Application Of Vaccines Research Articles

Development of a Novel Chimeric ND-GP cVLPs Vaccine for the Prevention of Goose-Derived Newcastle Disease and Gosling Plague

Goose-derived Newcastle disease (ND) and gosling plague (GP) are serious threats to the goose industry. Conventional vaccines have made significant contributions to preventing GP and ND. Nevertheless, the renewal of conventional vaccines and the application of novel vaccines are urgently needed to align with eco-friendly and efficient breeding concepts and achieve the final goal of epidemic purification. Therefore, based on the Newcastle disease virus-like particles (ND VLPs) vector platform, we developed novel chimeric ND-GP bivalent cVLPs (ND-GP cVLPs) displaying the NDV HN protein and the GPV VP3 protein. In vivo, immunization experiments revealed that geese immunized with 30 µg, 50 µg, or 70 µg of the ND-GP cVLPs and commercial vaccines produced highly effective hemagglutination inhibitory antibodies against NDV and neutralizing antibodies against GPV, respectively. Furthermore, 70 µg of the ND-GP cVLPs effectively protected against virulent NDV and GPV, reducing tissue damage from viral infection and virus shedding in the oropharynx and cloaca. In conclusion, we provide eco-friendly and efficient novel ND-GP cVLPs for preventing goose-derived ND and GP. Our findings provide the basis for using ND VLPs as foreign protein carriers for the developing of multi-conjugate vaccines.

Nanoparticles in Subunit Vaccines: Immunological Foundations, Categories, and Applications.

Subunit vaccines, significant in next-generation vaccine development, offer precise targeting of immune responses by focusing on specific antigens. However, this precision often comes at the cost of eliciting strong and durable immunity, posing a great challenge to vaccine design. To address this limitation, recent advancements in nanoparticles (NPs) are utilized to enhance antigen delivery efficiency and boost vaccine efficacy. This review examines how the physicochemical properties of NPs influence various stages of the immune response during vaccine delivery and analyzes how different NP types contribute to immune activation and enhance vaccine performance. It then explores the unique characteristics and immune activation mechanisms of these NPs, along with their recent advancements, and highlights their application in subunit vaccines targeting infectious diseases and cancer. Finally, it discusses the challenges in NP-based vaccine development and proposes future directions for innovation in this promising field.

Glycoside-Mediated Enhancement of Stability in Aluminum Oxyhydroxide Nanoadjuvants during Freeze-Drying.

Aluminum-based adjuvants have been indispensable to vaccine potency. However, their effectiveness is difficult to maintain after freeze-drying, which limits the storage and application of aluminum-adjuvanted vaccines. In this study, the impact of freeze-drying on aluminum oxyhydroxide nanorods (AlOOH NRs) was investigated. Freeze-drying led to aggregation and resulted in the loss of the surface hydroxyl content of aluminum adjuvants. To alleviate freeze-drying-induced damage, the potency of different alkyl glycosides as protectants was further evaluated. It was demonstrated that the structural balance of the head and tail of a glycoside was more conducive to protecting AlOOH NRs from aggregation and loss of surface hydroxyl groups. These results underline the proper selection of protectants to protect adjuvants against functional defects caused by freeze-drying, which is important for the stability and efficacy of vaccines and biopharmaceutical products.

Advances in mRNA LNP-Based Cancer Vaccines: Mechanisms, Formulation Aspects, Challenges, and Future Directions

After the COVID-19 pandemic, mRNA-based vaccines have emerged as a revolutionary technology in immunization and vaccination. These vaccines have shown remarkable efficacy against the virus and opened up avenues for their possible application in other diseases. This has renewed interest and investment in mRNA vaccine research and development, attracting the scientific community to explore all its other applications beyond infectious diseases. Recently, researchers have focused on the possibility of adapting this vaccination approach to cancer immunotherapy. While there is a huge potential, challenges still remain in the design and optimization of the synthetic mRNA molecules and the lipid nanoparticle delivery system required to ensure the adequate elicitation of the immune response and the successful eradication of tumors. This review points out the basic mechanisms of mRNA-LNP vaccines in cancer immunotherapy and recent approaches in mRNA vaccine design. This review displays the current mRNA modifications and lipid nanoparticle components and how these factors affect vaccine efficacy. Furthermore, this review discusses the future directions and clinical applications of mRNA-LNP vaccines in cancer treatment.

