COVID-19 is a highly contagious respiratory disease with a high number of lethal cases in humans, which causes the need to search for new therapeutic agents. Polysaccharides could be one of the prospective types of molecules with a large variety of biological activities, especially antiviral. The aim of this work was to study the specific antiviral activity of the drug “Immeran” on a model of a new coronavirus infection SARS-CoV-2 in hamsters. Based on the second experiment, intraperitoneal treatment with the drug according to a treatment regimen in doses of 500 and 1000 μg/kg (administration after an hour, then once a day every other day, a total of 3 administrations) was effective, reliably suppressing the replication of the virus in the lungs and, at a dose of 1000 μg/kg, prevented weight loss in animals. In all cases, the treatment stimulated the formation of virus-neutralizing antibodies to the SARS-CoV-2 virus, which suggests that the drug possesses adjuvant properties.

Multiple myeloma (MM or plasma cell myeloma) is a heterogenous B-cell malignant tumor that typically exhibits a high recurrence rate, resistance to drugs, and molecular diversity of tumor subclones. Given the limited efficacy of standard therapy options, cellular immunotherapy featuring a chimeric antigen receptor (CAR) has proven tangible potential in treatment for relapsed and refractory forms of MM. The rational choice of a tumor target which shows high selectivity, stable expression, and biological significance is key to the successful implementation of CAR therapy. This review has summarized and analyzed data from the literature on biological properties, the features of expression, and the clinical development stages of CAR cell products for MM treatment which target BCMA, GPRC5D, FcRH5, SLAMF7, CD38, CD138, TACI, APRIL, CD19, TNFR2, CD44v6, CD70, NKG2D ligands, etc. Special focus is on strategic approaches to overcoming antigenic escape, such as multi-specific CAR constructs, logical activation sequences, and controlled safety systems. The analysis underscores the need for integrating the molecular selection of targets with cutting-edge bioengineering solutions as a key trend for raising the efficacy, stability, and safety of cellular therapy in the case of MM.

BACKGROUND: Unprecedented anti-epidemic measures and the widespread use of vaccines against COVID-19 have reduced the rate of hospitalization and mortality from the disease, but have not stopped the SARS-CoV-2 pandemic spread. The development of live vaccines against COVID-19, capable of providing the formation of a long-term humoral and cellular immune response and cross-protection against new SARS-CoV-2 variants of concern, is relevant. Previously at the I.I. Mechnikov Research Institute of Vaccines and Sera SARS-CoV-2 cold-adapted (ca, cold-adapted) variants were obtained. This work is aimed to search for methodological approaches that allow in vitro screening studies to assess the attenuation (att) phenotype of ca SARS-CoV-2 variants. MATERIALS AND METHODS: The SARS-CoV-2 laboratory strain Dubrovka and its variants were cultured in Vero and Calu-3 cells. Quantitation of the virus was carried out by titration in Vero cells and by real-time RT-PCR. The attenuation (att) phenotype of SARS-CoV-2 variants was determined on an animal model of COVID-19 on Syrian hamsters. RESULTS: In experiments on Syrian hamsters, the presence of the att phenotype in the ca variants of the virus was established. Animals infected with virus ca variants had significantly less weight lost, had less viral load in the lungs and brain and less pronounced pathological changes in the lungs compared to infection with the virulent strain. In vitro experiments on Vero and Calu-3 cells revealed probable attenuation markers of the virus ca variants for syrian hamsters: (1) ability to reproduce at low temperature (ca phenotype); (2) inability to reproduce at 39 C (ts phenotype); (3) changes in the species and tissue specificity of the virus. CONCLUSIONS: The developed methodological approaches to the identification of SARS-CoV-2 attenuation markers are a valuable tool for monitoring the stability of the phenotype of candidate vaccine strains.

