Search Results (1,660)

Background: Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in infants, seniors, and immunocompromised individuals, contributing substantially to the global disease burden. Given the limited preventive options available, developing an effective and safe vaccine remains a public health priority. Methods: An mRNA vaccine encoding the RSV PreF protein was designed and prepared. Antigen properties were evaluated in silico, and the coding sequence was optimized using NLP algorithms. The stability and translational efficiency of the mRNA constructs were verified through in vitro and in vivo assays, followed by immunogenicity evaluation of the formulated mRNA vaccines in a BALB/c mouse model. Results: The optimized mRNA showed predicted improvements in structural stability and a lower free energy state, which were associated with increased translational efficacy in vitro. Correct antigen conformation and retention of key epitopes were confirmed by intracellular staining followed by flow cytometry. A balanced Th1-biased immune response was induced in mice, characterized by high levels of neutralizing antibodies and antigen-specific T-cell immunity, along with enhanced memory T-cell proliferation and differentiation, indicating long-term immunological memory. Conclusions: A novel RSV PreF mRNA vaccine was successfully developed via optimization of protein structure and mRNA sequence. Superior immunogenicity was demonstrated in the BALB/c mouse model, together with promising potential in terms of vaccine safety and immunological persistence. These findings represent a promising step forward in the pursuit of an effective RSV vaccine and suggest the potential of the developed mRNA vaccine to induce substantial immune responses that may correlate with protection in future challenge studies. Full article

Background/Objectives: Our previous study demonstrated that while the third SARS-CoV-2 booster effectively enhanced immunity against the Delta subvariant, its protection declined over time. This study aimed to evaluate and compare the humoral and cellular immune responses, as well as reactogenicity, of the mRNA-1273 vaccine administered as a fourth booster in healthy Thai adults previously vaccinated with two doses of CoronaVac (CV) followed by a third dose of either AZD1222 (AZ) or BNT162b2 (BNT). Methods: Participants received a single 100 µg (0.5 mL) intramuscular dose of mRNA-1273. Blood samples were collected at baseline (D0), D14, D90, and D180 to assess anti-RBD IgG, conduct a surrogate virus neutralization test (sVNT) against the Delta and Omicron variants, and assess IFN-γ levels and reactogenicity. Results: Both 2CV/AZ- and 2CV/BNT-primed groups exhibited comparable local and systemic reactogenicity. The fourth mRNA-1273 dose markedly increased Delta variant inhibition within 14 days in both groups and remained at high levels at Days 90 and 180. sVNT inhibition against Omicron rose similarly in both groups at Day 14; it declined sharply by Days 90 and 180, with the 2CV/AZ-primed group showing significantly lower levels than the 2CV/BNT-primed group. Baseline anti-RBD IgG levels were lower in the 2CV/AZ group (p = 0.003) but surpassed those of the 2CV/BNT group by Day 14, with no significant differences at later time points. IFN-γ responses followed a similar pattern to anti-RBD IgG Conclusions: A heterologous fourth mRNA-1273 booster in both 2CV/AZ- and 2CV/BNT-primed groups effectively enhances B-cell and T-cell responses against SARS-CoV-2. However, emerging variants such as Omicron may still pose challenges. The trial was registered with the Thai Clinical Trials Registry: the name of the registry: “The comparison of immune response to the 4th dose booster with mRNA-1273 COVID-19 vaccine in individuals who had received 2 doses of CoronaVac and booster with ChAdOx-1 or BNT162b2 COVID-19 vaccine”, TCTR20220205002 on 5 February 2022. Full article

