Vaccine Field Research Articles

An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responses.

The human immunodeficiency virus (HIV), responsible of the Acquired Immune Deficiency Syndrome (AIDS), continues to be a major global public health issue with any cure or vaccine available. The Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that is induced by interferons and plays a critical role in the immune response. ISG15 is a modifier protein that covalently binds to its targets via a reversible bond, a process known as ISGylation, which is the best-characterized activity of this protein to date. However, ISG15 can also interact with intracellular proteins via non-covalent binding or act as a cytokine in the extracellular space after secretion. In previous studies we proved the adjuvant effect of ISG15 when delivered by a DNA-vector in heterologous prime-boost combination with a Modified Vaccinia virus Ankara (MVA)-based recombinant virus expressing HIV-1 antigens Env/Gag-Pol-Nef (MVA-B). Here we extended these results evaluating the adjuvant effect of ISG15 when expressed by an MVA vector. For this, we generated and characterized two novel MVA recombinants expressing different forms of ISG15, the wild-type ISG15GG (able to perform ISGylation) or the mutated ISG15AA (unable to perform ISGylation). In mice immunized with the heterologous DNA prime/MVA boost regimen, the expression of the mutant ISG15AA from MVA-Δ3-ISG15AA vector in combination with MVA-B induced an increase in the magnitude and quality of HIV-1-specific CD8 T cells as well as in the levels of IFN-I released, providing a better immunostimulatory activity than the wild-type ISG15GG. Our results confirm the importance of ISG15 as an immune adjuvant in the vaccine field and highlights its role as a potential relevant component in HIV-1 immunization protocols.

Synthesis and Antiviral Efficacy of Pyrimidine Analogs Targeting Viral Pathways

AbstractTo date, viruses are known to cause chronic to acute pathogenesis. Nevertheless, antiviral drugs have been known for their medicinal applications for the last few decades to treat infections caused by these pathogens. Despite advancements in the field of vaccination and antiviral drugs, there is a need for a molecule that can eradicate or control viral infection without getting resistance from pathogens will be a real challenge. This review covers possible ways to treat viral infections with pyrimidine and its mimics compared to known antiviral drugs. A comprehensive study of the report accomplished synthetic routes of pyrimidine analogs and their target‐specific antiviral potential. The present review article covers literature from 2018 to 2022.

Tactics targeting circular mRNA biosynthesis.

Faced with the development of mRNA technology in the field of medicine and vaccine, circular mRNA (circmRNA) becomes a strong alternative to mRNA for its circular secondary structure and higher stability. At present, the synthesis of circmRNAs has been realized by ligating linear mRNA precursors and is limited by poor efficiency. To solve this challenge, this study started with ribozyme catalysis and enzymatic reaction to explore different circmRNA biosynthesis strategies. In terms of ribozyme method, by screening different group I intron self-splicing system sequences, the sequence from thymidylate synthase (Td) gene of phage T4 showed the highest ligation efficiency. In terms of enzyme method, with the help of 20-bp homologous arm, T4 Rnl 2 was determined as the ligation method with the highest ligation efficiency. By comparing the two ligation methods, the expression level of circmRNA ligated by T4 Rnl 2 was 86% higher than that ligated by Td ribozyme. Based on these ligation methods, the screening results of internal ribosome entry site (IRES) sequences showed that mud crab dicistrovirus IRES was an IRES sequence with high ribosome binding ability and could be widely used in circmRNAs for efficient and stable translation in mammalian cells. These results should provide positive guidance for the industrial production of circmRNAs and the development of mRNA vaccines. Eventually, circmRNAs could widely function in the field of biomedicine.

Iterative hypothesis testing in HIV vaccine research: moving towards success.

Iterative hypothesis testing in HIV vaccine research: moving towards success.

