Search Results (177)

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

A capillary-driven microfluidic electrical screening platform was developed using silver nanoparticle (AgNP)-decorated laser-patterned villous microstructures on a glass substrate for the analysis of H3N2-infected A549 cells. The device integrated nanosecond laser patterning, AgNP conductive thin-film formation, passive capillary transport, and direct electrical readout within a single microfluidic sensing structure. Villous-like arrays were fabricated using a 1064 nm IR pulsed laser at a fluence of 4.35 J/cm², with a repetition rate of 300 kHz, pulse overlap of 96.7% and scanning speed of 500 mm/s. The fabricated structures exhibited a diameter of 60 μm, height of 80 μm and interpillar pitches ranging from 30 to 90 μm. After AgNP deposition, the surface showed a dominant Ag content of 59.2%, confirming successful formation of conductive microstructured electrodes. The 30 μm pitch structure produced the highest current response of 22 μA at 1 V and the highest ΔI_norm of 0.053 after introduction of H3N2-infected A549 samples. Wettability and capillary transport were tunable by pitch, with contact angles (CAs) decreasing from 140° to 30° and flow velocities decreasing from 0.1 mm/s to 0.03 mm/s. Formalin-fixed H3N2-infected A549 cells were electrically distinguished from non-infected A549 controls over 10¹–10⁶ PFU/μL, with detectable responses down to 10¹ PFU/μL. These results demonstrate a label-free, self-driven, and fabrication-oriented microfluidic strategy for electrical screening of virus-associated cellular samples. Full article

The magnitude and quality of adaptive immune responses are fundamentally influenced by the efficiency of antigen presentation. Traditional vaccine platforms, such as live–attenuated or inactivated pathogens, although immunogenic, often present safety concerns. Conversely, subunit vaccines, despite being safer, generally exhibit poor immunogenicity due to inadequate delivery of antigens to professional antigen–presenting cells (APCs). To address this issue, the development of innovative delivery systems has become a pivotal strategy to overcome significant biological barriers, including extracellular antigen degradation, suboptimal lymph node targeting, and inefficient cross–presentation necessary for CD8+ T cell activation. This review systematically explores recent advancements in delivery technologies aimed at enhancing antigen presentation, encompassing rationally engineered nanocarriers and sophisticated biomimetic platforms. We first examine how nanoparticle properties like size, surface charge, and ligand density affect intracellular trafficking and the transition from MHC–II to MHC–I cross–presentation. Then, we explore bioinspired systems such as extracellular vesicles, virus–like particles, and cell–membrane–coated nanoparticles that utilize natural biological traits for enhanced targeting and immune modulation. Additionally, we review new physical delivery methods like microneedle arrays and in situ electroporation for direct, minimally invasive antigen delivery to dendritic cells. Lastly, we discuss the potential of these platforms in personalized cancer vaccines and combination immunotherapies. By combining insights from materials science, immunology, and bioengineering, these next–generation delivery tools could enhance antigen presentation and transform precision vaccination and immune intervention. Full article

Porcine enteric coronaviruses (PECs), including porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV), remain major causes of neonatal diarrhea, dehydration, mortality, and economic loss in swine production. Despite substantial progress in vaccine development, durable field protection is still inconsistent. In this narrative review, this narrative review synthesizes current knowledge on PEC vaccine design from three connected perspectives: antigenic breadth, mucosal immunity, and translational evaluation. The economic and virological context of PEC vaccine development is first summarized, including the recurrent production burden of PECs, coronavirus genome organization, structural proteins, and the central role of the spike protein in receptor engagement, membrane fusion, and neutralizing antibody induction. Key issues are then discussed, including how spike diversity, conformational stability, epitope accessibility, glycan shielding, and antigen matching influence protective breadth; why intestinal secretory IgA, mucosal immune-cell trafficking, local memory responses, and lactogenic immunity should be prioritized as biologically relevant endpoints; and how delivery route, adjuvant selection, and platform design shape response quality. Current evidence on recombinant protein, viral-vectored, nanoparticle, virus-like particle, probiotic, plant-derived, and mRNA-based approaches is compared with attention to both promise and current evidentiary and translational limitations. The available literature suggests that future progress in PEC vaccinology is likely to depend less on platform novelty alone than on integrated vaccine designs that align antigen selection, mucosal delivery, maternal–neonatal protection, heterologous challenge, manufacturability, and field applicability. Full article