(1) Objective. To conduct a comparative bioinformatics analysis of the transcriptomic profiles of peri-implantitis and periodontitis to identify common and specific molecular signatures underlying their pathogenesis, as well as molecular parallels with atherosclerosis. (2) Methods: We used datasets from the Gene Expression Omnibus (GEO) database: dataset GSE223924 (30 gingival tissue samples from patients with peri-implantitis, periodontitis, and healthy subjects) and GSE100927 (atherosclerotic and control tissue; n = 104). Differentially expressed genes (DEGs) were identified based on the criteria: |logFC| > 1 and FDR < 0.05. To quantitatively assess the relative abundance of immune cells, we used the xCell deconvolution algorithm. (3) Results: In the peri-implantitis group, 3669 DEGs with upregulated expression and 3106 with downregulated expression were identified; in the periodontitis group, 1968 and 1250 DEGs, respectively. Functional analysis of the upregulated DEGs revealed activation of inflammatory processes, cell adhesion, and angiogenesis in both diseases. Key differences lay in the activation of adaptive immune mechanisms in peri-implantitis (enrichment of the “graft rejection” and “T-cell receptor signaling”) and innate immunity in periodontitis (enrichment of the “lipopolysaccharide response” and “Toll-like receptors (TLR) signaling” pathways). Analysis of downregulated DEGs revealed more profound disruptions in cytoskeletal organization and epithelial differentiation in periodontitis, as well as suppression of xenobiotic and lipid metabolism in both diseases. xCell deconvolution confirmed a significant increase in B cells, neutrophils, monocytes, M1 macrophages, and dendritic cells in peri-implantitis, and also revealed a trend toward an increase in these cells in periodontitis (p > 0.05), which is consistent with the activation of TLR signaling. In periodontitis, a significant increase in M2 macrophages and a decrease in Th1 cells were observed. Comparison with atherosclerosis revealed 272 common DEGs with peri-implantitis and 173 common DEGs with periodontitis. Functional analysis of the common genes confirmed their role in leukocyte transendothelial migration, cytokine production, and the “Lipids and Atherosclerosis” pathway. (4) Conclusions: Functional analysis and immune deconvolution consistently demonstrate that peri-implantitis is characterized by statistically significant activation of both adaptive and innate immunity, whereas in periodontitis, the activation of innate immunity manifests primarily at the level of signaling pathways. The significant overlap found between the transcriptional profiles of both diseases and atherosclerosis may indicate the presence of common pathogenetic links. Full article

Background: The steady increase in allergic diseases among children has coincided with increased global vaccination coverage and the expansion of routine childhood immunization programs. This has contributed to the widespread belief that there is a possible link between immunoprophylaxis and allergic diseases. However, a number of scientific studies have demonstrated the protective effect of early neonatal immunization on the development of nonspecific immunological protection against infections. This is believed to be due to a shift in the immune response from the Th2 type, traditionally predominant in newborns, to the Th1 type, which reduces the risk of developing allergic diseases. Methods: This prospective cohort study analyzed the medical records of 2279 children born between 2018 and 2022 to evaluate the impact of neonatal BCG-M and hepatitis B (HepB) vaccination on the incidence of atopic dermatitis (AD) by 36 months of age. Factors analyzed included family history of allergy, cesarean section, prematurity, delayed initiation of breastfeeding, maternal antibiotic use during pregnancy, and antibiotic use in the child during the first three years of life. Results: The cumulative incidence of AD by 36 months of age was 19.9%. Timely neonatal vaccination coverage was 76.2% for BCG-M and 69.2% for HepB; by 12 months of age, these rates increased to 90.2% and 88.5%, respectively. A full-term birth demonstrated a significant protective effect (OR 0.52; 95% CI 0.30–0.93). A positive family history of allergy was the strongest predictor of AD (OR 21.49; 95% CI 14.4–32.9). Cesarean section was also significantly associated with AD (OR 1.30; 95% CI 1.01–1.65). AD incidence was comparable between vaccinated (20.5%) and non-vaccinated (17.5%) children (chi-squared with Yates’ correction, p = 0.192), indicating no statistically significant overall impact of immunization on AD risk. Conclusions: The development of AD is primarily driven by hereditary predisposition and specific perinatal factors rather than by routine immunization. These findings confirm that neonatal BCG-M and HepB vaccination does not increase the risk of AD, providing a scientific basis to address vaccine hesitancy. Full article