Health of Roma People living in marginalized Communities in Slovakia

Introduction. The biggest Roma communities reside in the eastern part of Slovakia in the regions of Presov and Kosice, whose share is 35-40%. While the atlas of Roma communities from 2019 indicates that about 440,000 Roma live in Slovakia, only 156,000 Roma registered in 2021. Moreover, more than half of them stated Roma nationality only as a second nationality. Due to the fear of discrimination, racism and hate speech 10-15% of Roma did not state their identity because they consider it more advantageous in their efforts to integrate into society. It is also assumed that a significant part of the Roma (12- 15%) living in the south of Slovakia have adopted the Hungarian nationality. Objectives. The main goal was to map and analyse the development of civilizational and infectious diseases in the Roma population, taking into account the social, economic and cultural status of the Roma in Slovakia. Methods: The data were analysed on the basis of available statistics and forecasts of the development of diseases in the allSlovak databases maintained by the NCZI SR and the Statistical Office of Slovak Republic. We compared the development of tuberculosis, hepatitis, diabetes, and the overuse of psychotropic substances, which often occur in marginalized Roma communities. Results: The results showed that although some diseases such as tuberculosis and hepatitis are decreasing along with the general average of registered diseases in the population, their highest occurrence in terms of the number of registered cases still occurs in Roma communities. Among Roma, the proportion of people addicted to psychotropic substances is increasing, the risk of infectious and civilizational diseases such as e.g. diabetes, asthma, obesity and cardiovascular diseases. Conclusion. With the decreasing quality of life of the Roma, the number of infectious and civilizational diseases also increases, therefore we recommend that comprehensive prevention, education in the field of vaccination and support for early diagnosis of diseases be implemented.

The ambiguous future of the COVID-19 pandemic in the presence of a vaccine.

The ambiguous future of the COVID-19 pandemic in the presence of a vaccine.

Drug-delivery research and much more: interview with Dan Peer.

Drug-delivery research and much more: interview with Dan Peer.

Drug Susceptibility Test and Analysis of Quinolone Resistance Genes in Mycoplasma hyopneumoniae Vaccine Strains and Field Isolates from China.

Enrofloxacin is a commonly used animal-specific drug in veterinary clinics. However, this drug has no epidemiological cutoff values (ECVs/ECOFFs) for Mycoplasma hyopneumoniae in CLSI and EUCAST. Defining the epidemiological cutoff values (ECOFFs) of enrofloxacine to Mycoplasma hyopneumoniae (M. hyo) can inform an early detection of bacterial resistance to better manage the resistance prevention and also help in establishing drug resistance breakpoints;. We determined the susceptibility breakpoint of M. hyo to enrofloxacin by the American Clinical and Laboratory Standards Institute (CLSI) standard method based on the PCR of vaccine strains and wild strains drug resistance genes;. Eighty strains of M.hyo isolated in Tibet were moderately sensitive (S) to tetracycline, florfenicol, spiramycin, erythromycin thiocyanate, tilmicosin, tiamulin, lincomycin, clindamycin, ofloxacin, enrofloxacin, gentamicin, amikacin, with MICs below 0.5 μg/mL. For vaccine 168L, RM48, and J strains, the susceptibility to the same antibacterial drugs was lower compared to the Tibetan isolates. The resistance of J strain to erythromycin thiocyanate was confirmed. Gene point mutation was confirmed in Quinolone Resistance Determining Regions (QRDR) of HNSH strain Topoisomerase IV subunit A, this finding is compared with the sequencing results of 168L strain reference sequence (Accession number: CP003131). Arg-Lys amino acid mutation (G921A and G1179A) was confirmed for the increase of MIC value involved in M.hyo to enrofloxacine;. The cut-off value of M.hyo to enrofloxacin was set as 1 μg/mLby ECOFFinder XL 2010 V2.1.

Tumor antigen-unbiased variable epitope library contains mimotopes with antitumor effect in a mouse model of breast cancer

