Search Results (172)

RNA vaccines—comprising linear mRNA, self-amplifying RNA, and circular RNA (circRNA)—constitute a core next-generation platform for the prevention and control of viral diseases; among these, circRNA vaccines possess notable structural stability, yet their technical bottlenecks and application prospects in veterinary medicine have not been systematically reviewed. This review synthesizes current research on circRNA vaccine design, circularization strategies, translation mechanisms, delivery systems, and immunological outcomes, and compares their antiviral performance with that of linear mRNA vaccines. Owing to their covalently closed circular conformation, circRNA vaccines exhibit enhanced resistance to nucleases and superior thermal stability, enabling sustained transfection activity at ambient temperatures without reliance on strict cold chains; through cap-independent translation driven by internal ribosome entry sites or N⁶-methyladenosine modifications, and in conjunction with optimized circularization protocols and lipid nanoparticle carriers, circRNA vaccines elicit substantially higher antiviral IgG titers and durable antigen-specific T-cell memory relative to linear mRNA vaccines. These vaccines have been deployed against COVID-19, monkeypox, influenza, and livestock viral diseases, demonstrating strong adaptability to viral variants and compatibility with mucosal or needle-free administration routes. CircRNA vaccines are well suited for both emergency outbreak response and routine immunization programs; nevertheless, challenges persist, including low circularization efficiency for long sequences, elevated manufacturing costs, and inadequate quality control standards. Addressing these issues through improved production workflows and delivery technologies adapted to resource-limited settings will be critical to establishing circRNA vaccines as a pillar of livestock disease management and as a strategic reserve for emerging zoonotic threats. Full article

Keyhole limpet hemocyanin (KLH) is a large copper-containing glycoprotein derived from the marine gastropod Megathura crenulata. Originally functioning as an oxygen transport molecule, KLH has gained considerable attention in biomedical research due to its exceptional immunogenic and immunostimulatory properties. Its complex quaternary structure, extensive glycosylation, and xenogeneic origin contribute to its ability to induce robust humoral and cellular immune responses in mammals without significant toxicity. These characteristics have established KLH as one of the most widely used carrier proteins in vaccine development and as a valuable model antigen for the investigation of adaptive immune responses. This review summarizes current knowledge on the biological origin, molecular structure, biosynthesis, and post-translational processing of KLH, with particular emphasis on its unique glycan architecture and its contribution to immunogenicity. Advances in glycomic and structural analyses have revealed an extraordinary diversity of N-linked glycans that distinguish KLH from mammalian glycoproteins and play a central role in immune recognition. The review further discusses methods for KLH isolation, purification, and characterization, as well as its application in experimental and clinical immunology as a standardized tool for assessing antigen-specific immune responses. In addition, the therapeutic and translational potential of KLH is examined across multiple biomedical fields. Particular attention is given to its use as a carrier protein in conjugate vaccines, its role in cancer immunotherapy, and its emerging applications in the development of vaccines and immunotherapeutic strategies targeting neurodegenerative diseases, atherosclerosis, and substance use disorders. Collectively, the available evidence highlights KLH as a unique marine-derived biomolecule that bridges glycobiology, immunology, and translational medicine, and continues to serve as an important platform for the development of next-generation immunotherapeutics and vaccine technologies. Full article

Mpox has emerged as a global public health concern, highlighting the limitations of traditional vaccinia-based vaccination strategies and the urgent need for precision vaccinology approaches. Advances in structural virology and immunoinformatics have enabled the identification of conserved immunodominant antigens from both mature virion and extracellular virion forms, supporting the development of multivalent antigen combinations capable of inducing broad neutralizing antibody (nAb) responses. Emerging delivery technologies including mRNA-lipid nanoparticles, viral vectors, and self-assembling protein nanoparticles offer rapid scalability, enhanced immunogenicity, and improved safety compared with conventional live-attenuated vaccines. Addressing antigenic evolution, vaccine supply limitations, and population-specific immune variability will be crucial for optimizing vaccine effectiveness. This review synthesizes current evidence on antigen design, vaccine delivery platforms, and immunological correlates of protection to outline a framework for next-generation mpox vaccines. Precision vaccinology therefore represents a transformative strategy for developing durable, clade-specific mpox vaccines and strengthening preparedness against future orthopoxvirus outbreaks worldwide. Full article

