Search Results (1,698)

Background and Objectives: The administration of oral vaccines offers a potential strategy for cancer immunotherapy; yet, the development of effective platforms continues to pose a difficulty. This study examines Escherichia coli Nissle 1917 (EcN) as a microbial vector for the precise delivery of Glypican-1 (GPC1), a tumor-associated antigen significantly overexpressed in pancreatic ductal adenocarcinoma (PDAC).To evaluate the effectiveness of EcN as a vector for the delivery of GPC1 and assess its potential as an oral vaccination platform for cancer immunotherapy. Materials and Methods: EcN was genetically modified to produce a GPC1-flagellin fusion protein (GPC1-FL) to augment antigen immunogenicity. The expression and stability of GPC1 were confirmed in modified PANC02 cells using Western blot and flow cytometry, indicating that GPC1 expression did not influence tumor cell growth. A mouse model was employed to test immunogenicity post-oral delivery, measuring systemic IgG, IL-10, IL-2, and IFN-γ levels to indicate immune activation. Results: Oral immunization with EcN GPC1-FL elicited a robust systemic immune response, demonstrated by markedly increased levels of IgG and IL-10. IL-2 and IFN-γ concentrations were elevated in vaccinated mice relative to controls; however, the differences lacked statistical significance. Western blot examination of fecal samples verified consistent antigen expression in the gastrointestinal tract, indicating effective bacterial colonization and antigen retention. No detrimental impacts were noted, hence substantiating the safety of this methodology. Conclusions: These findings confirm EcN as a feasible and patient-friendly oral vaccination platform for cancer immunotherapy. The effective production of GPC1 in tumor cells, along with continuous antigen delivery and immune activation, underscores the promise of this approach for PDAC and other cancers. This study promotes microbial-based antigen delivery as a scalable, non-invasive substitute for traditional vaccine platforms. Full article

Background: Lipid nanoparticles (LNPs) have proven effective in delivering RNA-based modalities. Rapid approval of the COVID-19 vaccines highlights the promise of LNPs as a delivery platform for nucleic acid-based therapies and vaccines. Nevertheless, improved LNP designs are needed to advance next-generation vaccines and other gene therapies toward greater clinical success. Lipid components and LNP formulation excipients play a central role in biodistribution, immunogenicity, and stability. Therefore, it is important to understand, identify, and assess the appropriate lipid components for developing a safe and effective formulation. Herein, this study focused on developing a novel Polysorbate-80 (PS-80)-based LNP. We hypothesized that substituting conventional linear PEG-lipids with PS-80, a widely used, biocompatible injectable surfactant featuring a branched PEG-like structure, may change the LNPs biodistribution pattern and enhance long-term stability. By leveraging PS-80’s unique structural properties, this study aimed to develop an mRNA-LNP platform with improved extrahepatic delivery and robust freeze/thaw tolerance. Methods: We employed a stepwise optimization to establish both the lipid composition and formulation buffer to yield a stable, high-performing PS-80-based SARS-CoV-2 mRNA-LNP (SC2-PS80 LNP). We compared phosphate- versus tris-based buffers for long-term stability, examined multiple lipid ratios, and evaluated the impact of incorporating PS-80 (a branched PEG-lipid) on in vivo biodistribution. Various analytical assays were performed to assess particle size, encapsulation efficiency, mRNA purity, and in vitro potency of the developed formulation and a humanized mouse model was used to measure its immunogenicity over six months of storage at −80 °C. Results: Replacing the standard 1,2-dimyristoyl-rac-glycero-3-methoxy polyethylene glycol-2000 (PEG-DMG) lipid with PS-80 increased spleen-specific expression of the mRNA-LNPs after intramuscular injection. Formulating in a tris-sucrose-salt (TSS) buffer preserved the LNP’s physicochemical properties and in vitro potency over six months at −80 °C, whereas a conventional PBS-sucrose (PSS) buffer was less protective under frozen conditions. Notably, TSS-based SC2-PS80 LNPs elicited potent humoral immunity in mice, including high anti-spike IgG titers and robust pseudovirus neutralization, comparable to freshly prepared formulations. Conclusions: A PS-80-based mRNA-LNP platform formulated in TSS buffer confers improved extrahepatic delivery, long-term frozen stability, and strong immunogenicity against SARS-CoV-2 following six months. These findings offer a promising pathway for the design of next-generation mRNA vaccines and therapeutics with enhanced stability and clinical potential. Full article

