Major Role of S-Glycoprotein in Providing Immunogenicity and Protective Immunity in mRNA Lipid Nanoparticle Vaccines Based on SARS-CoV-2 Structural Proteins.

SARS-CoV-2 variants have evolved over time in recent years, demonstrating immune evasion of vaccine-induced neutralizing antibodies directed against the original S protein. Updated S-targeted vaccines provide a high level of protection against circulating variants of SARS-CoV-2, but this protection declines over time due to ongoing virus evolution. To achieve a broader protection, novel vaccine candidates involving additional antigens with low mutation rates are currently needed. Based on our recently studied mRNA lipid nanoparticle (mRNA-LNP) platform, we have generated mRNA-LNP encoding SARS-CoV-2 structural proteins M, N, S from different virus variants and studied their immunogenicity separately or in combination in vivo. As a result, all mRNA-LNP vaccine compositions encoding the S and N proteins induced excellent titers of RBD- and N-specific binding antibodies. The T cell responses were mainly specific CD4+ T cell lymphocytes producing IL-2 and TNF-alpha. mRNA-LNP encoding the M protein did not show a high immunogenicity. High neutralizing activity was detected in the sera of mice vaccinated with mRNA-LNP encoding S protein (alone or in combinations) against closely related strains, but was undetectable or significantly lower against an evolutionarily distant variant. Our data showed that the addition of mRNAs encoding S and M antigens to mRNA-N in the vaccine composition enhanced the immunogenicity of mRNA-N and induced a more robust immune response to the N protein. Based on our results, we suggested that the S protein plays a key role in enhancing the immune response to the N protein when they are both encoded in the mRNA-LNP vaccine.

In Vitro Efficacy of Antivirals and Monoclonal Antibodies against SARS-CoV-2 Omicron Lineages XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1.

The spread of COVID-19 continues, expressed by periodic wave-like increases in morbidity and mortality. The reason for the periodic increases in morbidity is the emergence and spread of novel genetic variants of SARS-CoV-2. A decrease in the efficacy of monoclonal antibodies (mAbs) has been reported, especially against Omicron subvariants. There have been reports of a decrease in the efficacy of specific antiviral drugs as a result of mutations in the genes of non-structural proteins. This indicates the urgent need for practical healthcare to constantly monitor pathogen variability and its effect on the efficacy of preventive and therapeutic drugs. As part of this study, we report the results of the continuous monitoring of COVID-19 in Moscow using genetic and virological methods. As a result of this monitoring, we determined the dominant genetic variants and identified the variants that are most widespread, not only in Moscow, but also in other countries. A collection of viruses from more than 500 SARS-CoV-2 isolates has been obtained and characterized. The genetic lines XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1, representing the greatest concern, were identified among the dominant variants. We studied the in vitro efficacy of mAbs Tixagevimab + Cilgavimab (Evusheld), Sotrovimab, Regdanvimab, Casirivimab + Imdevimab (Ronapreve), and Bebtelovimab, as well as the specific antiviral drugs Remdesivir, Molnupiravir, and Nirmatrelvir, against these genetic lines. At the current stage of the COVID-19 pandemic, the use of mAbs developed against early SARS-CoV-2 variants has little prospect. Specific antiviral drugs retain their activity, but further monitoring is needed to assess the risk of their efficacy being reduced and adjust recommendations for their use.

Dynamics of SARS-CoV-2 Major Genetic Lineages in Moscow in the Context of Vaccine Prophylaxis.

Findings collected over two and a half years of the COVID-19 pandemic demonstrated that the level immunity resulting from vaccination and infection is insufficient to stop the circulation of new genetic variants. The short-term decline in morbidity was followed by a steady increase. The early identification of new genetic lineages that will require vaccine adaptation in the future is an important research target. In this study, we summarised data on the variability of genetic line composition throughout the COVID-19 pandemic in Moscow, Russia, and evaluated the virological and epidemiological features of dominant variants in the context of selected vaccine prophylaxes. The prevalence of the Omicron variant highlighted the low effectiveness of the existing immune layer in preventing infection, which points to the necessity of optimising the antigens used in vaccines in Moscow. Logistic growth curves showing the rate at which the new variant displaces the previously dominant variants may serve as early indicators for selecting candidates for updated vaccines, along with estimates of efficacy, reduced viral neutralising activity against the new strains, and viral load in previously vaccinated patients.

Estimation of anti-orthopoxvirus immunity in Moscow residents and potential risks of spreading Monkeypox virus.

