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Keywords = synthetic immunology

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24 pages, 4340 KB  
Review
cGAS/STING Signaling in Ulcerative Colitis: Mechanism and Therapeutic Opportunities
by Xinyi Dai, Jiaqi Zhang and Xudong Tang
Int. J. Mol. Sci. 2026, 27(14), 6513; https://doi.org/10.3390/ijms27146513 - 22 Jul 2026
Viewed by 417
Abstract
Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease characterized by mucosal inflammation and epithelial barrier disruption. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, the principal cytosolic DNA-sensing axis, has emerged as a critical node in UC pathogenesis. This [...] Read more.
Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease characterized by mucosal inflammation and epithelial barrier disruption. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, the principal cytosolic DNA-sensing axis, has emerged as a critical node in UC pathogenesis. This review elucidates the cGAS/STING signaling network in UC, from its upstream activation triggered by exogenous stimuli and leaked endogenous DNA to its downstream effects. We discuss how this pathway modulates distinct lines of intestinal defense, including the mechanical, chemical, and immunological barriers, while integrating its bidirectional crosstalk with the microbial barrier. Rather than exerting purely detrimental effects, cGAS/STING functions as a double-edged sword that coordinates both barrier homeostasis and inflammatory pathogenesis. Crucially, we summarize current pharmacological interventions, highlighting synthetic small molecules and bioactive natural products that target and modulate this axis to restore intestinal equilibrium. This framework provides a theoretical foundation for future precision therapies in UC. Full article
(This article belongs to the Section Molecular Immunology)
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25 pages, 2646 KB  
Review
Macrophage Membrane-Coated Nanoparticles for Immunomodulation and Bone Regeneration: Emerging Applications in Oral and Dental Implant Therapy
by Sara Derhambakhsh, Tulio Fernandez-Medina, Elsa Antunes, Suchandan Sikder, Ernest Jennings and Catherine M. Miller
Biomimetics 2026, 11(7), 482; https://doi.org/10.3390/biomimetics11070482 - 10 Jul 2026
Viewed by 425
Abstract
Macrophage membrane-coated nanoparticles (MMNPs) are an emerging class of biomimetic nanoplatforms that combine the immune-regulatory functions of macrophages with the structural versatility of synthetic nanoparticles (NPs). By retaining key membrane proteins and receptors, MMNPs exhibit natural targeting capabilities, immune interactions, and inflammatory site [...] Read more.
Macrophage membrane-coated nanoparticles (MMNPs) are an emerging class of biomimetic nanoplatforms that combine the immune-regulatory functions of macrophages with the structural versatility of synthetic nanoparticles (NPs). By retaining key membrane proteins and receptors, MMNPs exhibit natural targeting capabilities, immune interactions, and inflammatory site homing, making them promising tools for immunomodulation and targeted therapy. This review summarizes macrophage biology relevant to immune regulation and discusses how nanoparticle core properties, including size, surface charge, composition, and mechanical characteristics, influence membrane coating efficiency, stability, and biological performance. Current fabrication and characterization strategies for MMNPs are also discussed. Particular emphasis is placed on the therapeutic applications of MMNPs in inflammatory disorders, tissue regeneration, and oral and dental implant-related applications. Recent studies demonstrate that MMNPs can modulate macrophage polarization, sequester pro-inflammatory cytokines, remodel the immune microenvironment, and promote tissue repair and bone regeneration, highlighting their potential to improve implant integration and reduce inflammation-associated implant failure. Despite these promising advances, challenges remain regarding large-scale manufacturing, membrane preservation, reproducibility, and long-term biosafety. Continued interdisciplinary research in nanotechnology, immunology, and biomaterials engineering is expected to accelerate the clinical translation of MMNPs for regenerative and immunomodulatory therapies. Full article
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24 pages, 3738 KB  
Review
Poly(methyl vinyl ether-alt-maleic anhydride) and Its Derivatives: From Polymer Synthesis to Advanced Biomedical Applications
by Pedro Valentín Badía-Hernández, Rocío Díaz-Puertas, Paula del Carmen Sánchez-García, Alberto Falcó, Pilar García-Morales and Ricardo Mallavia
Polymers 2026, 18(13), 1667; https://doi.org/10.3390/polym18131667 - 6 Jul 2026
Viewed by 468
Abstract
Poly(methyl vinyl ether-alt-maleic anhydride) (PMVEMA) is a versatile synthetic copolymer that has gained considerable attention in biomedical and pharmaceutical applications due to its biocompatibility, biodegradability, bioadhesive properties and chemical reactivity. This review summarizes the current knowledge regarding the derivatives, physicochemical properties, [...] Read more.