Seasonal influenza remains a major global public health challenge despite decades of vaccine development, underscoring the need for more effective and adaptable immunization strategies. The recently approved mRNA-1010 vaccine represents a promising advance by applying messenger RNA technology to a pathogen characterized by continuous antigenic drift. Recent Phase 3 clinical trials conducted in support of regulatory review have demonstrated robust immunogenicity and superior protective efficacy against seasonal influenza compared with standard influenza vaccines in adults aged 50 years and older. However, increased reactogenicity, particularly among younger adults, together with the need for continued post-marketing safety surveillance, highlights the balance between enhanced immune responses and tolerability. Beyond seasonal influenza, mRNA-1010 provides a foundation for next-generation respiratory vaccines, including combination formulations targeting influenza, SARS-CoV-2, and respiratory syncytial virus (RSV), while illustrating the broader potential of mRNA vaccine technology. At the same time, challenges related to manufacturing scalability, cost, cold-chain requirements, and global accessibility remain important considerations for widespread implementation. This perspective examines whether mRNA-1010 represents an incremental advance in influenza vaccination or a potential transformative milestone in respiratory immunization, while considering the continuing roles of alternative vaccine platforms in achieving optimal effectiveness, safety, and equitable global access. Full article

Non-communicable diseases (NCDs), including cancer, cardiovascular, neurodegenerative, autoimmune, and allergic diseases, account for a significant amount of global morbidity and mortality. Chronic viral infections have not been recognized as NCDs, despite the availability of several therapeutic vaccination strategies against oncogenic viruses, such as the hepatitis B virus (HBV) and the human papillomavirus (HPV). Indeed, chronic viral infection leads to the development and progression of malignancies directly linked to the viruses. These considerations support a connection between NCDs, infectious diseases, and therapeutic vaccination. Recent advances in technology have paved the way to the use of vaccines beyond the prevention of infectious diseases, heralding innovative therapeutic and preventative strategies for a variety of chronic NCDs. Here we will review the state of the art of personalized vaccine strategies for NCDs, with an emphasis on the diverse technological platforms used to develop them, including mRNA and DNA vaccines, viral vectors, dendritic cell-based vaccines, nanoparticle delivery systems, and next-generation adjuvants. The review intends to make the case for personalized and antigen-specific vaccination strategies as a compelling option for precision immunotherapy primarily in oncology, where neoantigen-based vaccines are being developed. In addition, we will also review tolerogenic vaccination strategies, vaccination strategies targeting pathological proteins and pathways in neurodegenerative and cardiovascular diseases, and vaccine-based treatment of chronic viral infections. Current evidence about vaccines suggests that several ways are available to induce an immune response or create tolerance to a disease, and possibly altering its course instead of simply controlling the symptoms. However, many challenges are still to be overcome, including disease variability, how to identify appropriate target antigens, the complexity of manufacturing process, long-term safety, and integration with already established treatments. By virtue of the convergence of multiple fields—immunology, genomics, bioinformatics, and new delivery systems—precision vaccinology is gaining momentum. Thus, it is envisaged that personalized vaccines will be an increasingly essential component of future preventive and therapeutic approaches for non-communicable diseases. Full article

Orthopoxviruses are zoonotic DNA viruses of continuing public health importance, as highlighted by recent global mpox outbreaks. The high antigenic similarity among orthopoxviruses enables cross-reactive immune responses but complicates the development of serological diagnostic systems for serosurveillance, assessment of previous exposure, evaluation of vaccine-induced immunity, and species differentiation. This review summarizes current knowledge regarding the structure, biological functions, and diagnostic and vaccine potential of major orthopoxvirus recombinant antigens. Particular attention is given to the genomic organization of Orthopoxvirus, differences between intracellular mature virion (IMV) and extracellular enveloped virion (EV) forms, and the characteristics of key antigens, including A29, M1, H3, A35, and B6. Comparative phylogenetic analyses demonstrated a high degree of conservation among structurally important orthopoxvirus proteins while also identifying variable regions potentially relevant for differential diagnostics. Available evidence indicates that IMV-associated proteins are primarily involved in virus neutralization, whereas EV-associated antigens contribute mainly to limiting viral dissemination. Consequently, multicomponent antigen strategies combining IMV- and EV-associated proteins appear to provide the greatest potential for the development of effective serological assays and next-generation subunit vaccines. Overall, rational antigen selection should be based on integrated evaluation of structural, functional, and immunological properties to optimize orthopoxvirus diagnostic and vaccine platforms. Full article