Cancer vaccines represent a promising strategy in cancer immunotherapy by inducing tumour-specific immune responses. However, their clinical efficacy remains limited due to challenges in antigen selection, including the distinction between self and non-self-antigens, as well as issues related to antigen delivery, immune activation, and tumour immune evasion. Advances in nanotechnology have introduced innovative approaches to improve vaccine stability, targeted delivery, and immunogenicity. Nanoparticle-based platforms, including lipid, polymeric, inorganic nanoparticles, and virus-like particles, enable efficient delivery of tumour antigens and immunostimulatory adjuvants to antigen-presenting cells, thereby enhancing adaptive immune responses. Despite these advances, several translational challenges persist, including immunosuppressive tumour microenvironments, inefficient lymph node targeting, safety concerns, and manufacturing limitations. This review summarizes key nanoparticle platforms used in cancer vaccine development and discusses major barriers to their clinical translation. We also emphasize platform-selection criteria, cargo-dependent carrier design, nanoparticle size constraints, engineering strategies used to improve cytosolic delivery and endosomal escape, and the current clinical pipeline of cancer nanovaccines. Additionally, emerging strategies such as personalized nanovaccines, mRNA vaccine platforms, and combination immunotherapies are highlighted as promising approaches to improve therapeutic efficacy. These advances are expected to accelerate the clinical translation of nanotechnology-enabled cancer vaccines and support the development of next-generation cancer immunotherapies. Full article

This review systematically evaluates research on self-assembling protein nanoparticles (SPNPs)-based vaccine, focusing on three major categories: virus-like particles (VLPs), natural protein nanoparticles (e.g., ferritin and encapsulin), and computationally designed protein nanoparticles—with comparative analyses of their design strategies, immunogenicity, and applicability in next-generation vaccines. VLPs can elicit robust humoral and cellular immune responses due to their virus-mimetic structures. Natural protein nanoparticles provide excellent biocompatibility and controllable self-assembly for multivalent antigen presentation. Artificially designed protein nanoparticles allow precise structural optimization to facilitate tailored antigen display and immune modulation. Overall, SPNPs constitute a versatile and powerful platform for vaccine development. By integrating natural and engineered design principles, they offer new opportunities for rational vaccine design and the development of safer and more effective immunization strategies. Full article

Nipah virus (NiV) is an animal-borne RNA virus of the genus Henipavirus that poses a significant global health threat. This threat is driven by the virus’s high mortality rate, its capacity to cause epidemics, and the lack of licensed therapeutic interventions or vaccines. Since its initial identification during the 1998–1999 outbreak in Malaysia and Singapore, recurrent episodes have occurred primarily in Bangladesh and India, with mortality rates frequently exceeding 70%. Fruit bats of the genus Pteropus serve as the biological host for the virus. Transmission to humans occurs via contact with infected wildlife, consumption of contaminated products, such as freshly harvested date palm sap, or direct person-to-person exposure. Other modes of transmission, such as transplacentally or via breast milk, are still under investigation. The clinical presentation of NiV infection varies widely, from mild flu-like symptoms to life-threatening respiratory disease and acute encephalitis. It frequently attacks the nervous system, which can lead to coma, permanent neurological damage, or relapsing encephalitis. The virus enters host cells via ephrin-B2/B3 receptors, enabling systemic dissemination and infiltration of the central nervous system. Diagnosis relies primarily on RT-PCR and serological assays, and virus isolation requires high-containment laboratories. Management remains largely supportive, as no approved antiviral therapy exists. Experimental agents, such as remdesivir, favipiravir, and monoclonal antibodies such as m102.4, have shown promise in preclinical studies. Multiple vaccine platforms—including subunit, viral vector, mRNA, and nanoparticle-based approaches—are under development, though none is yet licensed for human use. Strengthened surveillance, infection control measures, and continued research are essential to mitigate the threat posed by this emerging pathogen. This review summarizes current knowledge on NiV, including its virology, epidemiology, pathogenesis, transmission, and recent progress in therapeutic and vaccine development. Full article