Poly(methyl vinyl ether-alt-maleic anhydride) (PMVEMA) is a versatile synthetic copolymer that has gained considerable attention in biomedical and pharmaceutical applications due to its biocompatibility, biodegradability, bioadhesive properties and chemical reactivity. This review summarizes the current knowledge regarding the derivatives, physicochemical properties, functionalization and crosslinking strategies of PMVEMA, with particular emphasis on their relevance to biomedical applications. A comprehensive literature analysis was performed using major scientific databases, combined with artificial intelligence-assisted text mining, to identify the principal research trends associated with PMVEMA. The reviewed studies demonstrate that the reactive anhydride groups of PMVEMA enable the formation of a wide variety of derivatives, including hydrogels, nanoparticles and nanofibers with tunable properties. These characteristics have facilitated its application in different fields, including immunology, drug delivery, dentistry and dermatology. In particular, PMVEMA-based systems exhibit enhanced mucosal adhesion, controlled drug release, immunoadjuvant activity and biocompatibility in vitro and in vivo. Despite its broad applicability, further studies are still needed to fully elucidate its biodegradation mechanisms in vivo and optimize its clinical translation. Full article
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17 pages, 1191 KB  
Perspective
Perspective on Lessons Not Learned: From Coley’s Toxins to Microbial Drug Delivery, Guidance for Institutional Review Boards (IRBs)
by Brian P. Hanley, Alejandro J. Betancourt, Gustavo Gross and Wilbur (Bo) Bowne
Int. J. Mol. Sci. 2026, 27(13), 5985; https://doi.org/10.3390/ijms27135985 - 3 Jul 2026
Viewed by 477
Abstract
The bacterial and toxin methods of cancer treatment date back 130 years. This paradigm rests on nonspecific bacterial-toxin-generated immunotherapy. This high-risk oncology research is experiencing a renaissance of methods that are among the most effective yet. Glioblastomas and other resistant cancers are the [...] Read more.
The bacterial and toxin methods of cancer treatment date back 130 years. This paradigm rests on nonspecific bacterial-toxin-generated immunotherapy. This high-risk oncology research is experiencing a renaissance of methods that are among the most effective yet. Glioblastomas and other resistant cancers are the modern touchpoint, because of remission history following sepsis. Spurred by recent research deaths, we discuss protocols IRBs should consider in live bacterial or synthetic immuno-stimulatory trials. Human systemic inflammatory response syndrome immunology is unique due to non-functioning SIGLEC-13 and 17, which control excessive Toll-like receptor 4 (TLR-4) signaling. This is not a technicality like human CD8+/CD4+ T cells. SIGLEC-13&17 consequences are profound; humans are ≈330–200,000 times more sensitive to LPS/endotoxin than mice and rats. This human TLR-4 difference also applies to gene therapy and should inform the results from any animal model, including non-human primates. Clinical TLR-4 stimulation takes two forms: bacterial infection and sterile TLR-4 stimulators, and treatments differ. The stereotactic injection of calculated amounts of adjuvants like endotoxin, venoms/components, or synthetic alternatives may be safer than live bacteria. Inadequate planning for risk elements, basic predictive models, and treatments will likely cause death. Full article
(This article belongs to the Section Molecular Immunology)
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13 pages, 857 KB  
Article
Detection of Latent Tuberculosis Infection in Patients with Rheumatological Diseases Who Receive Immunosuppressive Therapy
by Anna Starshinova, Adilia Sabirova, Alexey Maslyanskiy, Irina Grigorieva, Raul Sharipov, Ravil Tukfatullin, Aleksandr Panteleev, Michail Nazarenko and Dmitry Kudlay
Diagnostics 2026, 16(12), 1883; https://doi.org/10.3390/diagnostics16121883 - 17 Jun 2026
Viewed by 315
Abstract
Background/Objectives: Latent tuberculosis infection (LTBI) is a persistent immune response to Mycobacterium tuberculosis antigens in the absence of clinically active tuberculosis. It is now established that progression from LTBI to active tuberculosis is directly associated with immune dysregulation, which frequently occurs [...] Read more.
