Cell-Penetrating Peptides: Emerging Tools for mRNA Delivery

Messenger RNAs (mRNAs) were previously shown to have great potential for preventive vaccination against infectious diseases and therapeutic applications in the treatment of cancers and genetic diseases. Delivery systems for mRNAs, including lipid- and polymer-based carriers, are being developed for improving mRNA bioavailability. Among these systems, cell-penetrating peptides (CPPs) of 4–40 amino acids have emerged as powerful tools for mRNA delivery, which were originally developed to deliver membrane-impermeable drugs, peptides, proteins, and nucleic acids to cells and tissues. Various functionalities can be integrated into CPPs by tuning the composition and sequence of natural and non-natural amino acids for mRNA delivery. With the employment of CPPs, improved endosomal escape efficiencies, selective targeting of dendritic cells (DCs), modulation of endosomal pathways for efficient antigen presentation by DCs, and effective mRNA delivery to the lungs by dry powder inhalation have been reported; additionally, they have been found to prolong protein expression by intracellular stabilization of mRNA. This review highlights the distinctive features of CPP-based mRNA delivery systems.

Predictors of severe forms of rotaviral infection in children

Rotavirus infection (RVI) is one of the most common childhood diseases. The study of predictors of severe forms of this disease is of undoubted interest.Aim. Based on the study of the characteristics of the premorbid background, life history and clinical and laboratory parameters, determine predictors of severe forms of RVI.Patients and methods. In the departments of intestinal infections and resuscitation and intensive care of Pediatric Research and Clinical Center for Infectious Diseases in the period 2018 – 202. a retrospective study of 962 children aged 2 months to 2 years with rotavirus infection was carried out. he severity of the condition was assessed using the Clarke scale. To identify the most significant predictors of the development of severe forms of RVI, two groups of patients were compared: severe (> 16 points) and moderate (≤16 points) forms of RVI. Comparison of the frequency of occurrence of signs in the groups was performed using the Pearson χ2 test and Fisher’s exact method. The forecasting model was developed using discriminant analysis of the statistical package Statistica for Windows.Results. Severe forms of RVI were detected in 65 children. Among the patients with severe forms of RVI, there were no patients with completed preventive vaccination. Patients with severe forms of RVI were admitted to the hospital in the late stages of the disease and had a higher score on the CDS scale. Based on the research carried out, a model for predicting severe forms of RVI was developed. The features included in the model were: the day of illness at admission, the patient’s age, prehospital prescription of antibacterial drugs, the absence of completed vaccination against RVI, and the severity of dehydration. Assessment of the quality of the created model showed that the classification ability was 97.7%.Conclusion. Predictors of severe forms of RVI include admission to a hospital in the late stages of the disease with severe dehydration, early age, prehospital antibiotics and forced transfer to artificial feeding, and absence of completed prophylactic vaccination.

Enhancement of Preventive Vaccination Approaches for Children with Health Problems: Prospective Cohort Study Results

Background. Modern preventive vaccination is intended to protect and enhance the health of every person considering age and health issues. Vaccination of children with chronic diseases in our country remains extremely topical and arguable problem that associated with many pending issues for doctors of various specialties, including those working as primary care specialists.Objective. The aim of the study is to develop major approaches and to prove scientifically the efficacy and safety of preventive vaccination for children with various chronic diseases.Methods. We have conducted comprehensive study of 100 children aged from 1 month to 17 years 11 months. Children were divided into 4 groups according to the specific disease. Vaccinal and infectious history was analyzed. The post-vaccination period was estimated due to the results of the questionnaire completed by parents. Vaccination immunogenicity was estimated based on the results of the level of specific antibodies to various controlled infections (measles, rubella, parotitis, hepatitis B, pertussis, haemophilus influenza type b).Results. Protective titers of antibodies against haemophilus influenza type b were revealed in 96.2% of all examined patients, tetanus and hepatitis B — in 95.2%, against pertussis — in 92.5%, rubella — in 91%, measles — in 87.5%, parotitis — in 71.9%, chickenpox — in 69% children a month after the completed vaccination. The postvaccinal period was characterized as favorable in most patients. Major changes in overall health status occurred after vaccination in 42% of children was the following: subfebrile fever, capriciousness, or fatigue. Local reactions have developed only in 15% of cases.Conclusion. The results of this study have demonstrated the preventive vaccination efficacy and safety in children with various chronic diseases