Controlled delivery using nanoparticle-based systems has attracted considerable attention; however, achieving cell-type specificity remains a major challenge. To address this issue, we focused on the intrinsic cell tropism of viruses. The hepatocyte tropism of hepatitis B virus (HBV) is mediated by interactions between its large envelope protein (L protein) and host factors, including the sodium taurocholate cotransporting polypeptide (NTCP). In this study, we explored viral-like secretory vesicles (VLSVs) displaying HBV spike proteins as a virus-inspired vesicle platform for hepatocyte targeting. We previously established a method for producing VLSVs from HBV L- and S-expressing HEK293T cells. In the present study, we developed an improved protocol using exosome-depleted fetal calf serum and optimized ultracentrifugation, resulting in VLSVs with comparable particle numbers and sizes but approximately tenfold higher protein content per particle. VLSVs were concentrated using a two-layer sucrose cushion, labeled with DiI, and purified by sucrose density gradient ultracentrifugation. We evaluated DiI uptake in hepatocyte-derived cells (HepG2 and Huh7), non-hepatic cells (MDA-MB231, H1299, HeLa, and Vero), and NTCP-overexpressing HepG2 cells. VLSVs showed preferential uptake in the following order: NTCP-overexpressing HepG2 > HepG2 > Huh7 > non-hepatic cells. Furthermore, removal of the N-terminal Flag tag from the L protein enhanced hepatocyte-associated uptake, suggesting the importance of preserving the native structure of the preS1 domain. While vesicle characterization and mechanistic validation remain to be further investigated, these findings provide a proof-of-concept for a virus-inspired vesicle platform exhibiting preferential uptake in hepatocyte-derived cells. Full article

Most infectious pathogens enter the host through mucosal surfaces, yet conventional injectable vaccines primarily induce systemic immunity without eliciting robust secretory immunoglobulin A (SIgA) responses at mucosal sites. The COVID-19 pandemic highlighted this limitation, as intramuscular mRNA vaccines failed to establish durable mucosal immunity in the upper respiratory tract. This review covers recent progress in mucosal vaccine development. We first discuss the organization of the mucosal immune system, focusing on SIgA induction, tissue-resident memory T (${\mathrm{T}}_{\mathrm{RM}}$) cells, and resident memory B (${\mathrm{B}}_{\mathrm{RM}}$) cells. We then examine mucosal adjuvants, from cholera toxin and heat-labile enterotoxin derivatives to stimulator of interferon gene (STING) agonists and a strategy to enhance alum adjuvanticity through neutrophil elastase inhibition. Delivery routes including intranasal, oral, and sublingual administration are reviewed alongside viral vectors, nanoparticles, mRNA-lipid nanoparticles, virus-like particles, and engineered bacterial platforms. The roles of innate immune cells, T helper cell subsets, and the microbiota in shaping vaccine responses are discussed. Finally, we survey licensed mucosal vaccines and the COVID-19 mucosal vaccine pipeline, analyze persistent barriers to clinical translation including the absence of validated mucosal correlates of protection, and outline future directions for thermostable formulations and systems biology-driven vaccine design. Full article

For over a decade, non-integrating Sendai virus vectors have been the gold standard for induced pluripotent stem cell (iPSC) reprogramming. However, as the field shifts toward regenerative and precision medicine and large-scale biorepositories, Sendai virus workflow necessitates dedicated viral-clearance testing, specialized manufacturing controls, and heightened regulatory oversight, leading to increased cost. While mRNA-based reprogramming offers a non-viral alternative, traditional mRNA delivery methods like electroporation are often physiologically disruptive. This study evaluates an mRNA-reprogramming platform that delivers lipid nanoparticles (mRNA-LNPs) via receptor-mediated endocytosis. By utilizing both Sendai virus and mRNA-LNP approaches to reprogram PBMCs from the same donor, we established a genetically identical starting point. Results demonstrate that mRNA-LNP-reprogrammed iPSCs maintain genomic integrity, retain the donor KCNH2 c.2398+5G>T variant, and exhibit characteristic colony morphology, pluripotency markers, and trilineage differentiation capacity consistent with the Sendai-reprogrammed counterparts. The mRNA-LNP-reprogrammed iPSCs differentiate into iPSC-derived cardiomyocytes presenting sarcomeric structures and electrophysiological activity, recapitulating a disease-specific phenotype. Notably, the mRNA-LNP workflow reached these milestones in significantly fewer passages than the Sendai virus workflow, markedly shortening timelines and reducing costs. These findings highlight mRNA-LNP reprogramming as a potentially attractive and effective, virus-independent platform to support future regenerative and precision medicine initiatives and scalable biobanking. Full article