Background/Objectives: Latent tuberculosis infection (LTBI) is a persistent immune response to Mycobacterium tuberculosis antigens in the absence of clinically active tuberculosis. It is now established that progression from LTBI to active tuberculosis is directly associated with immune dysregulation, which frequently occurs in immune-mediated diseases requiring treatment with immunosuppressive agents. The aim of this study was to identify LTBI in patients with rheumatological diseases receiving immunosuppressive therapy using contemporary immunodiagnostic methods. Materials and Methods: A retrospective, prospective, group-control study was conducted, analyzing the results of immunodiagnostics in patients with rheumatological diseases on immunosuppressive therapy and without established contact with tuberculosis patients (n = 44; main group). The control group consisted of healthy individuals (n = 51) with no history of tuberculosis contact, clinical or radiological manifestations of the disease, or signs of chronic pathology exacerbation. Both groups were predominantly female (72.7% in the main group and 62.8% in the control group). The mean age in the patient group was 49.1 years (95% CI [44.77; 53.43]). Rheumatoid arthritis was diagnosed in 29.6% (13) of patients (95% CI [16.06; 43.03]). Articular syndrome was observed in at least 72.7% (32) of patients (95% CI [59.57; 85.89]). In 54.6% (24) of cases (95% CI [39.83; 69.26]), patients received biologic immunosuppressive therapy as basic treatment. In 15.9% (7) of cases (95% CI [5.10; 26.72]), patients received conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Of these, 71.43% (5) (95% CI [35.24; 92.44]) underwent comprehensive examination to exclude active tuberculosis prior to biologic therapy initiation. For immunodiagnostics, all subjects underwent an interferon-gamma release assay (IGRA) and/or testing with a recombinant tuberculosis antigen (ATR) sample, with dynamic assessment of test results. All patients with positive immunodiagnostic results underwent multidetector computed tomography of the chest organs. The level of LTBI in the comparison groups was defined as the percentage of positive immunological test results at a significance level of p < 0.05. Statistical data processing was performed using Microsoft Excel 2019. Results: In the main group, positive immunodiagnostic results were recorded in 20.5% (9) of cases (95% CI [8.54; 32.37]), which is significantly higher than in the control group of healthy individuals (5.8% (3), 95% CI [1.41; 16.54]). This reflects statistically significant differences in immunological test results between groups receiving and not receiving immunosuppressive therapy (χ2 = 4.545, p = 0.034). Dynamic evaluation of the ATR sample revealed positive results in 21.7% (5) of cases (95% CI [4.88; 38.60]), with four out of five patients demonstrating positive conversion. In the third assessment, positivity was observed in 33.33% (5) of cases (95% CI [9.48; 57.19]), which was higher than in the first (χ2 = 1.025, p = 0.312) and second assessments (χ2 = 0.629, p = 0.428), although these differences were not statistically significant. Notably, in two out of five patients, the ATR test result changed from negative to positive. Conclusions: In patients with rheumatological diseases receiving immunosuppressive therapy, LTBI was detected in 20.5%, which is significantly higher than in healthy individuals (5.8%, p = 0.034). Furthermore, there was an increase in the proportion of positive tests over time (up to 21.7% and 33.3% on immunotherapy), suggesting an increasing risk of progression to active tuberculosis infection. Full article
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17 pages, 9234 KB  
Review
Codon-Pair Deoptimized (CPD) Intranasal RSV Vaccines: A Novel Strategy for Infant Protection
by Wael Alturaiki
Int. J. Mol. Sci. 2026, 27(12), 5231; https://doi.org/10.3390/ijms27125231 - 9 Jun 2026
Viewed by 334
Abstract
Respiratory syncytial virus (RSV) is considered the leading causative agent of acute lower respiratory infections in infants and young children worldwide, which makes it a major contributor to pediatric morbidity and mortality. Infants are especially susceptible to severe disease in early life, which [...] Read more.
Respiratory syncytial virus (RSV) is considered the leading causative agent of acute lower respiratory infections in infants and young children worldwide, which makes it a major contributor to pediatric morbidity and mortality. Infants are especially susceptible to severe disease in early life, which underlines the urgent need for developing effective immunization strategies against this virus. However, the development of vaccines against RSV has long been associated with significant challenges. For example, initial attempts, especially those involving formalin-inactivated RSV, resulted in vaccine-enhanced respiratory disease upon subsequent infection, which set a significant safety obstacle for future vaccine candidates. Other challenges facing vaccine development against RSV include the short-lived immunity induced by natural infection, lack of clear correlates of immunity, and immune naivety in infants. Recent breakthroughs in structural virology and immunology have provided insights into protective immunity against RSV, especially regarding neutralizing antibodies that recognize the virus in its prefusion conformation of the viral F protein. Among promising vaccine candidates, intranasal live-attenuated vaccines have emerged as especially promising for infant immunization, especially considering their close mimicry of natural infection that can elicit systemic as well as mucosal immunity in the respiratory tract. A newly emerging approach for live-attenuated virus vaccine development is codon-pair deoptimization (CPD), which is based on synthetic recoding that reduces viral replicative capacity while maintaining intact protein sequences and structure. The preclinical results of CPD-based RSV candidates have provided evidence of such vaccines’ ability to elicit robust immunity while maintaining favorable safety profiles. This review addresses the major challenges associated with the development of effective RSV vaccines for infant immunization, with particular emphasis on lessons learned from previous vaccine failures and recent advances in RSV vaccine development, particularly CPD-based attenuation strategies. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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17 pages, 6934 KB  
Article
Identification of Conserved Cross-Reactive B-Cell Epitopes in CPV1 and CPV2 L1 Proteins with Vaccine Potential
by Yuge Wang, Yingyi Chen, Kaixin Wang, Youqing Yuan, Haojie Sun, Youming Yuan, Jixian Wang, Zhicai Yang, Yi Yang, Naidong Wang, Deyong Duan and Aibing Wang
Vaccines 2026, 14(6), 512; https://doi.org/10.3390/vaccines14060512 - 6 Jun 2026
Viewed by 414
Abstract
Background/Objectives: Canine papillomavirus (CPV) is an important viral pathogen associated with papillomatosis in dogs, with canine papillomavirus type 1 (CPV1) and type 2 (CPV2) among the most prevalent and clinically relevant genotypes. The L1 capsid protein is a major immunogenic antigen of papillomaviruses; [...] Read more.
