Search Results (212)

Highly pathogenic avian influenza (HPAI) remains a persistent threat to global poultry production and public health. Current vaccine platforms show limited cross-clade efficacy and often fail to induce mucosal immunity. Recent advances in microbiome research reveal critical roles for gut commensals in modulating vaccine-induced immunity, including enhancement of mucosal IgA production, CD8⁺ T-cell activation, and modulation of systemic immune responses. Engineered commensal bacteria such as Lactococcus lactis, Bacteroides ovatus, Bacillus subtilis, and Staphylococcus epidermidis have emerged as promising live vectors for antigen delivery. Postbiotic and synbiotic strategies further enhance protective efficacy through targeted modulation of the gut microbiota. Additionally, artificial intelligence (AI)-driven tools enable predictive modeling of host–microbiome interactions, antigen design optimization, and early detection of viral antigenic drift. These integrative technologies offer a new framework for mucosal, broadly protective, and field-deployable vaccines for HPAI control. However, species-specific microbiome variation, ecological safety concerns, and scalable manufacturing remain critical challenges. This review synthesizes emerging evidence on microbiome–immune crosstalk, commensal vector platforms, and AI-enhanced vaccine development, emphasizing the urgent need for One Health integration to mitigate zoonotic adaptation and pandemic emergence. Full article

Viral infections persistently challenge global health through immune evasion and zoonotic transmission. Dendritic cells (DCs) play a central role in antiviral immunity by detecting viral nucleic acids via conserved pattern recognition receptors, triggering interferon-driven innate responses and cross-presentation-mediated activation of cytotoxic CD8⁺ T cells. This study synthesizes DC-centric defense mechanisms against viral subversion, encompassing divergent nucleic acid sensing pathways for zoonotic DNA and RNA viruses, viral counterstrategies targeting DC maturation and interferon signaling, and functional specialization of DC subsets in immune coordination. Despite advances in DC-based vaccine platforms, clinical translation is hindered by cellular heterogeneity, immunosuppressive microenvironments, and limitations in antigen delivery. Future research should aim to enhance the efficiency of DC-mediated immunity, thereby establishing a robust scientific foundation for the development of next-generation vaccines and antiviral therapies. A more in-depth exploration of DC functions and regulatory mechanisms may unlock novel strategies for antiviral intervention, ultimately paving the way for improved prevention and treatment of viral infections. Full article

Helicobacter pylori (H. pylori) infection is a leading cause of gastritis, peptic ulcers, and gastric cancer, affecting more than half of the global population. Its persistence in the acidic gastric environment and its ability to evade host immunity present major treatment challenges. Although antibiotics remain the standard therapy, rising antimicrobial resistance has reduced treatment efficacy, prompting the search for alternative and adjunct approaches. Emerging therapies include probiotics, antimicrobial peptides (AMPs), and plant-derived compounds, which target H. pylori through membrane disruption, immunomodulation, or direct antimicrobial activity. Novel drug delivery systems and microbiota-sparing interventions are also being investigated. Additionally, vaccine development offers a promising strategy for long-term protection, though challenges related to antigenic variability and host-specific responses remain. Despite these advances, treatment variability and the limited clinical validation of alternatives hinder progress. A multifaceted approach integrating microbiome research, host–pathogen interactions, and new therapeutic agents is essential for future success. Full article

Therapeutic cancer vaccines are a new growth point of biomedicine with broad industrial prospects in the post-COVID-19 era. Many large international pharmaceutical companies and emerging biotechnology companies are deploying different tumor therapeutic cancer vaccine projects, focusing on promoting their clinical transformation, and the vaccine industry has strong momentum for development. Such vaccines are also the core engine and pilot site for the development of new vaccine targets, new vectors, new adjuvants, and new technologies, which play a key role in promoting the innovation and development of vaccines. Various therapeutic cancer vaccines, such as viral vector vaccines, bacterial vector vaccines, cell vector vaccines, peptide vaccines, and nucleic acid vaccines, have all been applied in clinical research. With the continuous development of technology, therapeutic cancer vaccines are evolving towards the trends of precise antigens, efficient carriers, diversified adjuvants, and combined applications. For instance, the rapidly advancing mRNA-4157 vaccine is a typical representative that combines personalized antigens with efficient delivery vectors (lipid nanoparticles, LNPs), and it also shows synergistic advantages in melanoma patients treated in combination with immune checkpoint inhibitors. In this article, we will systematically discuss the current research and development status and clinical research progress of various therapeutic cancer vaccines. Full article