MRNA Vaccines: a Powerful Tool in Cancer Treatment

Cancer has always been one of the difficult objects for people to conquer. It’s killed a lot of people over a long period of time. As time goes on, technology becomes more and more advanced, and people are not limited to previous cancer treatments, but continue to research and try to find more treatments. In recent years, mRNA vaccines have gradually entered our field of vision. Compared with conventional vaccines, it often has a more flexible structure that can be modified, safer delivery methods, and higher efficiency. Although functional beyond imagination, the lack of knowledge in this area has prevented the use of mRNA vaccines in the treatment of many cancers. Once the many limitations and problems of mRNA are successfully solved, it can not only greatly promote the development of cancer treatment, but also make modern medicine get a milestone. This review introduces the current research and development progress of mRNA vaccines, and discusses the structure, delivery and application of mRNA vaccines.

Virus-like Particles-Based Vaccine to Combat Neurodegenerative Diseases.

Neurodegenerative diseases are regarded as gradual, incurable conditions with an insidious onset. Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the most prevalent neurodegenerative diseases reported globally. Developing effective treatment strategies for neurodegenerative diseases has remained a primary objective and a huge challenge for researchers. The therapeutic medications that are now approved for the treatment of neurodegenerative diseases merely treat the symptoms; the underlying pathology is not addressed. Therefore, the emergence of novel disease-modifying therapeutic modalities such as immunotherapy has opened a new path in developing effective treatments for neurogenerative diseases. Compared to other types of subunit active vaccines, virus-like particles (VLPs) are considerably more immunogenic as they present dense and repetitive viral antigen epitopes on their surface, which can trigger both humoral and cell-mediated immune responses. They are also a much safer option than the traditional inactivated and live-attenuated vaccines since they are devoid of viral genomes and are, therefore, non-pathogenic and non-infectious. Researchers have turned their attention to VLPs as an active immunotherapy candidate for AD due to the lessons learned from the AN1792 trial. Studies have shown that they effectively induce anti-Aβ, anti-tau, and anti-α-Synuclein antibodies while avoiding T-cell-related immune reactions in animal models of AD and PD. This review compiles the findings of preclinical animal model studies and clinical investigations on VLP-based vaccines for neurogenerative diseases thus far. The technical limitations and potential difficulties associated with the future application of VLP-based vaccines in patients with neurodegenerative diseases have also been covered.

Spleen-Targeted mRNA Vaccine Doped with Manganese Adjuvant for Robust Anticancer Immunity In Vivo.

The successful application of mRNA vaccines in preventing and treating infectious diseases highlights their potential as therapeutic vaccines for cancer treatment. However, unlike infectious diseases, effective antitumor therapy, particularly for solid tumors, necessitates the activation of more powerful cellular and humoral immunity to achieve clinical efficacy. Here, we report a spleen-targeted mRNA vaccine (Mn@mRNA-LNP) designed to deliver tumor antigen-encoding mRNA and manganese adjuvant (Mn2+) simultaneously to dendritic cells (DCs) in the spleen. This delivery system promotes DC maturation and surface antigen presentation and stimulates the production of cytotoxic T cells. Additionally, Mn2+ codelivered in the system serves as a safe and effective immune adjuvant, activating the stimulator of interferon genes (STING) signaling pathway and promoting the secretion of type I interferon, further enhancing the antigen-specific T cell responses. Mn@mRNA-LNP effectively inhibits tumor progression in established melanoma and colon tumor models as well as in a model of tumor recurrence after resection. Notably, the combination of Mn@mRNA-LNP with immune checkpoint inhibitors further enhances complete tumor suppression and prolonged the overall survival in mice. Overall, this "All-in-One" mRNA vaccine significantly boosts antitumor immunity responses by improving spleen targeting and immune activation, providing an attractive strategy for the future clinical translation of therapeutic mRNA vaccines.

Genomic Analysis of Aeromonas salmonicida ssp. salmonicida Isolates Collected During Multiple Clinical Outbreaks Supports Association with a Single Epidemiological Unit.