Background/Objectives: Canine papillomavirus (CPV) is an important viral pathogen associated with papillomatosis in dogs, with canine papillomavirus type 1 (CPV1) and type 2 (CPV2) among the most prevalent and clinically relevant genotypes. The L1 capsid protein is a major immunogenic antigen of papillomaviruses; however, conserved linear B-cell epitopes shared between CPV genotypes remain poorly defined. This study aimed to identify conserved cross-reactive B-cell epitopes within CPV1 and CPV2 L1 proteins and to evaluate their preliminary immunoreactivity. Methods: Conserved linear B-cell epitopes were predicted through integrated bioinformatic and structural analyses based on sequence conservation and surface accessibility. Three candidate epitopes were selected. Recombinant CPV1 and CPV2 L1 proteins were expressed in Escherichia coli (E. coli), purified, used as recombinant L1 antigens, together with BSA-conjugated synthetic epitope peptides for mouse immunization. Antigen-specific IgG responses were assessed by ELISA, antigen-associated IFN-γ responses were evaluated by ELISpot, and cross-reactive antibody recognition was assessed by Western blot. Results: Recombinant L1 proteins induced strong antigen-specific IgG responses in mice. The selected peptides induced detectable but weaker humoral responses compared with the recombinant L1 proteins. Among the three epitopes, TPSGSLV and TVVDNTR elicited antibodies that recognized both CPV1 and CPV2 L1 proteins, while the epitope VIVPKVS showed minimal or no detectable immunoreactivity. ELISpot analysis showed only modest antigen-associated IFN-γ responses, particularly in peptide-immunized groups. Conclusions: This study identified conserved cross-reactive linear B-cell epitope candidates within CPV1 and CPV2 L1 proteins and provided preliminary immunological evidence supporting their potential relevance for CPV antigen design. However, peptide-induced responses were weaker than those induced by recombinant L1 proteins, and VLP formation, antibody neutralizing activity, and protective efficacy were not evaluated. Further studies in dogs, including optimized antigen-display platforms, neutralization assays, and protection studies, are required to determine the practical value of these epitopes for CPV vaccine development. Full article
(This article belongs to the Special Issue Animal Vaccines: 2nd Edition)
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27 pages, 2765 KB  
Review
In Vivo mRNA-Lipid Nanoparticle CAR-T Cell Engineering: Advances, Challenges, and Clinical Translation
by Vipin K. Yadav, Priyanka Yadav, Sreevidya Mallappa and Praveen Neeli
Biomedicines 2026, 14(6), 1276; https://doi.org/10.3390/biomedicines14061276 - 3 Jun 2026
Cited by 1 | Viewed by 2543
Abstract
Chimeric antigen receptor T (CAR-T) cell therapy has transformed the treatment of hematologic malignancies, yet its broader application, particularly in solid tumors, remains constrained by high cost, labor-intensive manufacturing, limited production capacity, and variable clinical performance, as well as barriers such as poor [...] Read more.