Self-assembling protein nanocages (SAPNs) are distinct natural structures formed by the self-assembly of identical subunits, providing a highly efficient platform and a novel strategy for vaccine development and RNAi therapy. Their internal cavity allows for precise cargo encapsulation, while the externally modifiable surface supports multivalent antigen presentation, thereby enhancing stability, targeted delivery, and immune activation. In addition to serving as stable subunit vaccines with multivalent antigen display, SAPNs can be incorporated into mRNA vaccines (SAPN-RNA vaccines) by pre-fusing with the antigen. This strategy stabilizes secreted antigenic proteins with prolonged presentation to the immune system, and improves vaccine efficacy while reducing off-target effects and minimizing required doses. Additionally, SAPNs can overcome cellular uptake barriers, enhance DNA vaccine efficacy, and enable the co-delivery of antigens and adjuvants. Functionalization with adjuvants or targeting ligands further improves their immunostimulatory properties and specificity. The SAPN-RNAi strategy optimizes siRNA delivery by promoting lysosomal escape, enhancing targeted uptake, and protecting siRNA from degradation through SAPN encapsulation. This review examines the structural and functional properties of protein nanocages and their applications in vaccine design and RNAi delivery, emphasizing their synergistic effects, and exploring current progress, challenges, and future directions. In conclusion, SAPNs represent a versatile multifunctional platform with broad applicability across subunit, mRNA and DNA vaccines, adjuvant co-delivery, and RNAi therapeutics, with significant potential against viral infections. Full article

The emergence of complex and rapidly evolving pathogens necessitates innovative vaccine platforms that move beyond traditional methods. This review explores the transformative potential of next-generation vaccine technologies, focusing on the combined use of synthetic biology, nanotechnology, and systems immunology. Synthetic biology provides modular tools for designing antigenic components with improved immunogenicity, as seen in mRNA, DNA, and peptide-based platforms featuring codon optimization and self-amplifying constructs. At the same time, nanotechnology enables precise antigen delivery and controlled immune activation through engineered nanoparticles such as lipid-based carriers, virus-like particles, and polymeric systems to improve stability, targeting, and dose efficiency. Systems immunology aids these advancements by analyzing immune responses through multi-omics data and computational modeling, which assists in antigen selection, immune profiling, and adjuvant optimization. This approach enhances both humoral and cellular immunity, solving challenges like antigen presentation, response durability, and vaccine personalization. Case studies on SARS-CoV-2, Epstein–Barr virus, and Mycobacterium tuberculosis highlight the practical application of these platforms. Despite promising progress, challenges include scalability, safety evaluation, and ethical concerns with data-driven vaccine designs. Ongoing interdisciplinary collaboration is crucial to fully develop these technologies for strong, adaptable, globally accessible vaccines. This review emphasizes next-generation vaccines as foundational for future immunoprophylaxis, especially against emerging infectious diseases and cancer immunotherapy. Full article