Outbreaks of furunculosis cause significant losses in salmonid aquaculture worldwide. With a recent rise in antimicrobial resistance, regulatory measures to minimize the use of antibiotics in animal husbandry, including aquaculture, have increased scrutiny and availability of veterinary medical products to control this disease in production facilities. In such a regulatory environment, the utility of autogenous vaccines to assist with disease prevention and control as a veterinary-guided prophylactic measure is of high interest to the producers and veterinary services alike. However, evolving concepts of epidemiological units and epidemiological links need to be considered during approval and acceptance procedures for the application of autogenous vaccines in multiple aquaculture facilities. Here, we present the results of solid-state nanopore sequencing (Oxford Nanopore Technologies, ONT) performed on 54 isolates of Aeromonas salmonicida ssp. salmonicida sampled during clinical outbreaks of furunculosis in different aquaculture facilities from Bavaria, Germany, from 2017 to 2020. All of the performed analyses (phylogeny, single nucleotide polymorphism and 3D protein modeling for major immunogenic proteins) support a high probability that all studied isolates belong to the same epidemiological unit. Simultaneously, we describe a cost/effective method of whole genome analysis with the usage of ONT as a viable strategy to study outbreaks of other pathogens in the field of aquatic veterinary medicine for the purpose of developing the best autogenous vaccine candidates applicable to multiple aquaculture establishments.

Unlocking Intracellular Protein Delivery by Harnessing Polymersomes Synthesized at Microliter Volumes using Photo-PISA.

Efficient delivery of therapeutic proteins and vaccine antigens to intracellular targets is challenging due to generally poor cell membrane permeation and endolysosomal entrapment causing degradation. Herein, these challenges are addressed by developing an oxygen-tolerant photoinitiated polymerization-induced self-assembly (Photo-PISA) process, allowing for the microliter-scale (10µL) synthesis of protein-loaded polymersomes directly in 1536-well plates. High-resolution techniques capable of analysis at a single particle level are employed to analyze protein encapsulation and release mechanisms. Using confocal microscopy and super-resolution stochastic optical reconstruction microscopy (STORM) imaging, their ability to deliver proteins into the cytosol following endosomal escape is subsequently visualized. Lastly, the adaptability of these polymersomes is exploited to encapsulate and deliver a prototype vaccine antigen, demonstrating its ability to activate antigen-presenting cells and support antigen cross-presentation for applications in subunit vaccines and cancer immunotherapy. This combination of ultralow volume synthesis and efficient intracellular delivery holds significant promise for unlocking the high throughput screening of a broad range of otherwise cost-prohibitive or early-stage therapeutic protein and vaccine antigen candidates that can be difficult to obtain in large quantities. The versatility of this platform for rapid screening of intracellular protein delivery can result in significant advancements across the fields of nanomedicine and biomedical engineering.

Mechanisms and Clinical Applications of Virus-Based Cancer Vaccines

Over the past several decades, immunotherapy as a novel cancer treatment has made tremendous progress. Several categories of immunotherapy have emerged, all designed to stimulate the patients immune system to fight cancer. Cancer vaccines, specifically virus-based cancer vaccines, is a subcategory of immunotherapy that can trigger both innate and adaptive immune response by targeting tumor-specific and tumor-associated antigens. This review summarizes the mechanisms of different types of virus-based cancer vaccines, including inactivated/live attenuated/subunit vaccines, oncolytic virus vaccines, and viral vector vaccines. Furthermore, this review introduces the clinical applications of virus-based cancer vaccines, including oncolytic virus vaccine T-VEC against metastasized melanoma, and Pexa-Vec and PROSTVAC that are currently in clinical trials. Virus-based cancer vaccines have shown encouraging results in numerous studies in enhancing overall survival, relapse-free survival, and overall response rate among patients with solid tumors. This review underscores the necessity for future research aimed at improving the efficacy of virus-based cancer vaccines and investigating combination therapies with other immunotherapies to achieve optimal treatment outcomes.

Lameness in Adult Sheep and Goats in Greece: Prevalence, Predictors, Treatment, Importance for Farmers.