Chimeric antigen receptor T (CAR-T) cell therapy has transformed the treatment of hematologic malignancies, yet its broader application, particularly in solid tumors, remains constrained by high cost, labor-intensive manufacturing, limited production capacity, and variable clinical performance, as well as barriers such as poor trafficking, antigen heterogeneity, and an immunosuppressive tumor microenvironment. In vivo CAR-T cell engineering, in which CAR-T cells are generated directly within the patient, offers a paradigm shift by eliminating the need for ex vivo cell processing and complex logistical infrastructure. Among emerging approaches, messenger RNA (mRNA)-loaded lipid nanoparticles (LNPs) have emerged as a promising and clinically tractable platform for in vivo CAR-T cell generation, enabling direct reprogramming of T lymphocytes within the patient and thereby circumventing the need for leukapheresis, viral vector production, and prolonged ex vivo culture, effectively transforming the patient into their own cell therapy factory. This review synthesizes advances in mRNA-LNP-mediated in vivo CAR-T cell generation, encompassing ionizable lipid chemistry and emerging T cell-targeted delivery strategies, including surface functionalization approaches. We discuss the implications of transient CAR expression for immune activation, safety, and therapeutic durability, alongside CAR design optimization through co-stimulatory domains and safety switches. Preclinical evidence from murine tumor models and non-human primates is integrated with current regulatory considerations, and key barriers to clinical translation are highlighted. Collectively, progress in nucleic acid delivery, synthetic immunology, and precision medicine positions in vivo mRNA-CAR-T therapy as a promising modality for oncology and beyond. Full article
(This article belongs to the Special Issue mRNA Personalized Cancer Vaccines and Immune-Oncology)
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29 pages, 10928 KB  
Review
A Narrative Review on Preclinical Small Molecules for Bone Regeneration: Mechanisms, Delivery Strategies, and Translational Gaps
by Abdurahman A. Niazy
Future Pharmacol. 2026, 6(2), 23; https://doi.org/10.3390/futurepharmacol6020023 - 10 Apr 2026
Viewed by 862
Abstract
Treatment for large critical-sized bone defects and impaired fracture healing remain challenging. Clinically used protein-based osteoinductive factors, such as recombinant bone morphogenetic proteins (BMPs), can be effective; however, they are costly and limited by stability, dose-delivery issues, and safety concerns. Preclinical small molecules [...] Read more.
Treatment for large critical-sized bone defects and impaired fracture healing remain challenging. Clinically used protein-based osteoinductive factors, such as recombinant bone morphogenetic proteins (BMPs), can be effective; however, they are costly and limited by stability, dose-delivery issues, and safety concerns. Preclinical small molecules offer an alternative because they are chemically stable, scalable to manufacture, and readily integrated for systemic administration or localized release from scaffolds, hydrogels, cements, and implant coatings. With an emphasis on delivery formats and mechanistic themes, this review examines small molecules that have been shown to improve bone regeneration in preclinical models, contrasting those of biological origin with synthetic and repurposed compounds. Across studies, these selected compounds promote osteoblast commitment, differentiation, and matrix mineralization via BMP/Smad signaling and Wnt/beta-catenin (β-catenin) activation, often through glycogen synthase kinase-3 beta (GSK-3β) inhibition or relief of pathway antagonism or Hedgehog (Hh) pathway stimulation. Beyond osteoinduction, several candidates address issues that commonly limit repair, including angiogenesis, oxidative stress, inflammatory tone, osteoimmune regulation, and suppression of osteoclast-mediated resorption. Direct head-to-head comparisons are rare across both classes and reporting heterogeneity complicates interpretation. Key translational gaps include limited cytotoxicity and immunologic profiling, dose and release optimization, durability of benefit, and insufficient evaluation of rational combinations. More rigorous in vivo studies, including larger animal models and standardized outcome metrics, are needed to prioritize promising candidates and guide clinical development. Full article
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47 pages, 742 KB  
Review
Plant-Derived Nanocarriers for Drug Delivery: A Unified Framework Integrating Extracellular Vesicles, Engineered Phytocarriers, Hybrid Platforms, and Bioinspired Systems
by Adina-Elena Segneanu, George Dan Mogoşanu, Cornelia Bejenaru, Roxana Kostici and Ludovic Everard Bejenaru
Plants 2026, 15(6), 908; https://doi.org/10.3390/plants15060908 - 15 Mar 2026
Cited by 1 | Viewed by 1982
Abstract
Plant-derived extracellular vesicles (PDEVs), engineered phytosomes, bioinspired polymeric plant-based nanoparticles (PBNPs), hybrid phyto-inorganic nanocomposites, green-synthesized metal nanoparticles, self-assembled nanoarchitectures, and multifunctional composites represent a rapidly advancing class of sustainable, nature-inspired nanocarriers. These platforms combine exceptional biocompatibility, negligible immunogenicity, and renewable sourcing with tunable [...] Read more.