Background: Brucellosis poses a significant public health challenge, necessitating effective vaccine development. Current vaccines have limitations such as safety concerns and inadequate mucosal immunity. This study aims to develop an FcRn-targeted mucosal Brucella vaccine by fusing the human Fc domain with Brucella’s multi-epitope protein (MEV), proposing a novel approach for human brucellosis prevention. Methods: The study developed a recombinant antigen (h-tFc-MEV) through computational analyses to validate antigenicity, structural stability, solubility, and allergenic potential. Molecular simulations confirmed FcRn binding. The vaccine was delivered orally via chitosan nanoparticles in murine models. Immunization was compared to MEV-only immunization. Post-challenge assessments were conducted to evaluate protection against Brucella colonization. Mechanistic studies investigated dendritic cell activation and antigen presentation. Results: Computational analyses showed that the antigen had favorable properties without allergenic potential. Molecular simulations demonstrated robust FcRn binding. In murine models, oral delivery elicited enhanced systemic immunity with elevated serum IgG titers and amplified CD4+/CD8+ T-cell ratios compared to MEV-only immunization. Mucosal immunity was evidenced by significant IgA upregulation across multiple tracts. Long-term immune memory persisted for six months. Post-challenge assessments revealed markedly reduced Brucella colonization in visceral organs. Mechanistic studies identified FcRn-mediated dendritic cell activation through enhanced MHC-II expression and antigen presentation efficiency. Conclusions: The FcRn-targeted strategy establishes concurrent mucosal and systemic protective immunity against Brucella infection. This novel vaccine candidate shows potential for effective human brucellosis prevention, offering a promising approach to address the limitations of current vaccines. Full article

Vaccines remain one of the most effective tools in combating infectious diseases, though traditional platforms are constrained by limitations including suboptimal immunogenicity, safety concerns, and manufacturing complexity. Circular RNA (circRNA) vaccines have recently emerged as a novel vaccine modality, demonstrating unique advantages including high stability, low innate immunogenicity, and sustained antigen expression. Although early research has predominantly focused on viral targets, accumulating evidence now supports the application potential of circRNA vaccines against diverse pathogens, particularly antibiotic-resistant bacteria. Through encoding critical antigens or virulence factors, these circRNA vaccines demonstrate capability to induce protective immune responses, presenting a viable alternative to conventional antimicrobial strategies. This review highlights recent advances in circRNA vaccine development, spanning synthetic circularization techniques, delivery approaches, and immunological mechanisms. We emphasize their potential against viral, bacterial, fungal, and parasitic infections, while addressing current challenges and future research directions of this emerging platform. Collectively, these insights underscore circRNA’s multifaceted versatility and its expanding relevance in next-generation vaccine innovation. Full article

The activation of immunosuppressed antigen-presenting cells (APCs) in the tumor microenvironment is a key goal in modern cancer immunotherapy. Our laboratory utilizes a liposome-based immunotherapy platform that binds endogenous complement to deliver antigen, adjuvant, and therapeutic agents to APCs in vivo. The liposomes contain external linker groups, which readily bind complement protein C3, and mediate liposomal uptake via complement receptor 3 into APCs. To test the ability of a model antigen to bind to these external linker groups on C3-liposomes and elicit a robust adaptive immune response, we conjugated a modified ovalbumin peptide (OVA-C) to the liposomes and incorporated a toll-like receptor (TLR) 4 agonist, monophosphoryl lipid A (MPLA), in the liposomal membrane. Adaptive immune responses from C57BL/6 mice were analyzed by ELISA and ELISpot. Mice vaccinated with OVA-C liposomes elicited significantly greater humoral and cellular adaptive responses relative to controls. Furthermore, female mice vaccinated with MPLA + OVA-C liposomes produced significantly more IgG antibodies than males vaccinated with the same liposomes. In conclusion, antigen binding on the exterior of C3-liposomes markedly improves antigen loading efficiency and still allows for complement C3-targeted delivery to APCs. These data demonstrate the initiation of a robust cellular and humoral immune response using a new liposomal delivery platform. Full article