The present study refers to an extensive investigation of lameness performed countrywide in Greece, on 325 sheep and 119 goat farms. The specific objectives of this work were to present data on the occurrence of lameness on sheep and goat farms and to identify variables (including variables related to climatic factors) associated with the disorder on the farms. Farms were visited and animals on the farm were assessed for the presence of lameness; further, an interview was carried out with the farmer to obtain information regarding practices applied on the farm. Climatic variables at the location of each farm were derived from NASA research. The within farm prevalence rate varied from 0.0% to 25.0% in sheep flocks and from 0.0% to 30.0% in goat herds. The mean ± standard error (median (interquartile range)) within farm prevalence rate among sheep farms was 1.9% ± 0.2 (0.0% (0.0%)); among goat farms, it was 2.6% ± 0.5% (0.0% (0.0%)). Multivariable analysis for within farm prevalence of lameness revealed three significant predictors in sheep farms: application of vaccination against foot-rot, increased precipitation at the farm location and longer annual grazing period for sheep, and one in goat farms: increased precipitation at the farm location. Treatment of lameness involved mostly administration of antibiotics (on 104 farms); the antibiotics administered most often were lincomycin (on 69 farms) and oxytetracycline (on 33 farms). There was a tendency for higher median within farm prevalence of lameness among farms where no antibiotic administration was practiced. Finally, 6.2% of sheep farmers and 4.2% of goat farmers considered lameness as an important health problem for the animals, specifically the third and fifth most important problem on the respective farms.

Oligonucleotide-Linked Lipid Nanoparticles as a Versatile mRNA Nanovaccine Platform.

An effective delivery platform is crucial for the development of mRNA vaccines and therapeutics. Here, a versatile platform utilizing cholesterol-modified oligonucleotides (L-oligo) that bind to the mRNA within lipid nanoparticles (LNP), and enables the effective delivery of the mRNA into target cells is introduced. mRNA incorporated into LNPs via linkage with L-oligo, termed oligonucleotide-linked LNP (lnLNP), is superior in cellular uptake and transfection efficiency in target cells in vitro and in vivo, compared to the conventional LNP formulations. It is further applied lnLNP as an mRNA vaccine platform for SARS-CoV-2, demonstrating robust induction of neutralizing activity as well as polyfunctional SARS-CoV-2-specific T-cell response in vivo. The current strategy can be versatilely applied to different LNP platforms, for vaccine and therapeutic applications against various diseases, such as infections and cancers.

A-187 Program for Recognition of Patient Safety Cores in Diagnostic Services

Abstract Background Health services are complex and challenging structures, including diagnostic services. Therefore, it is everyone's responsibility to ensure patient safety. The scope of this study is to present the challenges and opportunities in structuring the Quality Management and Patient Safety System (QM&PS) of a large diagnostic service that culminated in the first laboratory to receive the Patient Safety Core Recognition Seal (NSP), a program established by the partnership of QGA (Quality Global Assurance) and IBSP (Brazilian Institute for Patient Safety). Methods The restructuring of the QM&PS began in 2018 and since then, 6 NSPs have been established, distributed across 6 regions of the Brazil, with procedures, regulations, confidentiality agreements, and responsibilities clearly defined. The NSP are multidisciplinary and discuss 13 safety indicators monthly, namely: adverse events, contrast extravasation, falls and faints, reactions to medications, contrasts, and vaccines, immunization errors - vaccine application and exchange, loss of noble samples, technovigilance, and pharmacovigilance. With an engaged and participative Medical Board, the Patient Safety Committee was created in 2020, with the participation of top management and representatives of strategic leaderships to discuss cases of serious adverse events and deaths with systemic outputs and plans. In 2022, we conducted the first Patient Safety Perception Survey, from which we extracted insights to further develop the safety culture. Six working groups were organized focusing on interaction between company committees and programs, institutional communication for sharing information and Patient Safety initiatives in the organization, identification, prevention, and monitoring of incidents, risk management tool for analysis of clarity, application, and relevance of use as support for management and continuing education. Results The working groups involved 58 professionals and resulted in 65 implemented actions. Among the main results achieved, we can highlight the implementation of the rapid response flow to SAE (serious adverse event), Just Culture Policy, Disclosure Protocol, Second Victim Care Flow, Safety Rite in Customer Service Units, Patient Safety Trail, Institutional Communication, and the Patient Safety Core Recognition Seal. Conclusions Patient Quality and Safety must be part of the institutional pillar, composing the Strategic Objectives to be achieved. It is necessary to engage the organization and rely on the involvement of leadership and physicians. As a large service, our biggest challenges are demonstrating the effectiveness of implemented improvement actions in the face of identified risk modifications, defining strategies to reduce underreporting, and being able to involve all collaborators and operational teams in the safety culture.