The pet food industry is undergoing a significant transformation, driven by the growing trend of companion animal humanization and increasing concerns over the environmental sustainability of conventional protein and lipid sources. Consumers now seek diets that not only meet basic nutritional requirements but also offer preventive health benefits. Microalgae, including Arthrospira (Spirulina, a kind of cyanobacterium), Chlorella, Schizochytrium, and Euglena gracilis, have emerged as versatile biological platforms capable of addressing both functional and sustainability challenges. These microorganisms produce high-quality proteins, omega-3 long-chain polyunsaturated fatty acids (particularly docosahexaenoic acid, DHA), natural pigments, and immunomodulatory polysaccharides. This review synthesizes findings from peer-reviewed studies on the application of microalgae in pet nutrition, covering dogs, cats, and aquatic companion animals. We examine how algal ingredients influence gut microbiota, for instance, by enriching beneficial genera such as Turicibacter and Peptococcus, enhance vaccine responses and mucosal immunity, support cognitive function in aging pets, and contribute to weight management. Particular attention is given to Euglena gracilis and its paramylon (β-1,3-glucan), a pathogen-associated molecular pattern that engages the Dectin-1 pathway to train innate immunity and has demonstrated antiviral activity through host defense mechanisms. The review also surveys the patent landscape, highlighting trends in palatability enhancement, hypoallergenic formulations, and novel delivery formats. Key challenges remain, including ingredient standardization, safety validation, palatability optimization, and consumer acceptance. We outline a translational roadmap that prioritizes well-designed clinical trials in target species and processing methods that preserve bioactivity. Collectively, the evidence positions microalgae, and Euglena gracilis in particular, as promising candidates for next-generation functional pet foods that deliver health benefits alongside ecological sustainability. Full article

African swine fever virus (ASFV) causes African swine fever (ASF), a highly lethal disease in pigs. Vietnam has approved two ASF live-attenuated vaccines (LAVs), but their efficacy and safety remain controversial, and no reliable, highly effective commercial ASF vaccine is available yet. Humoral immunity plays an important role in protection against ASFV infection. However, there is still controversy regarding whether ASFV infection can induce antibodies with neutralizing activity. Antibody-dependent cellular cytotoxicity (ADCC), as an antibody-mediated protective mechanism, offers a novel perspective for screening protective ASFV antigens. This study evaluated five structural proteins (pCP312R, pA104R, pA151R, p17, and pF317L) as subunit vaccine candidates based on their ability to induce antibodies that inhibit viral replication and mediate ADCC. The recombinant proteins were expressed in Escherichia coli, purified, and used to immunize pigs. Immune sera collected two weeks after the third immunization were tested for their ability to inhibit ASFV replication in porcine alveolar macrophages (PAMs) using rASFV-Gluc/EGFP. ADCC activity was assessed using a stable HEK293T-p17 cell line as target cells and porcine peripheral blood mononuclear cells (PBMCs) as effectors, with cytotoxicity measured by lactate dehydrogenase release. All five recombinant proteins were successfully expressed and purified. Immunization with pCP312R, pA104R, p17, and pF317L induced the production of specific antibodies in pigs, but only anti-p17 antibodies significantly inhibited ASFV replication in PAMs. The p17 is highly conserved across different ASFV genotypes and is predicted to contain a transmembrane domain. Anti-p17 antibodies effectively mediated PBMCs to specifically kill target cells, demonstrating significant ADCC activity. Moreover, the HEK293T-p17 cell line was specifically recognized by anti-ASFV sera. These findings indicate that p17 is a dual-functional antigen capable of eliciting antibodies that both inhibit viral replication and mediate ADCC in vitro. Furthermore, we have developed an in vitro platform for screening protective ASFV antibodies based on viral inhibition and ADCC, providing candidate targets for the development of next-generation ASF subunit vaccines. Full article

