On Immunological Studies at Sirius University of Science and Technology.

This short report summarizes the results of recent immunological studies performed at new Sirius University of Science and Technology. The report focuses on studying the features of the immune response to vaccination and revaccination against SARS-CoV-2, as well as on a search of potential agents to prevent infection with this virus.

[On Immunological Studies at Sirius University of Science and Technology].

This short report summarizes the results of recent immunological studies performed at the new Sirius University of Science and Technology. The report focuses on studying the features of the immune response to vaccination and revaccination against SARS-CoV-2, as well as on a search of potential agents to prevent infection with this virus.

Antibodies to the N-Terminal Domain of Angiotensin-Converting Enzyme (ACE2) That Block Its Interaction with SARS-CoV-2 S Protein.

SARS-CoV-2 is a new coronavirus that is the cause of COVID-19 pandemic. To enter the cell, the virus interacts via its surface S protein with angiotensin-converting enzyme 2 (ACE2), the main entry receptor on the cell membrane. Most of protective antibodies, including those induced by vaccinations, target the S protein, preventing its interaction with the ACE2 receptor. We have evaluated an alternative strategy for blocking the S-ACE2 interaction using new antipeptide antibodies to the N-terminus of the ACE2 molecule. These antibodies allow detection of human ACE2 in vitro and ex vivo.

[Bispecific Antibodies: Formats and Areas of Application].

Bispecific antibodies capable of simultaneously binding two targets have been studied for many years with a view to their implementation in clinical practice. Unique biological and pharmacological properties, as well as the diversity of their formats, make it possible to consider bispecific antibodies as promising agents for use in various procedures: from visualization of intracellular processes to targeted anticancer therapy. Bispecific antibodies help to determine more precisely the therapeutic target, thereby increasing the efficiency of therapy and reducing the probability of side effects. The present review describes the main formats of bispecific antibodies, methods for their generation, and possibilities for practical application.

Microbiota Induces Expression of Tumor Necrosis Factor in Postnatal Mouse Skin.

Tumor necrosis factor (TNF) is a pleiotropic cytokine that regulates many important processes in the body. TNF production in a physiological state supports the structure of lymphoid organs and determines the development of lymphoid cells in hematopoiesis. However, chronic TNF overexpression leads to the development of various autoimmune disorders. Sites of TNF production in the naïve state remain unclear due to the lack of in vivo models. In the present study, we used TNF-2A-Kat reporter mice to monitor the expression of TNF in different tissues. Comparative analysis of tissue fluorescence in TNF-2A-Kat reporter mice and wild type mice revealed constitutive expression of TNF in the skin of naïve adult mice. In the skin of TNF-2A-Kat reporter mouse embryos, no statistically significant differences in the expression of TNF compared to wild type animals were observed. Furthermore, we established that local depletion of microflora with topical antibiotics leads to a reduction in the fluorescence signal. Thus, we assume that the skin microflora is responsible for the expression of TNF in the skin of mice.

Rehabilitation outcomes following infections causing spinal cord myelopathy.

STUDY DESIGN: Retrospective, open-cohort, consecutive case series. OBJECTIVE: To describe the demographic characteristics, clinical features and outcomes in patients undergoing initial in-patient rehabilitation after an infectious cause of spinal cord myelopathy. SETTING: Spinal Rehabilitation Unit, Melbourne, Victoria, Australia. Admissions between 1 January 1995 and 31 December 2010. METHODS: The following data were recorded: aetiology of spinal cord infection, risk factors, rehabilitation length of stay (LOS), level of injury (paraplegia vs tetraplegia), complications related to spinal cord damage and discharge destination. The American Spinal Injury Association (ASIA) Impairment Scale (AIS) and functional independence measure (FIM) were assessed at admission and at discharge. RESULTS: Fifty-one patients were admitted (men=32, 62.7%) with a median age of 65 years (interquartile range (IQR) 52-72, range 22-89). On admission, 37 (73%) had paraplegic level of injury and most patients (n=46, 90%) had an incomplete grade of spinal damage. Infections were most commonly bacterial (n=47, 92%); the other causes were viral (n=3, 6%) and tuberculosis (n=1, 2%). The median LOS was 106 days (IQR 65-135). The most common complications were pain (n=47, 92%), urinary tract infection (n=27, 53%), spasticity (n=25, 49%) and pressure ulcer during acute hospital admission (n=19, 37%). By the time of discharge from rehabilitation, patients typically showed a significant change in their AIS grade of spinal damage (P<0.001). They also showed significant improvement (P<0.001) in their FIM motor score (at admission: median=27, IQR 20-34; at discharge: median=66, IQR 41-75). CONCLUSION: Most patients returned home with a good level of functioning with respect to mobility, bladder and bowel status, and their disability improved significantly.

Modern anti-cytokine therapy of autoimmune diseases.

The emergence of genetically engineered biological agents opened new prospects in the treatment of autoimmune and inflammatory diseases. Cytokines responsible for regulation of a wide range of processes during development of the normal immune response are among the most successful therapeutic targets. Studies carried out in recent decades and accompanied by rapid development of biotechnology have promoted establishing in detail the role and place of cytokines in autoimmune and inflammatory pathologies. Nevertheless, mechanisms that underlie anti-cytokine therapy are still not fully understood. This review examines the role of such cytokines as TNF, IL-1, and IL-6 in the development of inflammatory processes and the action mechanisms of their inhibitors.

Differences in variability of hypervariable region 1 of hepatitis C virus (HCV) between acute and chronic stages of HCV infection.

Distinguishing between acute and chronic HCV infections is clinically important given that early treatment of infected patients leads to high rates of sustained virological response. Analysis of 2179 clonal sequences derived from hypervariable region 1 (HVR1) of the HCV genome in samples obtained from patients with acute (n = 49) and chronic (n = 102) HCV infection showed that intra-host HVR1 diversity was 1.8 times higher in patients with chronic than acute infection. Significant differences in frequencies of 5 amino acids (positions 5, 7, 12, 16 and 18) and the average genetic distances among intra-host HVR1 variants were found using analysis of molecular variance. Differences were also observed in the polarity, volume and hydrophobicity of 10 amino acids (at positions 1, 4, 5, 12, 14, 15, 16, 21, 22 and 29). Based on these properties, a classification model could be constructed, which permitted HVR1 variants from acute and chronic cases to be discriminated with an accuracy of 88%. Progression from acute to chronic stage of HCV infection is accompanied by characteristic changes in amino acid composition of HVR1. Identifying these changes may permit diagnosis of recent HCV infection.