Background: Endoplasmic reticulum (ER)-targeted phototherapy has emerged as a promising approach to amplify ER stress, induce immunogenic cell death (ICD), and enhance anti-tumor immunity. However, its impact on the antigenicity of dying tumor cells remains poorly understood. Methods: Laser activation of the ER-targeted photosensitizer ER-Cy-poNO₂ was performed to investigate its effects on tumor cell antigenicity. Transcriptomic analysis was carried out to assess gene expression changes. Immunopeptidomics profiling was used to identify high-affinity major histocompatibility complex class I (MHC-I) ligands. In vitro functional studies were conducted to evaluate dendritic cell maturation and T lymphocyte activation, while in vivo experiments were performed by combining the identified peptide with poly IC to evaluate anti-tumor immunity. Results: Laser activation of ER-Cy-poNO₂ significantly remodeled the antigenic landscape of 4T-1 tumor cells, enhancing their immunogenicity. Transcriptomic analysis revealed upregulation of antigen processing and presentation pathways. Immunopeptidomics profiling identified multiple high-affinity MHC-I ligands, with IF4G3_986–994 (QGPKTIEQI) showing exceptional immunogenicity. In vitro, IF4G3_986–994 promoted dendritic cell maturation and enhanced T lymphocytes activation. In vivo, the combination of IF4G3_986–994 with poly IC elicited robust anti-tumor immunity, characterized by increased CD8⁺ T lymphocytes infiltration, reduced regulatory T cells (Tregs) in the tumor microenvironment, elevated systemic Interferon-gamma (IFN-γ) levels, and significant tumor growth inhibition without systemic toxicity. Conclusions: These findings establish a mechanistic link between ER stress-driven ICD, immunopeptidome remodeling, and adaptive immune activation, highlighting the potential of ER-targeted phototherapy as a platform for identifying immunogenic peptides and advancing peptide-based cancer vaccines. Full article

Background: Epstein-Barr virus (EBV) infects approximately 95% of the global population, causing numerous malignancy-related cases annually and some autoimmune diseases. EBV-encoded gp350, gH, gL, gp42 and gB glycoproteins are identified as antigen candidates for their key role in viral entry, and nanoparticle vaccines displaying them were developed for the advantage of inducing cross-reactive B cell responses. Methods: To develop liposomes displaying nanoparticle vaccine, we synthesized liposomes to present the well-identified EBV-encoded gp350D₁₂₃ glycoprotein on their surface to imitate the viral structure, through the conjugation between N-hydroxysuccinimide (NHS) groups on the liposomes and primary amine of antigens to form stable amide bond. Then we assessed the immunogenicity of the biomimetic Lipo-gp350D₁₂₃ nanoparticle vaccine in Balb/c mice immunized experiments. Results: The results showed that the sera samples from Lipo-gp350D₁₂₃ nanoparticle vaccine immunized mice collected at weeks 8, 10 and 12 had higher titers of gp350D₁₂₃ protein-specific antibodies, compared to monomer gp350D₁₂₃ protein control, and higher titers of neutralizing antibodies to block EBV-GFP infection in AKATA cells. Meanwhile, the Lipo-gp350D₁₂₃ nanoparticle vaccine also induced higher percentage of CD8+ IFN-γ+ T cells in the spleen, but without significance in CD4+ IFN-γ+ T cells, and these isolated splenocytes showed a higher level of secreted IFN-γ. Moreover, no significant histopathological changes were observed in all vaccinated mice. Conclusions: Altogether these data demonstrated that the liposome displaying promoted the immunogenicity of antigens, and the Lipo-gp350D₁₂₃ nanoparticle vaccine candidate had potential application in blocking EBV infection. The liposome nanoparticle was a useful vector for antigen displaying to elicit effective immunity. Full article