RNA vaccines have emerged as an attractive platform for treating infectious diseases, cancer immunotherapy, and personalized medicine; however, their clinical success depends on multiple factors, including efficient, stable, and scalable delivery systems. Because RNA molecules are highly sensitive to factors such as enzymatic degradation, oxidation, poor cellular uptake, and limited endosomal escape, nanocarrier platforms play essential roles in protecting RNA cargo and enabling effective intracellular delivery. The biological performance of RNA nanocarriers depends on efficient cellular uptake, endosomal escape, intracellular RNA delivery, biodistribution, and immune modulation. Comparative assessment emphasizes that lipid nanoparticles remain the most clinically mature approach, while nanostructured lipid carriers, polymeric systems, and exosome-based nanocarriers provide multiple benefits for stability, targeted delivery, biocompatibility, and/or controlled release. Translational challenges involving GMP manufacturing, batch reproducibility, regulatory expectations, and scale-up are considered critical for effective nano-based RNA vaccine delivery and are elaborated in this review. Emerging advances such as pKa-tuned ionizable lipids, ligand-targeted systems, stimuli-responsive nanocarriers, circular and self-amplifying RNA platforms, artificial intelligence-guided formulation design, and needle-free delivery technologies may further expand the safety, accessibility, and therapeutic potential of RNA vaccines. In this review, we highlight next-generation nanocarrier systems for RNA vaccines, with an emphasis on novel nanocarrier RNA vaccine delivery systems. Additionally, we evaluate stability engineering approaches that currently limit global vaccine distribution and the future of the nanocarrier platforms for RNA vaccines. Full article

Recent advances in vaccinology have accelerated the shift from conventional live-attenuated and inactivated vaccines toward subunit and nucleic acid-based platforms. Although these next-generation vaccines offer improved safety, rapid adaptability, and manufacturing flexibility, their relatively low intrinsic immunogenicity often requires efficient adjuvants and delivery systems. Nanoparticle-based vaccine platforms have therefore emerged as versatile tools capable of protecting antigens, improving targeted delivery, and modulating both innate and adaptive immune responses. This review summarizes the major classes of nanovaccine platforms, including lipid and polymeric nanoparticles, self-assembling protein nanostructures such as virus-like particles and ferritin nanocages, saponin-based self-assembling complexes, and inorganic nanomaterials. Particular attention is given to how vaccine performance is determined not only by material composition but also by nanoparticle physicochemical properties, biodistribution, cellular uptake, and mechanisms of immune activation. We further discuss the major challenges limiting clinical translation, including scalable manufacturing, safety evaluation, quality control, regulatory requirements, and long-term biocompatibility. Finally, emerging strategies involving hybrid and personalized nanovaccine platforms are highlighted, illustrating how nanotechnology and immunoengineering are transforming vaccine development for both prophylactic and therapeutic applications. Full article

Messenger RNA-lipid nanoparticle (mRNA-LNP)-based drug products represent a promising platform for prophylactic and therapeutic applications. However, their limited stability poses significant challenges for storage and global distribution. The instability of mRNA-LNP products makes them dependent on ultra-cold chain systems. This instability is driven by various physicochemical factors, including temperature, pH, light exposure, oxidation, aggregation, shear stress, and humidity. These factors destabilize the physical and chemical integrity of both mRNA and lipid nanoparticle (LNP) components, leading to reduced vaccine potency and potentially increasing the risk of adverse safety outcomes. Understanding these factors and their mechanisms is crucial for retaining mRNA-LNP efficacy. This review discusses the key physicochemical instability factors and molecular degradation mechanisms responsible for the structural and functional deterioration of mRNA-LNP formulations. Further, we summarize the stabilization strategies and analytical methods used to detect and quantify the degradation of mRNA-LNP products. Addressing these challenges is critical for advancing next-generation nucleic acid-based drug products and LNP-based delivery systems. Full article

Feline panleukopenia is a highly contagious and often fatal disease in cats caused by the feline panleukopenia virus (FPV), a member of the Parvoviridae family. Despite the widespread use of vaccination, FPV remains a significant threat to both domestic and wild felid populations worldwide, particularly in young or unvaccinated animals. Effective vaccination strategies are therefore essential for controlling the disease and reducing mortality. Current vaccines, including modified live and inactivated vaccines, have demonstrated substantial efficacy in inducing protective immunity; however, several challenges remain, such as maternal antibody interference, vaccine failure, and safety concerns in certain animal populations. Recent advances in vaccine technology have spurred the development of next-generation FPV vaccines, including recombinant vectors, DNA vaccines, virus-like particle (VLP) vaccines, and novel delivery platforms. Among these, probiotic-based vaccine vectors have garnered growing interest due to their favorable safety profiles, mucosal immunogenicity, and suitability for oral administration. These systems may provide innovative approaches for inducing both systemic and mucosal immune responses against FPV. This review summarizes the current understanding of the immunological mechanisms underlying protection against FPV infection and discusses the progress made in FPV vaccine development. Furthermore, it highlights the major challenges associated with current vaccination strategies and explores emerging vaccine platforms, including probiotic vector-based vaccines, as promising tools for future disease control. Improved vaccine design and optimized immunization strategies will be crucial for enhancing the prevention of feline panleukopenia in the future. Full article