Background: Enteric disease caused by Shigella, Campylobacter, and enterotoxigenic Escherichia coli (ETEC) represents a significant global health burden, particularly among children in low-resource settings. However, no licensed vaccines are currently available for these bacterial pathogens. Given the wide range of enteric pathogens and the constraints posed by an increasingly crowded infant immunization schedule, the development of combination vaccines or combined administration of individual oral vaccines may offer a practical approach to address this unmet need. Objectives: In this study, we evaluated the combined administration of two multicomponent oral vaccine candidates: ETVAX, targeting ETEC, and a trivalent whole-cell vaccine targeting Shigella. Methods: The vaccine candidates were administered orally in mice, both individually and in combination, with and without the inclusion of the double-mutant heat-labile toxin (dmLT) adjuvant. Results: The results demonstrated systemic and intestinal-mucosal immune responses to the key protective antigens following both individual and combined vaccine administration. Importantly, the combination of the two vaccines did not compromise the elicitation of specific antibody responses. The inclusion of dmLT as an adjuvant significantly enhanced immune responses to several antigens, highlighting its potential to improve vaccine efficacy. Conclusions: These findings underscore the feasibility of combining ETEC and Shigella vaccine candidates into a single formulation without compromising immunogenicity. This combined approach has the potential to provide broad protective coverage, thereby mitigating the global impact of enteric diseases and streamlining vaccine delivery within existing childhood immunization programs. Our results support further development of this combination vaccine strategy as a promising tool in combating enteric infections and improving health outcomes, particularly among young children in endemic regions who are vulnerable to enteric disease. Full article

The development of effective vaccines requires a rational design that considers the interaction between antigens, their vectors, and the immune system in addition to the activation of pathways that induce a safe and specific immune response. The efficacy of a vaccine formulation depends on the nature of the antigen, the protection offered by the delivery system, the ability to potentiate the immune response, and the precise release of the immunogen. Carrier systems such as lipid nanoparticles, polymers, exosomes, and microorganisms can be functionalized by chemical, physical, or biological methods to generate selective and improved biodistribution profiles. These methods enhance interaction with target cells, thereby improving immunological efficacy. The conjugation of specific ligands or the modification of parameters such as shape, charge, and size of vectors can enhance the specificity, stability, and efficiency of antigen transport to cellular compartments, thereby facilitating a robust immune response. This study examines modifications in vaccine delivery systems, focusing on biomolecules and physicochemical changes that enhance antigen presentation. Additionally, we examine innovative methods, including microneedles, electroporation, and needle-free systems that show potential for enhancing the immune response. Full article

Salmonella enterica serovar Typhi (S. Typhi) produces outer membrane vesicles (OMVs) that remain comparatively underexplored as potential biotechnological tools. Here, we investigated how hypervesiculating S. Typhi mutants (ΔtolR and ΔdegS) can be engineered to load and deliver the fluorescent reporter protein mCherry, targeting human epithelial cells and the murine immune system. Deletions in tolR and degS led to distinct OMV phenotypes characterized by higher vesicle production and altered cargo composition, underscoring the impact of disrupted membrane integrity and envelope stress on OMV biogenesis. By fusing mCherry with the S. Typhi OmpA signal peptide (SP_ompA), we achieved robust and functionally intact intravesicular packaging in all strains. Flow cytometry and confocal microscopy revealed that the ΔtolR mutant exhibited particularly high cargo loading in the OMV fraction and pronounced mCherry delivery to epithelial cells, highlighting the potential of hypervesiculation to enhance OMV-based protein transport. However, immunization studies in mice showed that wild-type OMVs, despite carrying less mCherry than their hypervesiculating counterparts, induced the strongest anti-mCherry IgG responses. These findings indicate that, at least under these conditions, antigen loading alone is not sufficient to fully determine immunogenicity. Instead, the intrinsic composition or adjuvant-like properties of OMVs play a pivotal role in driving robust immune activation. Our results establish S. Typhi OMVs, especially when genetically modified with a Sec-dependent targeting signal (SP_ompA), as versatile platforms for heterologous protein delivery. Although hypervesiculation facilitates increased protein encapsulation and delivery to epithelial cells, native OMVs appear to better preserve and/or present antigens for effective immunogenic responses in vivo. These insights set the stage for further optimization of S. Typhi OMVs in vaccine development and protein therapeutics, where balancing cargo loading with immunostimulatory features may be key to achieving maximal efficacy. Full article

