Adenovirus vectors are the most frequently used agents for gene therapy, including oncolytic therapy and vaccine development. It’s hard to overestimate the value of adenoviruses during the COVID-19 pandemic as to date four out of four approved viral vector-based SARS-CoV-2 vaccines are developed on adenovirus platform. The vast majority of adenoviral vectors are based on the most studied human adenovirus type 5 (HAdV-C5), however, its immunogenicity often hampers the clinical translation of HAdV-C5 vectors. The search of less seroprevalent adenovirus types led to another species C adenovirus, Adenovirus type 6 (HAdV-C6). HAdV-C6 possesses high oncolytic efficacy against multiple cancer types and remarkable ability to induce the immune response towards carrying antigens. Being genetically very close to HAdV-C5, HAdV-C6 differs from HAdV-C5 in structure of the most abundant capsid protein, hexon. This leads to the ability of HAdV-C6 to evade the uptake by Kupffer cells as well as to distinct opsonization by immunoglobulins and other blood proteins, influencing the overall biodistribution of HAdV-C6 after systemic administration. This review describes the structural features of HAdV-C6, its interaction with liver cells and blood factors, summarizes the previous experiences using HAdV-C6, and provides the rationale behind the use of HAdV-C6 for vaccine and anticancer drugs developments.

Human Adenovirus type 6 (HAdV-C6) is a promising candidate for the development of oncolytic vectors as it has low seroprevalence and the intrinsic ability to evade tissue macrophages. However, its further development as a therapeutic agent is hampered by the lack of convenient cloning methods. We have developed a novel technology when a shuttle plasmid carrying the distal genome parts with modified E1A and E3 regions is recombined in vitro with the truncated HAdV-C6 genome. Using this approach, we have constructed a novel Ad6-hT-GM vector controlled by the hTERT promoter and expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) instead of 6.7K and gp19K E3 proteins. We have demonstrated that control by the hTERT promoter may result in delayed viral replication, which nevertheless does not significantly change the cytotoxic ability of recombinant viruses. The insertion of the transgene by displacing the E3-6.7K/gp19K region does not drastically change the expression patterns of E3 genes; however, mild changes in expression from major late promoter were observed. Finally, we have demonstrated that the treatment of human breast cancer xenografts in murine models with Ad6-hT-GM significantly decreased the tumor volume and improved survival time compared to mock-treated mice.

Human respiratory syncytial virus (RSV) is an RNA virus of the family Pneumoviridae and is a common causative agent of acute respiratory infections. Infect

Respiratory syncytial virus (RSV) is among leading global causes of lower respiratory tract infections, yet data from Russia and other states of the Former Soviet Union (FSU) remain fragmented and structurally inconsistent. This systematic review aims to map and synthesize existing evidence on RSV epidemiology and genotypic distribution across the FSU. Published studies from eLIBRARY and PubMed databases queried for RSV prevalence data, together with public health surveillance datasets, were used to summarize RSV prevalence research across eight FSU countries. Random-effects meta-analysis across age strata showed high prevalence in children before 6 (21%) and a progressive decline with age, which is in agreement with global data. Prevalence estimates showed a high degree of variability partially explained by study scope and clinical presentation. We observed COVID-19-related seasonal disruptions of RSV seasonality, followed by gradual post-pandemic stabilization. Genotypic data reflects global trends with two cosmopolitan clades, A.D and B.D, and their descendants, dominating in the region. The review is limited by uneven geographical and temporal coverage, and scarce data on adults. The review provides the first integrated summary of RSV epidemiology across the FSU and underscores the need for expanded regional surveillance and genomic reporting.

Cholangiocarcinoma (CCA), the second most common liver cancer, remains highly resistant to chemotherapy and radiotherapy, leaving patients with unresectable tumors in urgent need of innovative therapeutic approaches. Adenovirus type 6 (Ad6), a species C human adenovirus, offers significant potential for cancer therapy due to its low seroprevalence compared to Adenovirus type 5 (Ad5) and its ability to evade Kupffer cells during systemic delivery. In this study, we developed a novel oncolytic adenovirus vector based on the Ad6 engineered to express human GM-CSF (Ad6-d24-GM) and evaluated its therapeutic efficacy in a novel immunocompetent, replication-permissive Syrian hamster model of CCA. Intratumoral administration of Ad6-d24-GM significantly suppressed tumor growth and prolonged survival without evidence of toxicity, as indicated by stable body weights and normal liver enzyme levels. Both Ad6-d24-GM and wild-type Ad6 induced robust infiltration of CD4+ and CD8+ T cells, as well as CD68+ macrophages within tumors, demonstrating activation of antitumor immunity. Notably, the Ad6-d24-GM group exhibited a statistically significant increase in CD68+ cells compared to wild-type Ad6, highlighting the immunomodulatory effect of GM-CSF transgene. These results demonstrate the oncolytic and immunostimulatory potential of Ad6-based vectors for CCA treatment and validate the Syrian hamster syngeneic CCA-OF model as a valuable platform for studying oncolytic adenovirus therapies.

Human respiratory syncytial virus (RSV) is an RNA virus of the Pneumoviridae family and is a common causative agent of acute respiratory infections. Infection with this virus is often severe and can result in fatalities and chronic complications, particularly in high-risk groups such as children under the age of 5 and elderly individuals over 65 years old. This review presents the latest data on the taxonomy, virion structure, and genome map of RSV, as well as its role in the etiology of acute respiratory diseases. We have analyzed over 100 publications on RSV genotyping in different parts of the world including Russia published between 2015 and 2023. The genetic composition of RSV isolates in Russia is similar to that in other regions of the world, predominantly represented by genotypes ON1 and BA9. The development of effective vaccines is crucial for successful disease control. The review summarizes global advances in the development of interventions against RSV, emphasizing promising treatments currently undergoing clinical trials and the ones that have recently been approved. Similar interventions (vaccines) are yet to be developed in Russia, but the similarities in genetic composition of RSV in Russia and worldwide offer hope for the rapid development of domestic vaccines against this infection.