Background: Despite the effectiveness of current SARS-CoV-2 vaccines, the genetic variability of the viral target has led to the emergence of variants capable of evading vaccine-induced protection. To ensure broader and more durable protection, we investigated the efficacy of a novel vaccine strategy. Methods: This vaccine utilizes the highly conserved nucleocapsid (N) protein as its primary antigen, rather than the spike (S) protein. It incorporates the Papaya Mosaic Virus (PapMV) nanoparticle, a Toll-like receptor (TLR) 7/8 agonist with intrinsic adjuvant properties, as a vaccine platform. Results: The vaccine formulations, comprising PapMV nanoparticles and the N antigen covalently or non-covalently attached to the PpaMV nano, generated robust humoral (antibody) and cellular (T-cell) immune responses. Protective efficacy was evaluated in K18-hACE2 transgenic mice challenged with either the ancestral SARS-CoV-2 strain or the Omicron XBB.1.5 variant. In both cases, the vaccine significantly reduced inflammation and viral titers in the lungs of vaccinated animals. Conclusions: These results highlight the potential of this PapMV-N vaccine to induce broad protection against diverse SARS-CoV-2 variants. Full article

Background: Rabies is a highly fatal zoonotic disease that causes approximately 59,000 human deaths worldwide each year. Current inactivated rabies vaccines require multiple doses and are associated with high costs. The full-length rabies virus glycoprotein (RVG), a membrane protein, exhibits substantial instability in its trimeric structure during recombinant expression. This instability makes it difficult to obtain high-purity, correctly folded antigens. Objectives: This study focuses on the preparation of a full-length recombinant RVG subunit vaccine candidate expressed in a glycoengineered Pichia pastoris system with mammalian-like glycosylation. Methods: The full-length RVG gene (including the transmembrane domain and cytoplasmic tail) from the Challenge Virus Standard-11 (CVS-11) strain was codon-optimized and inserted into the pPICZαA vector to construct the recombinant expression plasmid pPICZαA-RVG. The plasmid was transformed into glycoengineered Pichia pastoris X33-7 (low-mannose type) by electroporation for inducible expression. The target protein was purified by nickel affinity chromatography, anion-exchange chromatography, and Superdex-200 size-exclusion chromatography. The structural characteristics of the purified protein were analyzed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The purified antigen was formulated with the adjuvants AS03 or MF59. BALB/c mice (n = 5 per group) were immunized intramuscularly following a four-dose schedule (days 0, 7, 14, and 28). Antigen-specific IgG antibody titers were measured by ELISA, and neutralizing antibody titers were determined using the rapid fluorescent focus inhibition test (RFFIT). Results: Glycoengineered Pichia pastoris yeast strains expressing wild-type RVG (RVG-WT) or a mutant variant (RVG-M6: R84S, R199S, H270P, R279S, K300S, and R463S) were successfully constructed. The purified RVG antigen formed nanoparticles with an average particle size of approximately 75 nm. Immunized mice generated robust RVG-specific IgG responses, with titers reaching approximately 6.31 × 10⁵ for RVG-WT after the fourth immunization, compared to 3.16 × 10³ for RVG-M6 and 5.62 × 10³ for the RVG-WT-PEG control. Two weeks after the fourth immunization, RVG-WT formulated with AS03 or MF59 induced significant neutralizing antibody responses compared with the control group (p < 0.0001 and p < 0.01, respectively). The neutralizing antibody titers reached 1:79.43 in the AS03 group and 1:33.11 in the MF59 group, whereas the WT-PEG + AS03 control group showed a low titer of 1:3.72. In contrast, RVG-M6 formulated with MF59 failed to induce detectable neutralizing antibodies (1:3.02). Furthermore, RVG-WT + AS03 induced significantly higher neutralizing antibody responses than the WT-PEG + AS03 control group (p < 0.0001), and a significant difference was also observed between the RVG-WT + MF59 and RVG-M6 + MF59 groups (p < 0.01). Conclusions: The glycoengineered Pichia pastoris expression system successfully produced uniform full-length rabies virus glycoprotein nanoparticles with high purity. When formulated with the AS03 adjuvant, RVG-WT induced high-titer neutralizing antibodies in mice, suggesting a promising strategy for the development of recombinant subunit vaccines against rabies. However, this study is limited by the absence of challenge studies and validation in target animal species, which will be further investigated in future work. Full article