Vaccination remains the most effective strategy for preventing infectious diseases. Subunit vaccines, which consist of antigenic components derived from pathogens, offer significant advantages in terms of biosafety, ease of preparation, and scalability. However, subunit vaccines often exhibit lower immunogenicity than whole-pathogen vaccines do. To address this limitation, coupling antigens with nanoparticles has emerged as a promising strategy for enhancing immune responses by mimicking pathogen structures and improving antigen presentation. This study evaluated the stability of ferritin (F-nps) and encapsulin (E-nps) nanoparticles and their efficient uptake by bone-marrow-derived dendritic cells (BMDCs) in vitro. In vivo studies demonstrated their effective targeting of lymph nodes. The African swine fever virus C129R protein was conjugated to ferritin and encapsulin nanoparticles to assess its ability to enhance antigen-specific immune responses. In murine models, both F-nps and E-nps significantly increased the immunogenicity of the C129R antigen, highlighting their potential as effective vaccine delivery systems. These findings underscore the promise of ferritin and encapsulin nanoparticles as delivery platforms for enhancing antigen immunogenicity and pave the way for the development of nanoparticle-based vaccines. Full article

Background: Mucin-1 (MUC1) is a glycoprotein that is hypoglycosylated and overexpressed in most adenocarcinomas, making it a promising target for cancer vaccines. Our group previously demonstrated that C3 (OPSS)-liposomes enhance antigen uptake by antigen-presenting cells (APCs) via the complement C3 pathway and, when combined with toll-like receptor (TLR) agonists, reduce tumor growth in murine cancer models. Methods: In the present study, we evaluate the immunogenicity of MUC1 peptide vaccines encapsulated in C3-liposomes, with and without TLR agonists, using MUC1-tolerant transgenic mice challenged with Lewis lung carcinoma (LLC.MUC1) cells. To assess vaccine effectiveness, tumor volumes were measured, and flow cytometry and ELISA and ELISPOT assays were used to assess the immune response. Results: Both male and female C57BL/6 transgenic mice vaccinated with MUC1 C3-liposomes developed significantly smaller tumors than those vaccinated with free MUC1 peptide or PBS. Notably, a sex-dependent response emerged in mice vaccinated with MUC1 C3-liposomes with TLR agonists (TLR4, TLR7/8, and TLR9); male mice exhibited greater tumor suppression than females. Flow cytometry analysis revealed that female mice had significantly higher levels of CD11b⁺, LY6C⁺, and LY6G⁺ MDSC cells, suggesting a potential mechanism for the sex difference. Additionally, MUC1 C3-liposome vaccination elicited robust adaptive immune responses, including significantly higher levels of IFN-γ-producing T cells and MUC1-specific IgG antibodies compared to non-encapsulated MUC1 or TLR adjuvant-only formulations. Conclusions: These findings underscore the potential of C3-liposome-based antigen vaccines to enhance anti-tumor immunity and highlight the impact of sex differences in vaccine efficacy. Full article

Personalized cancer vaccines are a promising immunotherapy targeting patient-specific tumor neoantigens, yet their design and efficacy remain challenging. Recent advances in artificial intelligence (AI) provide powerful tools to enhance multiple stages of cancer vaccine development. This review systematically evaluates AI applications in personalized cancer vaccine research over the past five years, focusing on four key areas: neoantigen discovery, codon optimization, untranslated region (UTR) sequence generation, and mRNA vaccine design. We examine AI model architectures (e.g., neural networks), datasets (from omics to high-throughput assays), and outcomes in improving vaccine development. In neoantigen discovery, machine learning and deep learning models integrate peptide–MHC binding, antigen processing, and T cell receptor recognition to enhance immunogenic neoantigen identification. For sequence optimization, deep learning models for codon and UTR design improve protein expression and mRNA stability beyond traditional methods. AI-driven strategies also optimize mRNA vaccine constructs and formulations, including secondary structures and nanoparticle delivery systems. We discuss how these AI approaches converge to streamline effective personalized vaccine development, while addressing challenges such as data scarcity, tumor heterogeneity, and model interpretability. By leveraging AI innovations, the future of personalized cancer immunotherapy may see unprecedented improvements in both design efficiency and clinical effectiveness. Full article