Introduction: COVID-19, caused by SARS-CoV-2, has disrupted global health systems, with vaccines being essential to mitigating its impact. Statins, widely prescribed for dyslipidemia, are associated with muscle-related side effects, which may worsen during COVID-19. This study explores the association between statin use, COVID-19 vaccination, and skeletal muscle-related symptoms. Aims: To evaluate the association between statin use and muscle symptoms (pain and creatine kinase (CK) levels) in COVID-19 patients and investigate whether vaccination is associated with changes in these symptoms. Methods: This observational study included 147 symptomatic COVID-19 patients: 74 chronic statin users (SG) and 73 non-users (CG). Vaccination status (unvaccinated, one-dose, or two-dose Pfizer–BioNTech) was recorded. Muscle pain was assessed using the Numerical Rating Scale (NRS), and CK levels were measured. Additional factors, including age, sex, BMI, and smoking status, were analyzed. Statistical tests examined the potential associations between statin use, vaccination, and muscle-related outcomes. Results: Higher CK levels were more frequently reported in SG, with severe rhabdomyolysis occurring slightly more often in the SG (4% vs. 3%). Men had higher CK values, while women appeared to be at greater risk of severe rhabdomyolysis. Older adults (≥65 years) in the SG had significantly higher CK levels. Fully vaccinated individuals had lower CK values and reported less muscle pain, while unvaccinated participants had the highest incidence of CK abnormalities and severe muscle pain. No significant differences in CK levels were observed between SARS-CoV-2 variants. Conclusions: Statin use was associated with elevated CK levels and increased muscle pain severity. Older adults and women appeared more susceptible to severe muscle complications. Full vaccination was linked to lower CK values and reduced muscle symptoms. Further research is needed to confirm these findings. Full article

Background/Objectives: The spread of the COVID-19 pandemic has spurred the development of advanced healthcare tools to effectively manage patient outcomes. This study aims to identify key predictors of mortality in hospitalized patients with some level of natural immunity, but not yet vaccinated, using machine learning techniques. Methods: A total of 363 patients with COVID-19 admitted to Río Hortega University Hospital in Spain between the second and fourth waves of the pandemic were included in this study. Key characteristics related to both the patient’s previous status and hospital stay were screened using the Random Forest (RF) machine learning technique. Results: Of the 19 variables identified as having the greatest influence on predicting mortality, the most powerful ones could be identified at the time of hospital admission. These included the assessment of severity in community-acquired pneumonia (CURB-65) scale, age, the Glasgow Coma Scale (GCS), and comorbidities, as well as laboratory results. Some variables associated with hospitalization and intensive care unit (ICU) admission (acute renal failure, shock, PRONO sessions and the Acute Physiology and Chronic Health Evaluation [APACHE-II] scale) showed a certain degree of significance. The Random Forest (RF) method showed high accuracy, with a precision of >95%. Conclusions: This study shows that natural immunity generates significant changes in the evolution of the disease. As has been shown, machine learning models are an effective tool to improve personalized patient care in different periods. Full article

Rabies is a zoonotic viral disease that is preventable through vaccination. Effective control strategies should follow the “One Health” concept, as targeting zoonotic pathogens at their animal source is the most effective and cost-efficient approach to protecting human health. The aim of this study was to develop and evaluate two third-generation anti-rabies vaccines based on non-replicative viral vectors, MVA and Ad5, both expressing rabies virus (RABV) glycoprotein (MVA-RG and Ad-RG). MVA-RG was produced using a platform developed in our laboratory, while Ad-RG was generated using a commercial kit. Protection against rabies was assessed in a mouse intracerebral (IC) RABV challenge model. Our results demonstrated that both vectors provided protection against RABV. MVA-RG and Ad-RG administered in two homologous doses conferred 60% and 60–100% protection against RABV challenge, respectively. The survival rate was influenced by the viral vector, the dose, and the immunization scheme. Remarkably, to our knowledge, our study is the first to report 100% protection against IC RABV challenge using a non-replicative Ad5 in a homologous immunization scheme. These promising results support future evaluation of this vaccine candidate in target animals. Full article