Breast cancer is one of the leading causes of death that affects the female population worldwide. Despite advances in treatments and a greater understanding of the disease, there are still difficulties in successfully treating patients. Currently, the main challenge in the field of cancer vaccines is antigenic variability which can reduce antigen-specific T- cell response efficacy. The search for and validation of immunogenic antigen targets increased dramatically over the past few decades and, with the advent of modern sequencing techniques, permitting the fast and accurate identification of the neoantigen landscape of tumor cells, will undoubtedly continue to grow exponentially for years to come. We have previously implemented Variable Epitope Libraries (VEL) as an unconventional vaccine strategy in preclinical models and for identifying and selecting mutant epitope variants. Here, we used an alanine-based sequence to generate a 9-mer VEL-like combinatorial mimotope library G3d as a new class of vaccine immunogen. An in silico analysis of the 16,000 G3d-derived sequences revealed potential MHC-I binders and immunogenic mimotopes. We demonstrated the antitumor effect of treatment with G3d in the 4T1 murine model of breast cancer. Moreover, two different T cell proliferation screening assays against a panel of randomly selected G3d-derived mimotopes allowed the isolation of both stimulatory and inhibitory mimotopes showing differential therapeutic vaccine efficacy. Thus, the mimotope library is a promising vaccine immunogen and a reliable source for isolating molecular cancer vaccine components.

Current Immunotherapy Techniques for Cancer Treatment: A Scoping Review

Introduction: Immunotherapy, or the utilization of the immune system in fighting cancer, has been of interest as of late. Many different immunotherapy strategies exist, such as modifying T cells, generating cancer vaccines, as well as using chemokines, to elicit a strong anti-tumor response. As a strong emerging field in cancer research, this paper aims to conduct a scoping review to investigate the current research in immunotherapy targeting cancer and to summarize popular methods versus under-researched topics in the field. Methods: This scoping review follows PRISMA. Articles were found using MEDLINE, Scopus, and EMBASE, and were then screened using inclusion and exclusion criteria using the title and abstracts and then the full text. After the screening stage, papers chosen were categorized depending upon the authors’ main method of adapting the immune system to target cancer. Results: A total of 194 articles were included in this review. From the 194 articles, the method with the greatest amount of research in adapting the immune system to attack cancer are CAR-T cells, with 31 articles (16.0%). The second greatest category was cancer vaccines (28 articles; 14.4%), the third largest was other T cell-based immunotherapy strategies (25 articles; 12.9%) and the fourth largest was generating antibodies (24 articles; 12.4%). Other notable categories include cytokines and immune checkpoint inhibitors, while the smallest categories include bacteria, natural medicine, and nanoparticles. Discussion: The main fields of CAR-T cells, cancer vaccines, and antibodies commonly target tumor antigens involved in either tumor proliferation and progression or cancer invasion and metastasis. Further research is needed to demonstrate the strengths or limitations of using one immunotherapy technique over the other when it comes to inhibiting both of these cancer hallmarks. Furthermore, the review identifies multiple promising future avenues of immunotherapy that are currently less extensively investigated, such as adapting other immune cells, coupling immunotherapy techniques with nanoparticles, or using bacteria proteins to elicit a stronger immune response. Conclusion: This review aids in summarizing current focuses in the field of immunotherapy and provides future avenues and next steps for cancer research for new scientists pursuing a career in cancer research.

Concomitant inhibition of PPARγ and mTORC1 induces the differentiation of human monocytes into highly immunogenic dendritic cells

Monocytes can differentiate into macrophages (Mo-Macs) or dendritic cells (Mo-DCs). The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) induces the differentiation of monocytes into Mo-Macs, while the combination of GM-CSF/interleukin (IL)-4 is widely used to generate Mo-DCs for clinical applications and to study human DC biology. Here, we report that pharmacological inhibition of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) in the presence of GM-CSF and the absence of IL-4 induces monocyte differentiation into Mo-DCs. Remarkably, we find that simultaneous inhibition of PPARγ and the nutrient sensor mammalian target of rapamycin complex 1 (mTORC1) induces the differentiation of Mo-DCs with stronger phenotypic stability, superior immunogenicity, and a transcriptional profile characterized by a strong type I interferon (IFN) signature, a lower expression of a large set of tolerogenic genes, and the differential expression of several transcription factors compared with GM-CSF/IL-4 Mo-DCs. Our findings uncover a pathway that tailors Mo-DC differentiation with potential implications in the fields of DC vaccination and cancer immunotherapy.

Pandemic Preparedness among Big Energy Companies: Call to Research and Action.

