differing in the principals of their N-terminal peptides modification. The N-terminal peptide of PVX CP represents the major phosphorylation site(s) for Thr/Ser-specific protein kinases. It was shown that: (i) CP phosphorylation results in a translational activation of vRNP; (ii) removal of N-terminal peptide from CP abolished activation and CP retains the translation repressing ability. It was suggested that substitution of Ser/Thr residues by non-phosphorylated Ala/Gly in N-terminal peptide of the mutant CP will led to a complete inhibition of vRNP translation. However, opposite results were obtained in our experiments: (i) RNA of such mutant virus (PVX-ST) was efficiently translated within the virions; (ii) RNA of a wild-type (wt) PVX also efficiently translated in mixedly assembled vRNP "wt PVX RNA + PVX-ST CP"; (iii) opposite result (repression of translation) was obtained with "mixed" vRNP (PVX-ST RNA + wtPVX CP). Therefore, the N-terminal peptide located at the surface of the particle and of the particles plays a key role in translation activation of the RNA encapsidated in vRNP and native virions.

["Difficult" duodenal stump in emergency surgery of duodenal ulcer]. / "Trudnaia" duodenal'naia kul'tia v urgentnoi khirurgii iazvennoi bolezni dvenadtsatisperstnoi kishki.

Analysis of surgical prophylactic measures of sutures insufficiency of difficult duodenal stump in stomach resection by Bilrot-II in 110 patients with complications of duodenal ulcers required urgent surgery are presented. In study group (43 patients) complex approach to surgical prophylactic measures including diagnosis and correction of chronic disorders of duodenal passability (revealed in 69.8% cases) and individualization of suturing method of duodenal stump was used. In control group (67 patients) traditional external drainage of stump was used as a main prophylactic measure in high risk of complications, method of stump treatment was not individual. Suture insufficiency of duodenal stump was revealed only in control group in 10.4% (7 patients) with 57.1% mortality (4 patients died). General lethality in Group 1 was 4.7% (2 patients), in 2nd--13.4% (9 patients), 6% operated of them died due to insufficiency of duodenal stump. In the structure of death causes, duodenal stump suture incompetence heads the list (44.4%).

[The surgical treatment of severe forms of alkaline reflux gastritis]. / Khirurgicheskoe lechenie tiazhelykh form shchelochnogo refliuks-gastrita.

An examination of 9 patients with primary and postoperative reflux gastritis has found severe forms subject to surgical correction. When choosing the operative method, not only the intensity of reflux of the duodenal content and the character of alterations of gastric mucosa were taken into consideration but also the cause of chronic disorders of the duodenal patency. In all the patients complete disappearance of preoperative symptoms was noted.