COVID-19 Vaccine mRNA Biodistribution: Maternal and Fetal Exposure Risks.

SARS-CoV-2 infection during pregnancy has severe consequences on maternal and neonatal health. Presently, vaccination stands as a critical preventive measure for mitigating infection-related risks. Although the initial clinical trials for the COVID-19 vaccines excluded pregnant women, subsequent investigations have indicated mRNA vaccinations' effectiveness and short-term safety during pregnancy. However, there is a lack of information regarding the potential biodistribution of the vaccine mRNA during pregnancy and lactation. Recent findings indicate that COVID-19 vaccine mRNA has been detected in breast milk, suggesting that its presence is not confined to the injection site and raises the possibility of similar distribution to the placenta and the fetus. Furthermore, the potential effects and responses of the placenta and fetus to the vaccine mRNA are still unknown. While potential risks might exist with the exposure of the placenta and fetus to the COVID-19 mRNA vaccine, the application of mRNA therapies for maternal and fetal conditions offers a groundbreaking prospect. Future research should leverage the unique opportunity provided by the first-ever application of mRNA vaccines in humans to understand their biodistribution and impact on the placenta and fetus in pregnant women. Such insights could substantially advance the development of safer and more effective future mRNA-based therapies during pregnancy.

Poly(β-amino ester) polymer library with monomer variation for mRNA delivery

Non-viral vectors for mRNA delivery primarily include lipid nanoparticles (LNPs) and polymers. While LNPs are known for their high mRNA delivery efficiency, they can induce excessive immune responses and cause off-target effects, potentially leading to side effects. In this study, we aimed to explore polymer-based mRNA delivery systems as a viable alternative to LNPs, focusing on their mRNA delivery efficiency and potential application in mRNA vaccines. We created a library of poly(β-amino ester) (PBAE) polymers by combining various amine monomers and acrylate monomers. Through screening this polymer library, we identified specific polymer nanoparticles (PNPs) that demonstrated high mRNA expression efficiency, with sustained mRNA expression for up to two weeks. Furthermore, the PNPs showed mRNA expression only at the injection site and did not exhibit liver toxicity. Additionally, when assessing immune activation, the PNPs significantly induced T-cell immune activation and were effective in the plaque reduction neutralization test. These results suggest that polymer-based mRNA delivery systems not only hold potential for use in mRNA vaccines but also show promise for therapeutic applications.

Harnessing Bacterial Membrane Components for Tumor Vaccines: Strategies and Perspectives.

Tumor vaccines stand at the vanguard of tumor immunotherapy, demonstrating significant potential and promise in recent years. While tumor vaccines have achieved breakthroughs in the treatment of cancer, they still encounter numerous challenges, including improving the immunogenicity of vaccines and expanding the scope of vaccine application. As natural immune activators, bacterial components offer inherent advantages in tumor vaccines. Bacterial membrane components, with their safer profile, easy extraction, purification, and engineering, along with their diverse array of immune components, activate the immune system and improve tumor vaccine efficacy. This review systematically summarizes the mechanism of action and therapeutic effects of bacterial membranes and its derivatives (including bacterial membrane vesicles and hybrid membrane biomaterials) in tumor vaccines. Subsequently, the authors delve into the preparation and advantages of tumor vaccines based on bacterial membranes and hybrid membrane biomaterials. Following this, the immune effects of tumor vaccines based on bacterial outer membrane vesicles are elucidated, and their mechanisms are explained. Moreover, their advantages in tumor combination therapy are analyzed. Last, the challenges and trends in this field are discussed. This comprehensive analysis aims to offer a more informed reference and scientific foundation for the design and implementation of bacterial membrane-based tumor vaccines.