The COVID-19 pandemic, as a global phenomenon, has affected all the working realities, worldwide, with the same issues. The aim of the present work is to assess the experiences of management and their preparedness during the pandemic among big companies, in particular, in the energy sector. Based on an overview of scientific evidence and grey literature, we found that big companies followed evidence-based decision-making practices and offered preparedness and information plans. Specifically, these plans contained recommendations and best practices to be followed to avoid the risk of infection in the workplaces, as well as in the field of epidemiological surveillance and vaccination. Nevertheless, many research efforts are required, and it is important that a large number of big companies and corporations address these challenges worldwide, adopting a new sustainable approach that includes both the productivity and health of the workers. A Call to Action was then issued in order to achieve evidence-based leadership to address current and future public health emergency scenarios.

Molecular characterization and antimicrobial susceptibility profiles of Thai Mycoplasma synoviae isolates

Mycoplasma synoviae (MS) infection is mainly controlled by pathogen-free flocks’ maintenance, medication in infected flocks, and vaccination in high-risk flocks. The effective control strategy requires convenient approach for detecting and differentiating MS strains and reliable drug susceptible evidence for deciding on reasonable antimicrobial usage. This study aimed to characterize the partial vlhA gene of nine Thai MS isolates circulated in chickens in 2020, to verify the PCR-RFLP assay for strain differentiation, and to determine the eight antimicrobial susceptibility profiles using microbroth dilution method. Based on sequence analysis of the partial vlhA gene, Thai MS isolates in 2020 were classified as types E and L with 19 and 35 amino acid lengths, respectively. The developed PCR-RFLP assay could detect and differentiate vaccine and Thai field strains. Most Thai MS isolates in this study were susceptible to tylosin, tylvalosin, tiamulin, doxycycline, oxytetracycline, tilmicosin, and lincomycin-spectinomycin at MIC50 values of 0.0391, 0.0098, 0.0781, 0.1563, 0.1563, 0.625 and 0.625 μg/mL, respectively; and resistance to enrofloxacin at MIC50 value of 10 μg/mL. In conclusion, this study revealed diagnostic assays for differentiating MS strains and the antimicrobial susceptibility profiles of Thai MS, which are necessary to design suitable MS control procedures for poultry flocks.

Satisfaction of Polish pharmacists with completed training in the field of qualification and vaccination against COVID-19

Introduction The coronavirus pandemic in Poland required quick responses. After the invention of the Covid-19 vaccine, the main strategic goal became to vaccinate as many Poles as possible in the shortest time. This required the involvement of all medical services, including pharmacists. Qualifications to perform full vaccination services were acquired during courses organized by the Center for Postgraduate Medical Education. Almost 9,000 pharmacists have acquired qualifications for vaccinations, not all of them have decided to provide them in pharmacies. The aim of the study was a preliminary analysis of pharmacists' satisfaction from completed qualification courses to perform the protective vaccination service against Covid-19. Material and methods The study in the form of an online questionnaire was conducted among 403 professionally active pharmacists who completed a qualification course to provide the Covid-19 vaccination service. The questions concerned, among others, the assessment of the content delivery and skills during the course, as well as the usefulness of the content in practice. The collected data was subjected to statistical analysis. Results The vast majority of the surveyed pharmacists, regardless of their work experience, were satisfied with the completed qualification courses. Pharmacists with more than 10 years of work experience rated the theoretical part of the course better than their younger colleagues. For the practical part, there were no differences between the groups. The majority of pharmacists assessed the method of transferring practical skills as good or very good and indicated the usefulness of the acquired content and skills in practice. Conclusions The courses organized by the Center for Postgraduate Medical Education turned out to be satisfactory in the opinion of Polish pharmacists. It seems important to look for factors affecting the lack of provision of the Covid-19 vaccination service by some qualified pharmacists

A REVIEW ON CANCER IMMUNOTHERAPY

Compared with previous standards of care (including chemotherapy, radiotherapy, and surgery), cancer immunotherapy has brought significant improvements for patients in terms of survival and quality of life. Immunotherapy has now firmly established itself as a novel pillar of cancer care, from the metastatic stage to the adjuvant and neoadjuvant settings in numerous cancer types. In this review article, we highlight how the history of cancer immunotherapy paved the way for discoveries that are now part of the standard of care. We also highlight the current pitfalls and limitations of cancer checkpoint immunotherapy and how novel research in the fields of personalized cancer vaccines, autoimmunity, the microbiome, the tumour microenvironment, and metabolomics is aiming to solve those challenges