Lyme disease (LD) is classically defined as a tick-borne infection caused by Borrelia burgdorferi sensu lato (Bbsl). However, accumulating evidence indicates that, beyond microbial persistence, Bbsl infection can initiate sustained immune dysregulation and post-infectious inflammatory phenotypes in a subset of patients. This narrative review integrates open-access experimental, translational, and clinical data and discusses LD within the spectrum of infection-triggered, immune-mediated processes. We review key immunopathogenic mechanisms, including dysregulated innate immune activation, type I interferon (IFN-I) signaling, T helper 1 and T helper 17 (Th1/Th17) polarization with regulatory T-cell (Treg) insufficiency, antigen persistence (notably borrelial peptidoglycan), and pathways linking infection to autoimmunity such as molecular mimicry, epitope spreading, and human leukocyte antigen (HLA)-restricted susceptibility. These mechanisms are integrated with immune-mediated clinical manifestations affecting the central nervous system (CNS), peripheral nervous system (PNS), musculoskeletal system, heart, skin, and hematologic compartment. Finally, we discuss translational implications for diagnosis, biomarker-guided stratification, and emerging therapeutic strategies that extend beyond antimicrobial therapy, while addressing current controversies and limitations. This framework supports a mechanistic model in which Lyme disease-associated morbidity in selected patients reflects persistent immune activation and dysregulated host responses triggered by infection. Full article

Background/Objectives: Bovine viral diarrhea (BVD) is a major infectious disease of cattle caused by bovine viral diarrhea virus genotypes 1 and 2 (BVDV-1 and BVDV-2). Current inactivated and live attenuated vaccines provide incomplete cross-genotype protection and may exhibit limitations related to durability of immunity or safety. This study evaluated whether co-expression of the BVDV envelope glycoproteins E1 and E2 in a Modified Vaccinia Ankara (MVA) vector could support antigen expression and induce immune responses in a proof-of-concept model. Methods: Recombinant Modified Vaccinia Ankara (MVA) viruses expressing BVDV-1 E1E2 or BVDV-2 E1E2 were generated by homologous recombination. Recombinant viruses were purified and characterized for antigen expression, genetic stability, and growth properties in vitro. Immunogenicity was evaluated in a BALB/c mouse model by measuring E2-specific antibody responses, virus-neutralizing antibodies, and antigen-responsive cellular immune responses. Results: Both recombinant MVA constructs showed detectable E2 expression when E1 and E2 were co-expressed, and exhibited growth characteristics comparable to parental MVA with stable maintenance after serial passage. In contrast, recombinant MVA expressing E2 alone did not yield detectable E2 protein under the same experimental conditions. Immunization induced detectable humoral and cellular immune responses, including E2-specific IgG antibodies, virus-neutralizing antibodies, and increased frequencies of antigen-responsive CD8⁺ T cells with a tendency toward a Th1-biased profile. Conclusions: These findings indicate that co-expression of BVDV E1 and E2 in an MVA vector can support detectable antigen expression and induce measurable immune responses in a mouse proof-of-concept model. Further studies in cattle, including challenge experiments, will be required to determine the protective efficacy and practical applicability of this platform for BVDV vaccine development. Full article

Objectives: This study aimed to investigated the role of Giardia extracellular vesicles (EVs) in intercellular communication and to evaluated their potential as vaccine candidates. Methods: The immunomodulatory effects of Giardia EVs were assessed in mouse macrophages and human monocyte-derived dendritic cells (Mo-DCs), with a particular focus on key inflammatory signaling pathways. In vivo immunogenicity was evaluated following EV administration, and the antigenic composition of EV cargo was characterized by proteomic analysis. Results: Giardia EVs activated pro-inflammatory signaling pathways in mouse macrphages, including SAPK/JNK, ERK1/2, and NF-κB. This activation was associated with IκB-α degradation and nuclear translocation of p65. Furthermore, EV stimulation significantly upregulated the expression of pro-inflammatory genes, including Il1β, Il6, Il4, Ptgs2, Nos2, and Tnf, with log₂ fold changes ranging from 3.9 to 15.8. Consistently, EVs increased iNOS protein expression (28–45%) and nitrite production (9.6–12.3-fold). In human Mo-DCs, Giardia EVs promoted cellular maturation, as evidenced by increased expression of MHC-II, CD80, and CD86, and enhanced T-cell proliferation with a Th1-skewed profile. In vivo immunization induced antigen-specific antibody responses, with IgG subclass distribution indicative of a balanced Th1/Th2 response. Proteomic analysis identified immunoreactive EV-associated proteins, including elongation factor 1-alpha, α-7.3 giardin, tubulin, and variant surface proteins (VSPs), which are well-established antigens in Giardia infection, with prominent bands observed at approximately 22 kDa and 50 kDa. Conclusions: Collectively, these findings demonstrate that Giardia EVs modulate innate immune responses in vitro, elicit antigen-specific humoral immunity in vivo, and contain conserved immunogenic proteins. These properties support their potential as a promising cell-free vaccine platform against giardiasis. Full article