OCORRÊNCIA DA FEBRE DO NILO EM EQUINOS NO BRASIL

West Nile Fever (WNF) is a zoonotic arbovirus caused by the West Nile Virus (WNV). It is a highly relevant topic in veterinary medicine in Brazil. It was first identified in Uganda in 1937 and the virus spread to Africa, Europe, the Middle East, Western Asia and Australia. In 1999, the virus reached the United States and has since spread throughout the Americas, becoming the arbovirus with the largest geographic distribution. The first signs of WNV in Brazil appeared in 1999, with positive results in birds and horses, with birds acting as sentinels for the disease. In 2014, the first human case was recorded in Piauí. As of 2018, cases in birds and horses have been confirmed in Espírito Santo. WNV, an RNA virus of the Flaviviridae family, is transmitted by the bite of mosquitoes of the Culex genus, and these mosquitoes become infected through infected birds during the viremic period. Birds are amplifying hosts and humans and horses are accidental hosts. In Brazil, climatic, environmental and socioeconomic characteristics contribute to the amplification of the virus. Diagnosis is made by demonstrating antiviral IgM by ELISA, or, post-mortem, with RT-PCR. Preventive measures involve the use of repellents and screens, in addition to the application of larvicides. In horses, the application of vaccines, although recommended, is not yet licensed in Brazil. This study analyzed the occurrence of West Nile Fever in horses in Brazil through a review of scientific articles. Searches were conducted in the Google Scholar, PUBMED and Scielo databases, published between 2004 and 2024. The research was supported by the following search criteria: “Nile Fever”, “equines” and “Brazil”, in Portuguese, and “West Nile Fever”, “horses” and “Brazil”, in English. It was found that horses are accidental or terminal hosts and, because it is little known, many times it is not reported or diagnosed, thus demonstrating the importance of further studies and dissemination of information about this disease.

Exploration of the immunologic characteristics of KIT/PDGFRA wild-type gastrointestinal stromal tumor and potential application of neoantigen vaccination.

Exploration of the immunologic characteristics of KIT/PDGFRA wild-type gastrointestinal stromal tumor and potential application of neoantigen vaccination.

A Novel Self-Amplifying mRNA with Decreased Cytotoxicity and Enhanced Protein Expression by Macrodomain Mutations.

The efficacy and safety of self-amplifying mRNA (saRNA) have been demonstrated in COVID-19 vaccine applications. Unlike conventional non-replicating mRNA (nrmRNA), saRNA offers a key advantage: its self-replication mechanism fosters efficient expression of the encoded protein, leading to substantial dose savings during administration. Consequently, there is a growing interest in further optimizing the expression efficiency of saRNA. In this study, in vitro adaptive passaging of saRNA is conducted under exogenous interferon pressure, which revealed several mutations in the nonstructural protein (NSP). Notably, two stable mutations, Q48P and I113F, situated in the NSP3 macrodomain (MD), attenuated its mono adenosine diphosphate ribose (MAR) hydrolysis activity and exhibited decreased replication but increased payload expression compared to wild-type saRNA (wt saRNA). Transcriptome sequencing analysis unveils diminished activation of the double-stranded RNA (dsRNA) sensor and, consequently, a significantly reduced innate immune response compared to wt saRNA. Furthermore, the mutant saRNA demonstrated less translation inhibition and cell apoptosis than wt saRNA, culminating in higher protein expression both in vitro and in vivo. These findings underscore the potential of reducing saRNA replication-dependent dsRNA-induced innate immune responses through genetic modification as a valuable strategy for optimizing saRNA, enhancing payload translation efficiency, and mitigating saRNA cytotoxicity.

Development of mRNA Lipid Nanoparticles: Targeting and Therapeutic Aspects.

Lipid nanoparticles (LNPs) have emerged as leading non-viral carriers for messenger RNA (mRNA) delivery in clinical applications. Overcoming challenges in safe and effective mRNA delivery to target tissues and cells, along with controlling release from the delivery vehicle, remains pivotal in mRNA-based therapies. This review elucidates the structure of LNPs, the mechanism for mRNA delivery, and the targeted delivery of LNPs to various cells and tissues, including leukocytes, T-cells, dendritic cells, Kupffer cells, hepatic endothelial cells, and hepatic and extrahepatic tissues. Here, we discuss the applications of mRNA-LNP vaccines for the prevention of infectious diseases and for the treatment of cancer and various genetic diseases. Although challenges remain in terms of delivery efficiency, specific tissue targeting, toxicity, and storage stability, mRNA-LNP technology holds extensive potential for the treatment of diseases.