Background/Objectives: Yersinia pestis is an important zoonotic pathogen responsible for the rare but deadly disease of people with bubonic, septic, or pneumonic forms of plague. The emergence of multidrug-resistant Y. pestis strains has attracted more and more researchers’ attention to the search for molecular targets for antivirulence therapy, including anti-nutritional-virulence therapy. The glnALG operon plays a crucial role in regulating the nitrogen content within a bacterial cell. This operon codes for three genes: the structural gene glnA and the two regulatory genes glnL and glnG. In this study, we tested the effect of the deletion of glnA and glnALG on the pathogenic properties of Y. pestis. Methods: To assess the contribution of nitrogen metabolism to Y. pestis virulence, knockout mutants ΔglnA and ΔglnALG were constructed. The former was unable to synthesize glutamine, while the latter was not only defective in glutamine synthesis but also lacked the two-component sensor–transcriptional activator pair GlnL and GlnG, which could partially compensate for the decrease in intracellular glutamine concentrations by transporting it from the host or by catabolic reactions. For vaccine studies, immunized mice and guinea pigs were injected s.c. with 200 LD₁₀₀ of the wild-type Y. pestis strain. Results: A single knockout mutation in the glnA gene did not affect the virulence of Y. pestis in mice and guinea pigs. Knockout of the entire glnALG gene cluster was required for attenuation in these animals. The ΔglnALG strain of Y. pestis did not cause death in mice (LD₅₀ > 10⁵ CFU) and guinea pigs (LD₅₀ > 10⁷ CFU) when administered subcutaneously and provided 100% protection of animals when subsequently infected with 200 LD₁₀₀ of the Y. pestis virulent wild-type strain 231. Conclusions: Y. pestis, defective in both the glutamine synthetase GlnA and the two-component sensor–transcriptional activator pair GlnL-GlnG, completely lost virulence and provided potent protective immunity to mice and guinea pigs subsequently challenged with a wild-type Y. pestis strain, demonstrating the potential use of the glnALG operon as a new molecular target for developing a safe and efficient live plague vaccine. Full article

Newborns are born with an immature immune system, making them susceptible to infections early in life. Human milk provides essential nutrients and immunological factors that support infant immunity. Maternal vaccination during lactation has the potential to enhance these benefits by triggering an immune response in the mother, potentially extending protection to her child. However, lactating individuals are often excluded from vaccine trials, leading to uncertainties about vaccine safety and efficacy during the postpartum period. This study critically evaluates the effectiveness of vaccines in enhancing the immune-supporting properties of human milk and assesses their safety and efficacy for lactating mothers and their infants. By examining potential benefits alongside safety concerns, we aim to provide a comprehensive understanding of postpartum vaccination’s impact on maternal and infant health. We utilized large-language models (LLMs) to enhance the review process and performed a structured literature search across Ovid/Medline, Embase, and Clarivate Analytics using terms like “breastfeeding”, “postpartum”, and “vaccination”. A three-stage screening process involving human and LLM-assisted evaluation focused on postpartum vaccines and their implications for maternal and infant health. We identified 73 studies covering vaccines against COVID-19, cholera, influenza, pertussis, pneumococcal, rabies, polio, rotavirus, rubella, varicella, typhoid, smallpox, and yellow fever. Most vaccines, such as those for COVID-19 and influenza, appear safe and effective for postpartum use without requiring precautionary measures. However, caution is advised with vaccines such as the yellow fever vaccine, where temporary breastfeeding cessation is recommended. Overall, this review underscores the compatibility of most vaccines with lactation and suggests its benefits for both mother and infant. Full article

The emergence of COVID-19 necessitated the rapid development of vaccines. While highly effective at reducing severe disease and death, breakthrough infections remain a problem as the virus continues to mutate. To help address this issue, we show the utility of a multiplex immunoassay in measuring multiple aspects of the antibody response generated by SARS-CoV-2 vaccines. We use a multiplex immunoassay platform to measure spike-specific IgG concentration, avidity, and receptor-binding inhibition. In addition, we correlate results from an ACE-2 receptor-binding inhibition assay with corresponding data from a SARS-CoV-2 microneutralization assay to establish this inhibitory assay as a potential predictor of virus neutralization. We studied these antibody responses in SARS-CoV-2-naïve and -convalescent vaccinees. Our results showed increased IgG concentrations, avidity, and inhibition following vaccination in both groups. We were also able to differentiate the immune response between the two groups using the multiplex immunoassay platform to look at antibody diversity. The receptor-binding inhibition assay has strong correlations with a cell-based pseudovirus neutralization assay as well as with WT SARS-CoV-2 Washington and Delta variant PRNT₅₀ assays. This suggests that the inhibition assay may be able to simultaneously predict virus neutralization of different SARS-CoV-2 variants. Overall, we show that the developed custom multiplex immunoassay with several experimental variations is a powerful tool in assessing multiple aspects of the SARS-CoV-2 antibody response in vaccinated individuals. Full article