Respiratory mucosal vaccination can induce robust humoral and cellular immune responses, as well as effective mucosal immunity at the primary site of pathogen entry, and has been shown to provide superior protection against respiratory viral infections compared with traditional approaches. Among current vaccine technologies, mRNA vaccines offer unique advantages, including rapid development, flexible antigen design, and potent immunogenicity. However, efficient mucosal delivery of mRNA remains challenging due to biological barriers within the respiratory tract, including mucus clearance, limited cellular uptake, and instability during aerosolization. Furthermore, mRNA formulations intended for respiratory mucosal delivery require more stringent safety and tolerability profiles. Recent advances in nanoparticle engineering have accelerated the development of mRNA delivery systems optimized for respiratory mucosal immunization. This review aims to evaluate how nanoparticle engineering strategies can overcome respiratory mucosal barriers and improve the safety, stability, delivery efficiency, extrahepatic expression, and immunogenicity of mRNA vaccines and therapeutics. We summarize recent progress in engineered mRNA nanoparticle platforms for respiratory mucosal immunity, encompassing modified lipid nanoparticles (LNPs), polymer-based mRNA nanoparticles, and hybrid nanoparticle systems, including lipid-inorganic, polymeric hybrid, and lipid-extracellular vesicle (EV) nanoparticles. We further discuss optimization strategies for mucosal mRNA delivery, including the incorporation of appropriate adjuvants, the development of polyethylene glycol (PEG) alternatives, and advanced delivery approaches. Finally, we highlight current challenges and future directions for the rational design of next-generation mRNA nanoparticle platforms that can induce durable and broadly protective mucosal immunity against respiratory viral infections. Full article

Influenza viruses, due to their simple genomic structure and potent immunostimulatory capacity, have been extensively explored for applications in cancer immunotherapy and viral vector vaccine development. However, wild-type influenza viruses possess inherent risks of lethal pathogenicity and transmissibility, which limit their direct application. Special cold-adapted influenza strains have been widely used in live attenuated vaccines, which rely on specific amino acid mutations. With the advancement in synthetic biology and reverse genetics technologies, a variety of next-generation attenuated influenza virus have been developed, including genome-recoded viruses, miRNA-targeted viruses, viruses containing premature termination codons, and proteolysis-targeting recombinantviruses. This study systematically summarized the synthetic biology-based strategies for generating a next-generation method for the attenuated influenza virus, critically discussed the advantages and limitations of each strategy, and further analyzed their applications and challenges in cancer therapy and viral vector vaccine development. By synthesizing current research progress, this review aimed to provide a theoretical basis for constructing safer, more stable, and more controllable influenza virus engineering platforms, and to offer new insights for the design of attenuated influenza virus suitable for tumor therapy and novel vaccine delivery. Full article

DNA vaccines have emerged as a promising immunization platform, offering key advantages over conventional vaccine approaches, including superior stability, a favorable safety profile, rapid and flexible antigen design, and scalable manufacturing. However, their clinical efficacy has remained limited, primarily due to inefficient cellular uptake, poor endosomal escape, and degradation of the plasmid DNA within host cells. Recent advances have highlighted minicircle DNA (mcDNA) as a next-generation alternative to conventional plasmid vectors. mcDNA constructs are compact, backbone-free episomal vectors containing only the expression cassette, including the promoter, transgene, and polyadenylation signal, while lacking bacterial sequences such as antibiotic resistance genes and origins of replication. This reduced vector size reduced vector-driven innate immune activation and susceptibility to epigenetic silencing, thereby improving transfection efficiency and supporting more sustained transgene expression in both dividing and non-dividing cells. This review provides a comprehensive overview of mcDNA technology in the context of vaccine development, discussing its structural design and production principles, mechanistic advantages over conventional plasmid DNA, and current applications across infectious disease and cancer vaccine platforms. In addition, we explore recent delivery strategies to enhance mcDNA transfection and immunogenicity, summarize existing limitations that hinder translation into applications, and outline future directions to optimize mcDNA-based vaccine technologies. Full article