Using Selected Data-Mining Methods in the Analysis of Data Concerning the Attitudes of Students towards the Issue of Vaccination

Preventive vaccination is one of the greatest successes of modern medicine. The SARS-CoV-2 epidemic, during which vaccination is the main method of prevention against death and severe disease, gave rise to a resurgence of anti-vaccine (anti-vax) movements. The aim of this study was to analyse the attitudes of students towards vaccination and the COVID-19 pandemic. The statistical analysis was performed with the use of the following data-mining methods: correspondence analysis and basket analysis. The obtained results show that students of medicine are characterized with the highest level of knowledge. Students of other medical faculties, on the other hand, have a significantly less uniform views, as do students of non-medical faculties.

Descriptive study of cattle and dog rabies cases in the Sheki-Zagatala region of Azerbaijan (2015–2016): Knowledge, attitudes, and practices of people towards rabies

Every year, rabies causes great damage to human health and the economy of countries around the world. This neurotropic and zoonotic viral disease is endemic to Azerbaijan. This study describes cattle and dog rabies cases identified between 2015 and 2016. In addition, a questionnaire was administered to 100 respondents comprised of case owners, and non-case animal owners, to assess knowledge, attitudes, and practices within this population. The study demonstrates a general lack of knowledge of rabies in the participating communities. The majority of respondents were familiar with rabies and understood that animal bites are a source of transmission. However, many respondents did not know that rabies is preventable and admitted not knowing additional routes of transmission. In addition, there was less perceived risk with contact with animal saliva. Despite free vaccinations in Azerbaijan, only 27 out of 45 dogs in this study were vaccinated. Although educational programming and preventive vaccination of dogs has been implemented, and significant progress has been made in the sphere of epidemiological surveillance and prevention, rabies cases remain problematic in the Sheki-Zagatala region. Regular educational programs for communities, strengthening of the existing vaccination programs, and a comprehensive epidemiological case-control study to identify the disease risk factors could help reduce the burden of rabies in Azerbaijan.

Vaccination Coverage of Children with Epidermolysis Bullosa Against Vaccine Preventable Diseases According to National Preventive Vaccination Programmes: Cross-Sectional Study

Background. Patients with epidermolysis bullosa (EB) have higher risk of developing infectious diseases. Its prevention requires timely vaccination. For now, there are no studies showing vaccination coverage for this category of children. Objective. Our aim was to study vaccination coverage of children with EB according to national preventive vaccination programmes. Methods. This retrospective cross-sectional study examined medical records of patients with EB from Russian Federation and neighbouring countries. Vaccination coverage (completeness and timeliness) and age of immunization initiation were analyzed. Moreover, we have studied the spectrum of early post-vaccine reactions and the course of the post-vaccine period in children with EB vaccinated for the first time. Results. The study included medical records of 134 patients with EB aged from 8 months to 17 years 8 months. Vaccination was performed according to national immunization programs in 37 (28%) children, only 21 cases were carried out in a timely manner. Medical exemptions were the major reason for the refusal of vaccination in most cases (82%). 48 patients with EB were vaccinated against 12 vaccine preventable diseases in the hospital. The post-vaccine period was asymptomatic in 36 (76%) patients, 10 (20%) patients had tenderness and hyperemia at the injection site, 2 (4%) patients had subfebrile fever. Conclusion. Most children with EB are still unvaccinated or vaccinated untimely. Immunization of such children against vaccine preventable disease according to the individual plan can be pretty useful.