Background/Objectives: Sporotrichosis is an emerging zoonotic subcutaneous fungal infection with limited therapeutic options, highlighting the need for improved immunomodulatory strategies. CTLA-4 is an inhibitory immune checkpoint that negatively regulates T-cell activation. In this study, we evaluated whether a CTLA-4 antisense oligonucleotide (CTLA-4 ASO) is associated with enhanced immune responses to an adjuvanted recombinant Sporothrix sp. enolase antigen (rSsEno) formulation. Methods: CTLA-4 ASO uptake, cytotoxicity, and gene-silencing activity were assessed in murine splenocytes in vitro. BALB/c mice were immunized with rSsEno formulated with Montanide Gel 01, either alone or in combination with 5 µg CTLA-4 ASO. Antigen-specific serum antibody responses were quantified by ELISA. Splenocytes from immunized mice were restimulated with enolase, and cytokine production (IFN-γ, IL-2, IL-17, and TNF-α) was measured using Cytometric Bead Array (CBA). Results: CTLA-4 ASO was efficiently internalized by splenocytes and was associated with reduced expression of CTLA-4 without detectable cytotoxicity in vitro. Mice receiving the ASO-supplemented formulation developed significantly higher anti-enolase antibody titers compared to those immunized with adjuvant alone. Upon antigen restimulation, splenocytes from ASO-treated mice produced higher levels of IFN-γ, IL-2, TNF-α, and IL-17, consistent with an enhanced recall response characterized by a mixed Th1/Th17 cytokine profile. Conclusions: CTLA-4 ASO was associated with an enhanced recall response characterized by a mixed Th1/Th17 cytokine profile. These findings suggest a potential immunomodulatory effect of CTLA-4 targeting. Further studies incorporating dose optimization, infection challenge models, and appropriate sequence controls are required to determine the specificity and relevance of these effects for protective immunity against sporotrichosis. Full article

Temporomandibular disorders (TMDs) are multifactorial conditions traditionally attributed to excessive mechanical loading on the temporomandibular joint, leading to clinical manifestations ranging from joint sounds to structural deformation. Contributing factors include trauma, occlusal abnormalities, psychological stress, and bruxism. However, immune and molecular alterations associated with early disease activity are not systematically integrated into structure-centered TMD frameworks. Emerging evidence indicates that temporomandibular joint osteoarthritis (TMJOA) involves activation of innate immunity caused by damage-associated molecular patterns (DAMPs) generated through mechanical loading, together with non-antigen-specific adaptive immune responses, including macrophage polarization and T helper 17 (Th17) and regulatory T (Treg) cell imbalance. Inflammatory and mechanical inputs converge through shared signaling modules and mechanoresponsive transcriptional programs, promoting extracellular matrix degradation, fibrotic remodeling, and subchondral bone remodeling. This review synthesizes the current immunopathological and mechanobiological evidence and introduces temporomandibular immunologic disease (TMID) as a mechanism-oriented framework, characterized by a reinforcing cycle between mechanically induced tissue damage and immune activation within the temporomandibular joint (TMJ) microenvironment. TMID complements TMJOA and Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) structural diagnostic categories while excluding antigen-specific autoimmune arthritides such as rheumatoid arthritis, thus functioning as a mechanistic overlay framework for the integration of immuno-mechanical signaling networks in immune-active, mechanically driven TMJ pathology. Full article