Vaccinations are among the most effective means of preventing hospitalizations related to infections. Despite this, high hospitalization rates for vaccine-preventable diseases strain available healthcare resources and imply deficiencies in primary care. Barriers to vaccinations exist, such as the recent pandemic, vaccine hesitancy, misinformation, and access to care. This study analyzes hospitalization rates due to vaccine-preventable conditions and identifies factors contributing to an increase in these rates in the southeast United States. This study used data from four different data sources. The data covers four pre-pandemic years (2016 to 2019) and the pandemic period (2020 to 2022). The analysis categorized the numbers and rates of hospitalizations for conditions with an available preventative vaccine across three age groups: pre-school aged children, school-aged children, and adults. Comparisons between school- versus non-school-mandated vaccines and a focus on differences between rural versus urban communities, as well as demographic characteristics (i.e., gender, race, and ethnicity), are included. Chi-squared tests were used to assess differences in this descriptive part of the analysis. Linear multiple regression was used to examine the independent influence of geographic location while accounting for potential longitudinal trends and the dimensions of the SVI, including socioeconomic status, household composition, disability, minority status and language, and household type and transportation. The dataset included data from 22,797,826 inpatient episodes, including 32,358 for which the principal reason for hospitalization was a vaccine-preventable condition, not including COVID-19. The analysis shows a consistent pattern characterized by higher rates of hospitalization for counties classified as rural. The pattern holds for preschool age (p < 0.001), school age (p = 0.004), and adults (p = 0.009). The differences are statistically significant in the white population (p = 0.008); in pre-school children, school-age children, and adults (p < 0.001); in females (p = 0.08 in pre-school, and p = 0.013 in adults); and black adults (p = 0.02). The regression results confirmed the findings of the descriptive analysis, indicating significantly higher rates in rural communities. Finally, the regression analysis also showed significantly higher rates associated with greater social vulnerability. This study highlights gaps in vaccination opportunities. These gaps can be seen geographically and in terms of social vulnerability, affected by factors such as poverty, language barriers, household composition, and access to care. Hospitalizations due to immunizable diseases were found to be higher in rural areas, particularly among adults. Communities with a high SVI show a significant increase in hospitalization rates. Community-engaged vaccination outreach programs and state policies could improve vaccination rates, and therefore, public health in rural areas, reducing hospitalizations, and lowering infectious disease risks in these areas. Full article

Porcine epidemic diarrhea (PED) is a severe gastrointestinal disease caused by the porcine epidemic diarrhea virus (PEDV), a virus that spreads through the intestinal tract, leading to significant economic losses in the global swine industry. Therefore, compared to traditional injection method, developing vaccines that effectively stimulate the mucosal immune system to induce a protective immune response is crucial for PED prevention. This study evaluated the immunogenicity of recombinant Lactococcus lactis (L. lactis) strains expressing the PEDV S1 and M proteins (MG1363/pMG36e-S1 and MG1363/pMG36e-M) via oral administration in BALB/c mice and neonatal piglets, assessing cellular, humoral, and mucosal immune responses in the host. The results demonstrated that the recombinant strains significantly stimulated lymphocyte proliferation in mice and increased the proportion of CD3+, CD4+, and CD3+, CD8+ double-positive cells in the spleens of mice and the peripheral blood of piglets (p < 0.05). Furthermore, the recombinant strains significantly increased serum IgG, IgA, and mucosal SIgA levels in piglets (p < 0.05). Meanwhile, serum cytokine levels, including IL-4 and IFN-γ, were significantly elevated in piglets when compared to the control group (p < 0.05). In conclusion, the recombinant L. lactis demonstrated promising potential as a novel live vector vaccine against PEDV. Full article