Plant-derived extracellular vesicles (PDEVs), engineered phytosomes, bioinspired polymeric plant-based nanoparticles (PBNPs), hybrid phyto-inorganic nanocomposites, green-synthesized metal nanoparticles, self-assembled nanoarchitectures, and multifunctional composites represent a rapidly advancing class of sustainable, nature-inspired nanocarriers. These platforms combine exceptional biocompatibility, negligible immunogenicity, and renewable sourcing with tunable drug loading, targeted delivery, and controlled release properties. This review synthesizes translational advances from 2020 to 2026, covering scalable isolation/bioprocessing (bioreactors, elicitation), multi-parametric physicochemical/multi-omics characterization, rational engineering/hybridization, and rigorous in vitro/in vivo assessments of uptake, biodistribution, pharmacokinetic (PK), and efficacy. Phytosomes and PBNPs markedly enhance oral bioavailability and targeted delivery of lipophilic phytochemicals, while PDEVs offer unique immunomodulatory, anti-inflammatory, and gene-regulatory activities. Hybrid and green-synthesized systems provide structural stability, redox modulation, and synergistic effects, and self-assembled/multifunctional composites address solubilization barriers with stimuli-responsive design. Early-phase human studies on grapefruit-, ginger-, turmeric-, and ginseng-derived PDEVs report excellent short-term safety, favorable PK, and preliminary bioactivity signals, with no observed immunogenicity or dose-limiting toxicities; however, these trials remain exploratory, constrained by small sample sizes and safety-focused endpoints. Despite challenges, including methodological heterogeneity, variable yields, long-term safety uncertainties (notably for inorganic hybrids), and regulatory ambiguities, emerging strategies such as clustered regularly interspaced short palindromic repeats (CRISPR)-engineered plant line; artificial-intelligence-driven process optimization; standardized guidelines, and integrated clinical, intellectual property, and commercialization frameworks are progressively addressing these barriers. Collectively, these advances position plant-derived nanocarriers as immunologically privileged, eco-friendly alternatives to synthetic and mammalian platforms, laying the foundation for a sustainable era of precision phytomedicine. Full article
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21 pages, 2326 KB  
Article
Immunogenicity and Protective Effects of an Ag85B Tuberculosis Subunit Vaccine Formulated with Synthetic TLR4 Agonists in BCG-Boosted Mice
by Soo-Min Kim, Jin-Seung Yun, EunJung Shin, Jinhee Lee, You-Jin Kim, Hye-Sook Jeong, Yong Woo Jung and Dokeun Kim
Vaccines 2026, 14(3), 214; https://doi.org/10.3390/vaccines14030214 - 26 Feb 2026
Viewed by 1330
Abstract
Background/Objectives: Tuberculosis (TB) remains a major global health challenge, and the Bacillus Calmette–Guérin (BCG) vaccine has limited efficacy against adult pulmonary disease. Protein subunit vaccines are a promising alternative but require strong adjuvants to induce cell-mediated immunity. Synthetic agonists targeting toll-like receptor 4 [...] Read more.
Background/Objectives: Tuberculosis (TB) remains a major global health challenge, and the Bacillus Calmette–Guérin (BCG) vaccine has limited efficacy against adult pulmonary disease. Protein subunit vaccines are a promising alternative but require strong adjuvants to induce cell-mediated immunity. Synthetic agonists targeting toll-like receptor 4 (TLR4) and stimulators of interferon genes (STINGs) have emerged as effective immunostimulants. Therefore, we aimed to evaluate the immunogenicity and protective efficacy of Ag85B-based subunit vaccines formulated with synthetic TLR4 and STING agonists in a BCG-boosted mouse model. Methods: Three synthetic adjuvants—QTP709-1, QTP709-3, and QTP701—were formulated as oil-in-water emulsions containing distinct surfactant and immunostimulant components. The potential of vaccine formulations to activate dendritic cells (DCs) and elicit Ag85B-specific immune responses, including IgG subclass levels, interferon-γ (IFN-γ) enzyme-linked immunosorbent spots, and polyfunctional T-cell responses, was assessed by flow cytometry. Protective efficacy was evaluated based on pulmonary bacterial burden and histopathology following Mycobacterium tuberculosis (M. tb) Erdman challenge. Results: All formulations promoted DC maturation and enhanced antigen-specific immune responses. Each adjuvant elicited strong Ag85B-specific humoral immunity, increased IFN-γ secretion, and polyfunctional CD4+ and CD8+ T cells co-producing IFN-γ, TNF-α, and interleukin-2. Among them, QTP709-1 was associated with increased levels of chemokine receptor 5-associated chemokines and showed a trend toward reduced lung bacterial burden and histopathological inflammation following M. tb challenge. Conclusions: Synthetic TLR4 and STING agonists were associated with enhanced immunogenicity of TB subunit vaccines and showed evidence of protective potential, with TLR4-based formulations exhibiting more pronounced immunological responses. QTP709-1 exhibited strong immunostimulatory and protective effects, supporting its potential as a candidate adjuvant for next-generation TB vaccines. Full article
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13 pages, 855 KB  
Article
Evaluation of Antibodies Induced by Melanoma Helper Peptide Vaccine and Their Modulation by Vaccine Adjuvants
by Emily G. Ashkani, Anna M. Dickinson, Walter C. Olson, Justin J. Taylor and Craig L. Slingluff
Vaccines 2026, 14(2), 195; https://doi.org/10.3390/vaccines14020195 - 21 Feb 2026
Viewed by 1022
Abstract
Background/Objectives: Vaccines targeting melanoma antigens can elicit CD8+ T cell responses, but a growing body of work suggests CD4+ T cells also play a role in tumor control. Induction of CD4+ cells may also support B cells in producing tumor [...] Read more.