A Multiplex PCR Assay for Differential Identification of Wild-type and Vaccine Strains of Mycoplasma gallisepticum

Mycoplasma gallisepticum (MG) can cause respiratory disease in chickens and result in serious economic losses in the chicken industry. The use of live vaccines has been a favorable option for the control of MG infection in multi-age commercial layers and broiler breeders. There are three live vaccines, including ts-11, 6/85, and F strain, that have been commonly used in various parts of the world, including South Korea. The definitive diagnosis of the infection, therefore, requires the differentiation of wild-type field strains of MG from the vaccine strains used. Thus, we aimed to develop a novel multiplex PCR assay to discriminate between vaccine strains (ts-11, 6/85, and F strain) and wild-type field strains of MG isolated from infected chickens. We designed four novel primer sets that are each specific to MG species, ts-11, 6/85, and F strain. The multiplex PCR assay using the primer sets differentially identified wild-type and vaccine strains of MG but did not detect other avian bacteria. The detection limit of this assay was 250 fg/μL of genomic DNA of each strain tested. In addition, this assay was applied to 36 MG strains isolated from chickens over the past 20 years in South Korea. As a result, the assay identified 22 wild-type strains and 14 vaccine strains. Consequently, the novel multiplex PCR assay can discriminate between vaccine and wild-type field strains of MG and could be a valuable tool for the diagnosis of MG infection in MG-vaccinated chicken flocks.

Trends in research related to vaccine and cancer prevention from 1992 to 2022: A 30-years bibliometric analysis

ABSTRACT Vaccines may play an important role in cancer prevention. This bibliometric study in the field of vaccine and cancer prevention is designed to evaluate key research advances, identify existing deficiencies, and provide reference for future investigations. A total of 2916 original articles published in English from 1992 to 2022 were extracted from the Web of Science core collection. America (1,277) and the National Cancer Institute (82) were the most productive country and institution in this field, respectively. Vaccine was not only the most co-cited journal but also the most influential. Garland SM was the most prolific author, and Bosch FX was the most influential co-cited author. The keywords “cervical cancer” had the highest frequency. “Nanovaccines,” “vaccine acceptance” and “coverage” were the new research hotspots in this field. Currently, although an increasing number of publications involve vaccine and cancer prevention studies, most of them are related to cervical cancer, and few other cancers, suggesting the need to investigate other cancer prevention vaccines. The promising research hotspots, such as nanovaccines, vaccine acceptance, and vaccine coverage should be the focus of investigation. The study provides the current status and trends in clinical research on vaccine and cancer prevention, enabling researchers to identify hotspots and explore new study directions. In the future, vaccines are expected to play a key role in multiple cancer prevention.

Perspective vaccines for emerging viral diseases in farm animals.

The world has watched the emergence of numerous animal viruses that may threaten animal health which were added to the perpetual growing list of animal pathogens. This emergence drew the attention of the experts and animal health groups to the fact that it has become necessary to work on vaccine development. The current review aims to explore the perspective vaccines for emerging viral diseases in farm animals. This aim was fulfilled by focusing on modern technologies as well as next generation vaccines that have been introduced in the field of vaccines, either in clinical developments pending approval, or have already come to light and have been applied to animals with acceptable results such as viral-vectored vaccines, virus-like particles, and messenger RNA-based platforms. Besides, it shed the light on the importance of differentiation of infected from vaccinated animals technology in eradication programs of emerging viral diseases. The new science of nanomaterials was explored to elucidate its role in vaccinology. Finally, the role of Bioinformatics or Vaccinomics and its assist in vaccine designing and developments were discussed. The reviewing of the published manuscripts concluded that the use of conventional vaccines is considered an out-of-date approach in eliminating emerging diseases. However, these types of vaccines are considered the suitable plan especially in countries with few resources and capabilities. Piloted vaccines that rely on genetic-based technologies with continuous analyses of current viruses should be the aim of future vaccinology. Smart genomics of emerging viruses will be the gateway to choosing appropriate vaccines, regardless of the evolutionary rates of viruses.