Background/Objectives: Pathogenic mammarenaviruses cause severe hemorrhagic and neurologic disease in humans. Machupo virus (MACV), a New World (NW) mammarenavirus, causes Bolivian hemorrhagic fever in humans, and there are no approved vaccines. Methods: Here, we describe and compare the immunogenicity of three vaccines expressing the MACV glycoprotein complex (GPC) in C57BL/6 mice: a recombinant vesicular stomatitis virus (rVSV) and two different lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA (mRNA-LNP) vaccines. The first mRNA-LNP vaccine, designated MACV mRNA, expresses the full-length MACV GPC. The second mRNA-LNP vaccine, called MACV VLP mRNA, encodes MACV GPC with appended sequences that induce the budding of virus-like particles (VLPs) with MACV GPC on the surface. This is the first description of any mRNA-LNP vaccine for MACV and the first comparison of mRNA and rVSVs as vaccine candidates for MACV. Results: We find that two doses of either MACV mRNA or MACV VLP mRNA are required for the induction of robust humoral and cellular immune responses including total MACV GPC IgG, neutralizing antibodies, cross-reactive antibodies that bind the related Junín virus GPC, and MACV-specific T-cell responses. To further investigate vaccination strategies for MACV, we also evaluated a heterologous prime-boost regimen involving the MACV mRNA vaccine coupled with the rVSV-based MACV vaccine. We find that the highest levels of MACV GPC-specific IgG and neutralizing titers were achieved when heterologous mRNA and rVSV prime-boost regimens were employed. Conclusions: These results elucidate differences in the immune response to different vaccine platforms for MACV and can inform future vaccine development for NW arenaviruses. Full article

Recent years have seen rapid progress in biological treatments for genetic diseases, as well as conditions like type 1 diabetes that lack an obvious genetic component. The authors sought to explain why this progress has emerged at this particular moment. The best way to illustrate this is by showcasing a wide range of therapies targeting diverse diseases. This progress has been driven by technological advances in genetically modified CAR-T and CAR-NK cells (e.g., using CRISPR or transgenes), which have led to significant improvements in cancer therapy. A key trend now is the emergence of “off-the-shelf” approaches aimed at generating cellular therapies compatible with a range of recipients by mitigating alloreactivity and immune rejection. Different diseases impose distinct biological and logistical limitations; thus, treatment of each patient requires an appropriate strategy. Emerging advances include the modification of therapeutic cells, either ex vivo or in vivo. Current options for transgene delivery mainly comprise lipid nanoparticles (LNPs), adeno-associated virus (AAV) vectors, and lentiviral vectors. Researchers also focus on selecting suitable promoters for specific expression in selected cell types. Altogether, these advances have led to remarkable progress in treating various diseases in recent years. This publication discusses the development of biological therapies, with particular emphasis on cell and gene therapies, illustrated by viable examples across various disorders. It covers implemented solutions for several types of cancer, as well as selected hereditary diseases and syndromes, including Huntington’s disease, carbamoyl phosphate synthetase 1 (CPS1) deficiency, hemiplegia, epidermolysis bullosa, chronic granulomatous disease, and congenital deafness. Emerging applications in heart diseases and diabetes are also summarized, along with therapeutic strategies involving tRNA gene editing. Although numerous strategies exist, only the most representative, practical, and up-to-date examples are emphasized. Full article

Background/Objectives: While CRISPR/Cas9 technology offers a revolutionary approach for correcting genetic ocular blindness, efficient and safe delivery remains the primary bottleneck. Traditional viral vectors, despite their efficacy, face challenges regarding cargo size limitations and potential genomic integration risks. Non-viral vectors offer distinct comparative advantages, including large cargo capacity for diverse CRISPR tools and transient expression to minimize off-target effects, but must overcome the eye’s formidable static and dynamic barriers, specifically the corneal epithelium, vitreous humor, and the inner limiting membrane. In this review, we present an anatomically guided framework for non-viral CRISPR/Cas9 delivery, mapping engineering strategies to specific ocular tissue targets. We first delineate the mechanisms of key physiological barriers, including the corneal stroma, aqueous humor circulation, and the vitreous–retina interface. Subsequently, we critically evaluate the latest advancements in non-viral platforms, such as pH-responsive lipid nanoparticles and engineered virus-like particles. The core focus of this review is on site-specific breakthrough strategies: from utilizing mucoadhesive polymers to counteract tear clearance in the cornea to exploiting specialized administration routes, such as suprachoroidal space and subretinal injection, to bypass retinal barriers, and deep-penetrating intravitreal carriers for targeting the photoreceptor-RPE complex. By integrating material science with precise administration routes, this review highlights feasible translational pathways for next-generation, carrier-free, or biomimetic ocular gene editing therapies. Full article