Background/Objectives: Vaccines targeting melanoma antigens can elicit CD8+ T cell responses, but a growing body of work suggests CD4+ T cells also play a role in tumor control. Induction of CD4+ cells may also support B cells in producing tumor antigen-specific antibodies (Abs). We investigated Abs induced by vaccination with a cocktail of six class II MHC-restricted melanoma peptides (6MHP) and the effect of adjuvant type on Ab isotypes. We hypothesized that the vaccines would induce Abs that respond to different epitopes on individual peptides and that IgG isotype distribution varies with different vaccine adjuvants. Methods: Sera from patients who received a 6MHP vaccine were evaluated with enzyme-linked immunosorbent assays to map epitopes for polyclonal Ab responses to synthetic melanoma peptides. IgG isotypes of Ab responses to 6MHP were assessed in patients who received one of four adjuvants (Incomplete Freund’s Adjuvant (IFA) alone, IFA + polyICLC, IFA + systemic metronomic cyclophosphamide (mCy), or IFA + polyICLC + systemic mCy) to characterize IgG isotype distribution. Results: Epitope mapping revealed that at least 50% of patients had responses to two or more epitopes on the same peptide, suggesting polyclonal Ab responses. Serum evaluation for IgG isotypes showed predominant induction of IgG1 and IgG3. Mean total IgG was highest when IFA and polyICLC were used in combination. Patients who received TLR3 agonist polyICLC had significantly higher concentrations of total IgG, IgG1, and IgG3 compared to patients who did not receive polyICLC. Conclusions: Vaccine-induced Abs may respond to multiple epitopes within the same peptide, warranting further studies into their ability to facilitate antigen uptake and presentation through the formation of large immune complexes. The findings also show that adding polyICLC to IFA can significantly enhance Ab responses. Collectively, this work underscores the immunologic potential of peptide-induced Abs and the importance of adjuvant selection in cancer vaccine design. Full article
(This article belongs to the Section Vaccination Against Cancer and Chronic Diseases)
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20 pages, 2634 KB  
Article
Vaccination with an African Swine Fever Virus Multiepitope Protein Chitosan Nanoparticle-Based Subunit Vaccine Elicits Robust Immune Responses In Vivo
by Carolyn M. Lee, Raksha Suresh, Patricia A. Boley, Olaitan Comfort Shekoni, Jennifer Schrock, Sara Dolatyabi, Mithilesh Singh, Saroj Khatiwada, Kush Kumar Yadav, Dina Bugybayeva, Juliette Hanson, Renukaradhya J. Gourapura and Scott P. Kenney
Vaccines 2026, 14(2), 187; https://doi.org/10.3390/vaccines14020187 - 17 Feb 2026
Cited by 1 | Viewed by 2628
Abstract
Background/Objectives: African swine fever virus (ASFV), the causative agent of African swine fever (ASF), is a highly contagious virus affecting both domestic and feral pig populations with mortality rates approaching 100% within one week of infection. Currently, there are limited treatments or vaccines [...] Read more.
Background/Objectives: African swine fever virus (ASFV), the causative agent of African swine fever (ASF), is a highly contagious virus affecting both domestic and feral pig populations with mortality rates approaching 100% within one week of infection. Currently, there are limited treatments or vaccines available to control the disease. Although ASF is endemic in sub-Saharan Africa, the virus has also spread widely, reaching regions of the European Union, Russia, China, Southeast Asia, and, more recently, to the Dominican Republic and Haiti, bringing the threat closer to the United States (U.S.). ASF introduction to the U.S. would have severe consequences for swine producers and the national pork industry. Consequently, there is an urgent need to develop effective vaccine strategies to manage ongoing outbreaks abroad and mitigate the risk of future ASF incursions. Recent efforts have identified several ASFV epitopes and evaluated them in experimental vaccine trials. However, these vaccine candidates have elicited limited protective immune responses and have not demonstrated full protective efficacy. Methods: In this study, we employed in silico modeling and epitope prediction tools to design a synthetic multiepitope ASF protein incorporating key immunogenic regions of ASFV. The goal was to generate a single-antigen construct capable of inducing broad and robust immune responses when formulated with an established nanoparticle-based vaccine platform. The multiepitope ASF protein was subsequently expressed and entrapped into mannose-conjugated chitosan (M-CS) nanoparticles for vaccine formulation. The candidate vaccine, formulated with M-CS nanoparticle-entrapped adjuvant (ADU S100), was administered intramuscularly to pigs, and both T- and B-cell responses were assessed following the primary (DPV 22) and booster (DPV 42) doses. Results: Our M-CS ASF protein vaccine elicited antigen-specific T- and B-cell responses, both of which are recognized as central correlates of protection against ASFV. Conclusions: These promising preliminary immunological findings suggest that this nanoparticle vaccine has the potential to confer protection against ASFV challenge, a hypothesis that will be examined in future studies. Full article
(This article belongs to the Special Issue African Swine Fever Virus Immunotherapies and Vaccine Development)
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22 pages, 2039 KB  
Review
Phage-Based Approaches to Chronic Pseudomonas aeruginosa Lung Infection in Cystic Fibrosis
by Wontae Hwang, Ji Hyun Yong, Bryan R. Lenneman and Lael M. Yonker
Antibiotics 2026, 15(2), 125; https://doi.org/10.3390/antibiotics15020125 - 27 Jan 2026
Cited by 1 | Viewed by 2228
Abstract
Chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) represent one of the most treatment-refractory bacterial diseases, sustained by biofilm formation, metabolic dormancy, and adaptive antibiotic resistance evolution. While bacteriophage (phage) therapy has emerged as a promising alternative for multidrug-resistant (MDR) pathogens, clinical [...] Read more.
Chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) represent one of the most treatment-refractory bacterial diseases, sustained by biofilm formation, metabolic dormancy, and adaptive antibiotic resistance evolution. While bacteriophage (phage) therapy has emerged as a promising alternative for multidrug-resistant (MDR) pathogens, clinical studies in CF have demonstrated transient reductions in bacterial burden without achieving complete eradication. This review integrates molecular, evolutionary, and immunological findings to explain the multifactorial barriers that limit phage therapeutic efficacy in chronic CF infections. We highlight three major obstacles: (i) bacterial dormancy and persistence within biofilms that restrict phage adsorption and replication; (ii) hypermutability and extensive genotypic diversification of CF-adapted P. aeruginosa, which accelerate phage resistance evolution and necessitate broad host-range coverage; and (iii) CF-specific immune constraints—including a dysfunctional innate immune system and phage-neutralizing humoral immunity—that reduce phage bioavailability and undermine sustained bacterial clearance. Emerging strategies to overcome these challenges include the discovery of dormant-targeting phages capable of replicating in metabolically quiescent cells, evolution-informed phage training to delay resistance evolution, and synthetic phage engineering approaches designed to disrupt biofilms and expand host-range coverage. In parallel, computational or artificial intelligence (AI)-guided frameworks for phage cocktail design and cystic fibrosis transmembrane conductance regulator (CFTR) modulator-mediated restoration of host immune function together offer a more integrated therapeutic paradigm that unites phage biology and host immune context. By unifying clinical outcomes with mechanistic, evolutionary, and immunological perspectives, this review outlines a next-generation framework for phage therapy in CF aimed at achieving more durable therapeutic outcomes. Full article
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Review
Insights into Non-Antibiotic Alternative and Emerging Control Strategies for Chicken Coccidiosis
by Rochelle A. Flores, Paula Leona C. Fletcher, Kyu-Yeol Son and Wongi Min
Animals 2026, 16(2), 348; https://doi.org/10.3390/ani16020348 - 22 Jan 2026
Cited by 6 | Viewed by 2351
Abstract
Coccidiosis, caused by an obligate intracellular parasite of the genus Eimeria, is the most economically parasitic disease in poultry. Long-term reliance on synthetic anticoccidials and ionophores has accelerated the emergence of drug resistance and intensified the need for effective, residue-free alternatives. This [...] Read more.
Coccidiosis, caused by an obligate intracellular parasite of the genus Eimeria, is the most economically parasitic disease in poultry. Long-term reliance on synthetic anticoccidials and ionophores has accelerated the emergence of drug resistance and intensified the need for effective, residue-free alternatives. This narrative review synthesizes findings from peer-reviewed studies published between 1998 and 2025, summarizing advances in non-antibiotic control strategies encompassing five domains: (i) phytochemicals and botanicals, (ii) functional nutrition and mineral modulators, (iii) microbial and gut modulators, (iv) host-directed immunological and biotechnological approaches, and (v) precision and omics-guided biotherapeutic platforms. These approaches consistently reduce lesion severity, oocyst shedding, oxidative stress, and mortality while improving growth parameters in a variety of Eimeria models. However, translation to field settings remains constrained by variable bioactive composition, limited standardization, inadequate pharmacokinetic data, and the scarcity of large-scale, multi-farm validation studies. This review provides a concise summary of current evidence and delineates critical knowledge gaps to guide the development, optimization, and deployment of next-generation anticoccidial strategies. Together, natural products and emerging biotechnologies provide a promising foundation for sustainable, high-welfare, antibiotic-independent coccidiosis control. Full article
(This article belongs to the Section Poultry)
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