Influenza and SARS-CoV-2 are often associated with viral pneumonia, resulting from direct exposure of the virus to lung tissue. 3,3′-Diindolylmethane (DIM) is a naturally occurring substance with multi-target activity, including anti-inflammatory and epigenetic modulation. In this study, we evaluated the therapeutic efficacy in vivo of a DIM formulation with fish oil (Cesarox Epi) against influenza A (H1N1) infection in mice and against SARS-CoV-2 infection in Syrian hamsters. In a model of lethal influenza pneumonia induced by A/California/04/2009 (H1N1)pdm09 virus, we showed that 5 days’ treatment with DIM Epi at 10, 20, and 60 mg/kg/day delayed the time to death, prevented body weight loss, and resulted in significant improvements in survival. DIM Epi tested in hamsters infected with SARS-CoV2 Dubrovka (Wuhan-like) strain at doses 50 and 100 mg/kg/day reduced clinical signs, weight loss, temperature elevation, and lung pathology. In both models of infections, treatment with DIM Epi did not significantly decrease viral titer in the animals’ lungs. DIM Epi and Oseltamivir were more effective against influenza infection when given in combination than given singly, while co-administration of DIM Epi with Molnupiravir did not yield an additive benefit against SARS-CoV-2 infection. These findings support DIM Epi as a promising host-directed adjunct therapy for viral pneumonia with potential to enhance outcomes in respiratory infections.

Background/Objectives: Although the COVID-19 pandemic has ended, emerging SARS-CoV-2 variants remain a future threat. This study evaluated the safety and efficacy of an intranasal live attenuated vaccine (LAV) prototype based on a temperature-sensitive (ts) Omicron-like SARS-CoV-2 mutant in a Syrian hamster COVID-19 model. Methods: SARS-CoV-2 Dubrovka (Wuhan-like), Otradnoe (BA.1.1) and FEB2 (BA.5.2) strains and the ts F-F3 mutant derived from FEB2 were characterized by electron microscopy, nanopore sequencing, cytopathic effect titration, and RT-PCR. In vitro studies used Vero CCL-81 cells; in vivo transmissibility and efficacy studies were assessed in female Syrian hamsters. Serum antibody titers were measured by ELISA and neutralization assays. Immunization efficacy was assessed by weight change; viral loads in the lungs, nasal passages, and brain; and histological examination of the lungs at day 4 post-challenge. Safety criteria included evaluation of pathogenicity and transmissibility in hamsters and ts phenotype stability during prolonged in vitro cultivation. Results: The F-F3 strain displayed a stable ts phenotype in vitro, did not infect hamster lungs or brain, and showed no transmission from immunized to naïve co-housed animals. A single intranasal immunization by F-F3 induced seroconversion, reduced pneumonia severity by 76.2% and 79.5% in two independent experiments (p < 0.01), protected the lungs against productive infection while reducing viral load in the nasal passages, and resulted in no detectable viral transmission after homologous BA.5.2 challenge. Following heterologous Wuhan-like challenge, immunization prevented weight loss and significantly reduced viral loads in the lungs, nasal passages, and brain; however, protection against pneumonia was only modest (18.6%; p < 0.05). Conclusions: Preclinical evaluation of the F-F3-based LAV prototype demonstrated a favorable balance between safety and efficacy. These characteristics support its further consideration as a candidate strain for COVID-19 LAV development.

Multiple myeloma (MM, plasma cell myeloma) is a heterogenous B-cell malignant tumor, which typically exhibits high recurrence rate, resistance to drugs and molecular diversity of tumor subclones. Given limited efficacy of standard therapy options, cellular immunotherapy featuring chimeric antigen receptor (CAR) has proven tangible potential in treatment for relapsed and refractory forms of ММ. Rational choice of a tumor target, which shows high selectivity, stable expression and biological significance, is a key to successful implementation of CAR therapy. This review has summarized and analyzed data from literature on biological properties, features of expression, and clinical development stages of CAR cell products for MM treatment, which target BCMA, GPRC5D, FcRH5, SLAMF7, CD38, CD138, TACI, APRIL, CD19, TNFR2, CD44v6, CD70, NKG2D ligands, etc. Special focus is on strategic approaches to overcoming antigenic escape, such as multi-specific CAR constructs, logical activation sequences and controlled safety systems. The analysis underscores the need for integrating molecular selection of targets with cutting-edge bioengineering solutions as a key trend for raising efficacy, stability and safety of cellular therapy in case of ММ.