Background: With the evolving paradigm of vaccine development, microcapsules have attracted considerable research interest as particulate adjuvants over the past decades. However, the rational engineering design of microcapsule-based composite adjuvant systems to elicit robust immune responses remains a significant challenge. Methods: This study developed polylactic acid (PLA) microcapsules with spatiotemporally coupled delivery and immunopotentiator properties. The resulting formulations were assessed for humoral and cellular immune responses in mice. Results: We prepared uniform-sized microcapsules (MC) and formulated them with monophosphoryl lipid A (MPLA) as a composite component (MPLA@MC), with hydrodynamic diameters of 4.58 μm and 4.12 μm, respectively. Such composite adjuvants, when loaded with ovalbumin (OVA) to form OVA@MC and OVA&MPLA@MC, promoted cellular uptake and activation, exhibiting preferred lysosomal escape advantages. For in vivo experiments, microcapsule-based vaccines elevated serum levels of IgG antibody, and OVA&MPLA@MC induced Th1-biased antibody responses. Specifically, OVA&MPLA@MC also elicited strong cellular immune responses compared to other vaccines, as evidenced by increased secretion of Interferon-γ (IFN-γ) in mouse splenocytes and Granzyme B (Gzmb) in T cells. Mechanistically, muscle tissues at the injection site showed that microcapsule-based vaccines enhanced the recruitment for phagocytosis. Meanwhile, bulk RNA sequencing (RNA-seq) confirmed extensive activation of immune responses and related signaling pathways. Conclusions: This rationally designed composite strategy for spatiotemporally coupled delivery serves as a potent platform for orchestrating synergistic immune responses, opening up new avenues for the development of effective therapeutic and anti-infectious vaccines. Full article

The moderate pathogenicity coupled with high host susceptibility of Eimeria maxima has precipitated substantial economic losses in the poultry industry. Addressing challenges such as emerging drug resistance underscores the imperative for innovative vaccine strategies. This study developed a novel DNA vaccine to solve this challenge by fusing E. maxima elongation factor-1α (EmEF1α) with chicken chemokine XCL1 (ChXCL1) in the pVAX1 vector. The recombinant plasmid, designated pVAX1-ChXCL1-EmEF1α, was successfully constructed and confirmed to express the ChXCL1-EmEF1α fusion protein in vitro. Immunization of chickens with this DNA vaccine elicited a robust and balanced immune response, characterized by significantly increased proportions of CD4⁺ (11.76%) and CD8⁺ (5.58%) T lymphocytes, elevated levels of Th1-associated cytokines (IFN-γ and IL-12), and strong antigen-specific IgG and IgA antibody responses. Following experimental challenge with E. maxima, vaccinated birds exhibited substantial protection: a 66.4% reduction in oocyst shedding, a 71.7% improvement in relative weight gain, marked attenuation of intestinal lesions, and an anticoccidial index (ACI) of 170. These findings demonstrate that the ChXCL1-EmEF1α DNA vaccine effectively enhances both cellular and humoral immunity. Collectively, this study validates ChXCL1 as a potent molecular adjuvant and establishes the “antigen–adjuvant” fusion DNA platform as a promising strategy for developing next-generation vaccines against avian coccidiosis. Full article

Gut dysbiosis, defined as a disruption in the structure or function of the intestinal microbiota, is increasingly recognized as a key contributor to inflammatory, metabolic, and neuropsychiatric diseases. Conventional interventions such as broad-spectrum antibiotics, generic probiotics, and fecal microbiota transplantation (FMT) often show limited and inconsistent efficacy because they lack specificity, durability, and robust safety controls. In contrast, recent advances in DNA-based technologies are reshaping the therapeutic landscape by enabling targeted, programmable, and mechanistically informed modulation of the gut ecosystem. This review presents an integrated overview of three major domains driving this shift: CRISPR-based systems that selectively delete, silence, or reprogram microbial genes; synthetic biology-driven live therapeutics engineered to sense disease-associated cues and execute controlled responses; and metagenomics-informed strategies that tailor interventions to patient-specific microbial gene profiles and functional deficits. Additionally, we examine the continued evolution of FMT toward DNA-optimized workflows and defined microbial consortia that offer safer, more standardized alternatives to crude donor material. Across these domains, we discuss delivery platforms (including bacteriophages, conjugative plasmids, extracellular vesicles, and synthetic nanoparticles), and compare their efficiency, specificity, and scalability. We further highlight how DNA-guided interventions interface with host immunity—shaping Treg/Th17 balance, mucosal barrier function, and inflammatory signaling—while also analyzing ecological and evolutionary risks, biocontainment strategies, and regulatory classification gaps that will govern clinical translation. Together, these developments signal a transition from empirical microbiome manipulation to rational ecosystem engineering. DNA-guided therapies hold strong promise for precise and personalized management of gut-related diseases, but their success will depend on rigorous ecological risk assessment, long-term monitoring, and adaptive regulatory frameworks alongside continued technological innovation. Full article