Assessment of the COVID-19 epidemiological situation in St. Petersburg

Aim. Identification of epidemiological patterns of the SARS-CoV-2 spread among the population of St. Petersburg during the one-year COVID-19 pandemic period.Materials and methods. The performed analysis focused on the dynamics of COVID-19 cases in St. Petersburg from 2/3/2020 to 4/4/2021 and on the gender-age profile of patients. The information about patients (age, gender, type of the disease, hospitalization, social, and occupational status) was obtained from the database containing the materials from statistical data form No. 058/u.Results. After one year, the dynamics of reported cases of COVID-19 in St. Petersburg shows two cycles of seasonal surge (spring and autumn-winter) and 8 epidemic periods. It has been found that there are no gender-age differences among COVID-19 patients, which can be seen from the relatively similar number of cases among men and women per 100,000 people in each age group during specific epidemic periods. The strong association between clinical manifestations of COVID-19 and the patients' age was detected: Severe cases were more frequently diagnosed in patients over 70 years, regardless of their gender identity. Based on the social and occupational status, the people who were most exposed to the COVID-19 epidemic process were retirees and people whose occupation was associated with health and safety of St. Petersburg. Among the COVID-19 patients, retirees accounted for 13.69% (men) and 17.67% (women). The proportion of healthcare workers was 3.67% (men) and 9.41% (women).Conclusion. It has been assumed that COVID-19 tends to be a seasonal disease featuring annual autumn-winter epidemic cycles. The study addressed prospects of preventive vaccination against COVID-19 in Russia and the importance of tracking the complications pathogenetically associated with the acute phase of the disease in the system of epidemiological surveillance.

EFFICIENCY OF THE FORMATION OF ANTITUMOR IMMUNE RESPONSES IN THE SYSTEM OF PREVENTIVE VACCINATION OF MICE WITH TESTICULAR ANTIGENS

Аppearance of a malignant tumor is associated with impaired mechanisms of proliferation, differentiation, apoptosis ability. However, these changes are not enough for immune system to recognize and destroy mutated cells. Weak immunogenicity of tumor-associated antigens (TAA) and the insufficiency of co-stimulating molecules on the surface of tumor cells is a reason for this phenomenon Since biochemical processes of tumor cells and healthy tissue cells are identical, therefore creation of effective chemotherapeutic drugs is limited not by selectivity of their action. So antitumor vaccination is the most effective specific method for both preventing recurrence of a disease and a therapeutic treatment tool in oncology. Xenogeneic proteins are highly immunogenic and effective in breaking immune tolerance to human analogs. In our work, we used sheep testicular AG as a source xenogenic TAAs. Sheep testicles contain a large set of TAAs. Experimental mice were immunized with type liposomal testicular vaccine from sheep, one month after vaccination, to induce tumor growth, cells of carcinoma LLC were implanted in mouse. The life expectancy of the experimental group of mice was 2 times higher compared to the syngenetic control and 20% of them did not develop the tumor at all. In the spleen of mice who did not have tumors after pre-vaccination sheep liposomal testicular AG, T-regulatory cells and T-memory cells were measured. We found a credible decrease in both naive Treg (CD4+CD25+), activated (CD4+CD25+FoxP3+) and both T-memory (CD4+CD44+) and central memory (CD4+CD44+CD62L+) in spleen pre-vaccination mice with compared to the contral intact spleen. Content of IFNg and IL-10 in supernatants of mouse slenocytes derived from vaccinated mice with no tumors was investigated and showed a reliable decrease in the amount of IL-10, but not IFNg. We believe that immunization with xenogenic tumor AGs can lead to the formation of a protective antitumor response.

Vaccines for Non-Viral Cancer Prevention

Cancer vaccines are a type of immune therapy that seeks to modulate the host’s immune system to induce durable and protective immune responses against cancer-related antigens. The little clinical success of therapeutic cancer vaccines is generally attributed to the immunosuppressive tumor microenvironment at late-stage diseases. The administration of cancer-preventive vaccination at early stages, such as pre-malignant lesions or even in healthy individuals at high cancer risk could increase clinical efficacy by potentiating immune surveillance and pre-existing specific immune responses, thus eliminating de novo appearing lesions or maintaining equilibrium. Indeed, research focus has begun to shift to these approaches and some of them are yielding encouraging outcomes.

Genome Editing Strategies to Protect Livestock from Viral Infections

The livestock industry is constantly threatened by viral disease outbreaks, including infections with zoonotic potential. While preventive vaccination is frequently applied, disease control and eradication also depend on strict biosecurity measures. Clustered regularly interspaced palindromic repeats (CRISPR) and associated proteins (Cas) have been repurposed as genome editors to induce targeted double-strand breaks at almost any location in the genome. Thus, CRISPR/Cas genome editors can also be utilized to generate disease-resistant or resilient livestock, develop vaccines, and further understand virus–host interactions. Genes of interest in animals and viruses can be targeted to understand their functions during infection. Furthermore, transgenic animals expressing CRISPR/Cas can be generated to target the viral genome upon infection. Genetically modified livestock can thereby reduce disease outbreaks and decrease zoonotic threats.