Background: Annual influenza epidemics pose a significant burden on the global healthcare system. The currently available vaccines mainly induce the production of neutralizing antibodies against hemagglutinin and neuraminidase, which are prone to antigenic variation, and this can reduce vaccine efficacy. Vaccines designed to target T cell epitopes can be potentially valuable. Considering the difficulties in obtaining clinical samples and the unique advantages of mice in disease-related research, a mouse model that can simulate human immune responses can be a superior alternative to peripheral blood mononuclear cells for epitope screening. Methods: The T cell epitopes of the A/California/07/2009 (H1N1) virus were predicted and utilized to evaluate the cellular immune responses of HLA-A2/DR1 and HLA-A11/DR1 transgenic mice during epitope screening. The selected peptides were used to immunize these two groups of transgenic mice, followed by a viral challenge to assess their protective efficacy. Results: The epitopes that were predicted and screened could stimulate cellular immune responses in HLA-A2/DR1 transgenic mice, HLA-A11/DR1 transgenic mice, and C57BL/6 mice. Moreover, the transgenic mice exhibited stronger ability to produce IFN-γ than that of the wild-type mice. Upon immunization and subjecting to viral challenge, the selected peptides exhibited protective effects against the influenza virus. Conclusions: The HLA-A2/DR1 and HLA-A11/DR1 transgenic mouse models can be used for the direct screening and validation of influenza virus T cell epitopes, which is crucial for designing T cell epitope vaccines against influenza viruses. Further, this method can be applied in epitope screening and vaccine designing before the spread of other emerging and sudden infectious diseases, thereby supporting epidemic control. Full article

Introduction: Yellow fever (YF) is a viral hemorrhagic fever transmitted by mosquitoes, characterized by a high mortality due to kidney and liver failure, massive coagulation disorders, and hemorrhages. With no specific treatment, prevention through vaccination and vector control is essential. This study investigates the epidemiology of YF in Brazil from 2011 to 2020, focusing on its trends and distribution across the territory. Methods: This ecological time-series study analyzed confirmed YF cases in Brazil’s 27 federative units between 2011 and 2020. Data were sourced from DATASUS, IBGE, and IPEA. Incidence rates per 100,000 inhabitants were calculated, and various sociodemographic and health indicators were analyzed. Prais–Winsten autoregressive models assessed the trends, while a spatial analysis identified the risk areas using global and local Moran’s I statistics. The data were processed using Stata and GeoDa^® software, version 1.12. Results: YF cases were concentrated in the Amazon and Atlantic Forest biomes. The majority of the cases occurred in males (83.3%), non-white individuals (94.3%), and rural workers. Pará showed an increasing trend in incidence. A higher vaccination coverage correlated with a lower YF incidence, though endemic areas with good vaccination coverage still exhibited high rates. Health and socioeconomic indicators were inversely related to incidence, highlighting disparities in regional development. Conclusion: Effective YF control requires multidisciplinary strategies, including expanded vaccination coverage, intensified vector control, and active surveillance. Research should focus on developing better vaccines, monitoring immunity, and improving the global response coordination. Full article

Background/Objectives: In 2022, the full-scale invasion in Ukraine forced over 6 million Ukrainians, primarily mothers and children, to seek safety outside of the country. This massive influx has posed a significant challenge to the Polish healthcare system, particularly regarding routine vaccination for children. This study aims to examine the vaccination intentions of displaced Ukrainian mothers, their compliance with the Polish National Immunisation Programme (PNIP), and the factors that influence these intentions. Methods: A web-based survey (June–July 2023) was conducted among Ukrainian mothers in Poland. The questionnaire assessed the importance placed on vaccination, knowledge of PNIP, and concerns related to displacement and vaccination. Hierarchical logistic regression identified key determinants. Results: Among 2572 respondents, 64.5% reported that their children had received only some or none of the recommended vaccines. Key barriers included unfamiliarity with PNIP, limited knowledge of vaccines, and concerns about vaccine side effects. Of mothers whose children had not followed PNIP, 41.7% intended to vaccinate, 33.1% refused, and 25.2% were undecided. Regression analysis identified perception of vaccination importance as the strongest predictor. Partial adherence to PNIP doubled vaccination likelihood, while a firm plan to return to Ukraine reduced it 2.4 times. Mistrust in vaccines increased refusal risk tenfold. The final model confirmed mothers’ attitudes towards vaccination and future plans (return to Ukraine) as dominant factors. Conclusions: This study underscores the complex determinants shaping vaccination decisions in conflict-displaced communities. It provides insights for public health strategies to enhance vaccine uptake by reducing access barriers, restoring trust, and strengthening vaccine literacy. Full article