The immune system is a pivotal regulator of reproductive physiology, maintaining tissue homeostasis essential for successful pregnancy while contributing to infertility and reproductive disorders when dysregulated. Natural products represent a valuable source of novel immunomodulatory agents. Icariin (ICA), a prenylated flavonoid glycoside isolated from Epimedium species (Horny Goat Weed), has a long-standing traditional use for “invigorating yang,” which modern research attributes to its reproductive function-enhancing properties. This review synthesizes emerging evidence that the beneficial effects of ICA on female and male reproductive health are primarily mediated through its sophisticated immunomodulatory actions on the reproductive–immune axis. We systematically dissect the molecular mechanisms by which ICA reprograms the reproductive immune microenvironment, focusing on its regulation of macrophage polarization, T-helper cell (Th1/Th2/Th17) and regulatory T-cell (Treg) balance, and suppression of key pro-inflammatory signaling pathways (NF-κB, NLRP3 inflammasome, JAK-STAT) in ovarian, uterine, and testicular tissues. This review provides a detailed account of how ICA modulates reproductive disorders via regulating immune responses, with the aim of offering innovative strategies for the design of novel immunomodulatory therapies targeting reproductive diseases. Full article

Background: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections and poses a substantial disease burden to infants, older adults, and immunocompromised populations. Methods: In this study, a recombinant vaccinia virus (rMVA-RSV preF) was constructed based on the modified vaccinia virus Ankara (MVA) platform by inserting a stabilized prefusion F protein gene of RSV into the MVA genome. The immunogenicity of rMVA-RSV preF and preF protein was evaluated in Balb/c mice under different vaccination regimens. Results: A heterologous prime–boost regimen, priming with rMVA-RSV preF and boosting with AS01E-adjuvanted preF protein, elicited robust cellular and humoral immune responses with a Th1 bias. This regimen significantly enhanced immunogenicity compared to homologous vaccination. Conclusions: There is a lack of data from further challenge studies to support the efficacy of the rMVA-RSV preF vaccine in terms of protection, but our findings demonstrate a favorable immunogenicity profile of the rMVA-RSV preF vaccine, supporting its further development as a promising RSV vaccine candidate. Full article

Leptospirosis is a neglected zoonosis causing significant economic losses in livestock, primarily through Bovine Genital Leptospirosis (BGL). While current vaccines prevent clinical disease, they typically fail to provide sterilizing immunity against adapted strains. This allows Leptospira to persist in the genitourinary tract, maintaining environmental shedding and zoonotic risk. Achieving sterilizing immunity remains a challenge, and this gap may be closely related to the immune response pattern of ruminants, where effective protection against chronic colonization requires, besides the humoral response, a robust cellular immune response (Th1/IgG2). Recent studies indicate that adjuvants based on oil emulsions or biodegradable polymers are better at inducing Th1/IgG2 responses and the proliferation of CD4⁺ T cells, as well as WC1⁺ γδ T cells, which may be essential for eliminating Leptospira from renal and probably also genital tissues. Thus, overcoming chronic colonization through inducing the Th1-type immune response may be the main challenge for vaccination to fulfill its role in sustaining herd immunity and mitigation of zoonotic risk, in line with the One Health approach. In this context, we aimed to critically examine immune mechanisms in ruminants, advances in vaccine platforms and adjuvant strategies against bovine leptospirosis and outline the challenges that must be overcome to achieve sterilizing immunity. Full article