Экономический эффект от вакцинации как аргумент в разъяснительной работе по вакцинопрофилактике

There is no doubt about the economic effect of vaccination. However, the relevant assessments have not yet become a convincing argument for the need for vaccination. P u r p o s e o f t h e s t u d y . Based on the results of the inventory of the existing domestic and foreign experience in determining the economic effect of vaccination, identifying management problems in the relevant explanatory work, propose other approaches on how to calculate the economic effect of vaccination and how to use this argument in explanatory work on vaccination. M a t e r i a l s a n d m e t h o d s . A comparative analytical assessment of domestic and foreign experience in the field of calculating the economic effect of vaccination has been carried out. It is analyzed what place the economic effect of vaccination has in explanatory work of state bodies on vaccination. R e s u l t s . It has been established that the insufficient effectiveness of explanatory work on vaccination is largely the result of an incorrect delineation of functions at different levels of government (municipal, regional, federal). Unreasonably large tasks in this area are assigned to the municipal level, while the federal level, on the contrary, turned out to be actually unreasonably exempted from solving the substantive tasks in the field of explanatory work on vaccine prevention. The analysis of foreign and domestic experience in determining the economic effect of vaccination confirmed the significance of the results, calculations, and estimates. The necessity of presenting the results of the assessment of the economic effect of vaccination in a simpler and more understandable form is substantiated. For this purpose, an assessment was made of what can give the economy in value terms 25 years of additional human life, which he received in the 20th century thanks, according to experts, to vaccination. The calculation of GDP per capita (according to Rosstat for 2021, in purchasing power parity) for 25 years of extra human life due to vaccination was carried out. The need to consider the issue of the advisability of paying people for vaccination is substantiated. F i n d i n g s . It is necessary to reconsider the traditional approaches to assessing the economic effect of vaccination. State and municipal authorities should update the tasks in the field of vaccination in order to increase its effectiveness.

Lipid nanoparticle-based mRNA candidates elicit potent T cell responses.

The induction of a potent T cell response is essential for successful tumor immunotherapy and protection against many infectious diseases. In the past few years, mRNA vaccines have emerged as potent immune activators and inducers of a robust T cell immune response. The recent approval of the Moderna and the Pfizer/BioNTech vaccines based on lipid nanoparticles (LNP) encapsulating antigen-encoding mRNA has revolutionized the field of vaccines. The advantages of LNPs are their ease of design and formulation resulting in potent, effective, and safe vaccines. However, there is still plenty of room for improvement with respect to LNP efficacy, for instance, by optimizing the lipid composition and tuning LNP for specific purposes. mRNA delivery is known to be strongly dependent on the lipid composition of LNPs and the efficiency is mainly determined by the ionizable lipids. Besides that, cholesterol and helper lipids also play important roles in mRNA transfection potency. Here, a panel of LNP formulations was studied by keeping the ionizable lipids constant, replacing cholesterol with β-sitosterol, and changing the fusogenic helper lipid DOPE content. We studied the ability of this LNP library to induce antigen presentation and T cell proliferation to identify superior LNP candidates eliciting potent T cell immune responses. We hypothesize that using β-sitosterol and increasing DOPE content would boost the mRNA transfection on immune cells and result in enhanced immune responses. Transfection of immortal immune cell lines and bone marrow dendritic cells (BMDCs) with LNPs was studied. Delivery of mRNA coding for the model antigen ovalbumin (OVA-mRNA) to BMDCs with a number of LNP formulations, resulted in a high level of activation, as evidenced by the upregulation of the co-stimulatory receptors (CD40 and CD86) and IL-12 in BMDCs. The enhancement of BMDC activation and T cell proliferation induced by the introduction of β-sitosterol and fusogenic DOPE lipids were cell dependent. Four LNP formulations (C12-200-cho-10%DOPE, C12-200-sito-10%DOPE, cKK-E12-cho-10%DOPE and cKK-E12-sito-30%DOPE) were identified that induced robust T cell proliferation and enhanced IFN-γ, TNF-α, IL-2 expression. These results demonstrate that T cell proliferation is strongly dependent on LNP composition and promising LNP-mRNA vaccine formulations were identified.