WHO has declared the outbreak of monkeypox as a public health emergency of international concern. In less than three months, monkeypox was detected in more than 30 000 people and spread to more than 80 countries around the world. It is believed that the immunity formed to smallpox vaccine can protect from monkeypox infection with high efficiency. The widespread use of Vaccinia virus has not been carried out since the 1980s, which raises the question of the level of residual immunity among the population and the identification of groups requiring priority vaccination. We conducted a cross-sectional serological study of remaining immunity among Moscow residents. To do this, a collection of blood serum samples of age group over 30 years old was formed, an in-house ELISA test system was developed, and a virus neutralization protocol was set up. Serum samples were examined for the presence of IgG antibodies against Vaccinia virus (n=2908), as well as for the ability to neutralize plaque formation with a Vaccinia virus MNIIVP-10 strain (n=299). The results indicate the presence of neutralizing antibody titer of 1/20 or more in 33.3 to 53.2% of people older than 45 years. Among people 30-45 years old who probably have not been vaccinated, the proportion with virus neutralizing antibodies ranged from 3.2 to 6.7%. Despite the higher level of antibodies in age group older than 66 years, the proportion of positive samples in this group was slightly lower than in people aged 46-65 years. The results indicate the priority of vaccination in groups younger than 45, and possibly older than 66 years to ensure the protection of the population in case of spread of monkeypox among Moscow residents. The herd immunity level needed to stop the circulation of the virus should be at least 50.25 - 65.28%.

Sputnik Light and Sputnik V Vaccination Is Effective at Protecting Medical Personnel from COVID-19 during the Period of Delta Variant Dominance.

Medical personnel are a group of people that often encounter infectious agents, leading to greater risk of contracting infectious diseases. Specific prevention of diseases in this group is a priority. The epidemiological effectiveness of COVID-19 prevention in the group of medical workers due to the emergence of new variants of concern of the SARS-CoV-2 virus has not been studied in sufficient depth. We conducted a study of the effectiveness of vaccine use to protect medical workers at a large medical center for obstetrics and gynecology in Moscow. Sputnik V and Sputnik Light were the main vaccines used for the prevention of COVID-19. The vaccines are based on a variant of the S-protein of the SARS-CoV-2 virus, with adenovirus serotypes 5 and 26 as the vector for delivery. Vaccination of employees occurred during the period in which the Delta variant was spreading. The overall epidemiological effectiveness was 81.7% (73.1-87.6%) during the period in which the Delta variant was dominant. During the period from the beginning of vaccination (26 November 2020) until 8 February 2022, the overall effectiveness was 89.1% (86.9-91.0%). As expected, the highest effectiveness during this period was obtained in the group that received the third and fourth doses-96.5% (75.0-99.5%). The severity of COVID-19 in the vaccinated group was significantly lower than in the unvaccinated group.

Sputnik V Effectiveness against Hospitalization with COVID-19 during Omicron Dominance.

Mass vaccination campaigns against COVID-19 affected more than 90% of the population in most developed countries. The new epidemiologic wave of COVID-19 has been ongoing since the end of 2021. It is caused by a virus variant B.1.1.529, also known as "Omicron" and its descendants. The effectiveness of major vaccines against Omicron is not known. The purpose of this study is to evaluate the efficacy of the Sputnik V vaccine. The main goal is to assess its protection against hospitalization in the period of Omicron dominance. We conducted our study based on a large clinical center in Moscow (Russia) where 1112 patients were included. We used the case-population method to perform the calculations. The data we obtained indicate that the Omicron variant causes at least 90% of infections in the studied cohort. The effectiveness of protection against hospitalization with COVID-19 in our study was 85.9% (95% CI 83.0-88.0%) for those who received more than one dose. It was 87.6% (95% CI 85.4-89.5%) and 97.0% (95% CI 95.9-97.8%) for those who received more than two or three doses. The effectiveness in cases of more severe forms was higher than for less severe ones. Thus, present study indicates the high protective efficacy of vaccination against hospitalization with COVID-19 in case of Omicron lineage.

Contamination of Hospital Surfaces with Bacterial Pathogens under the Current COVID-19 Outbreak.

The SARS-CoV-2 pandemic remains a global health issue for several reasons, such as the low vaccination rates and a lack of developed herd immunity to the evolution of SARS-CoV-2, as well as its potential inclination to elude neutralizing antibodies. It should be noted that the severity of the COVID-19 disease is significantly affected by the presence of co-infections. Comorbid conditions are caused not only by pathogenic and opportunistic microorganisms but also by some representatives of the environmental microbiome. The presence of patients with moderate and severe forms of the disease in hospitals indicates the need for epidemiological monitoring of (1) bacterial pathogens circulating in hospitals, especially the ESKAPE group pathogens, and (2) the microbiome of various surfaces in hospitals. In our study, we used combined methods based on PCR and NGS sequencing, which are widely used for epidemiological monitoring. Through this approach, we identified the DNA of pathogenic bacteria (Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, CoNS, and Achromobacter spp.) on various surfaces. We also estimated the microbiome diversity of surfaces and identified the potential reservoirs of infections using 16S rRNA profiling. Although we did not assess the viability of identified microorganisms, our results indicate the possible risks of insufficient regular disinfection of surfaces, regardless of department, at the Infectious Diseases Hospital. Controlling the transmission of nosocomial diseases is critical to the successful treatment of COVID-19 patients, the rational use of antimicrobial drugs, and timely decontamination measures.