Search Results (396)

Background: Infectious bronchitis virus (IBV) is a gammacoronavirus that causes a highly contagious disease in chickens and seriously endangers the poultry industry. The GI-19 is a predominant lineage. However, no effective commercially available vaccines against this virus are available. Methods: In this present study, the CHO eukaryotic and the E.coli prokaryotic expression system were used to express S1-SpyTag and AP205-SpyCatcher, respectively. Subsequently, the purified S1-SpyTag and AP205-SpyCatcher were coupled to form the nanoparticles AP205-S1 (nAP205-S1) in PBS buffer at 4 °C for 48 h. S1-SpyTag and nAP205-S1 were formulated into vaccines with white oil adjuvant and employed to immunize 1-day-old SPF chickens for the comparative evaluation of their immune efficacy. Results: The nAP205-S1 vaccine in chickens induced robust IBV-specific humoral and cellular immune responses in vivo. Importantly, the humoral and cellular immune responses elicited by the nAP205-S1 vaccine were more robust than those induced by the IBV S1-SpyTag vaccine at both the same dose and double the dose, with a notably significant difference observed in the cellular immune response. Furthermore, experimental data revealed that chicken flocks vaccinated with nAP205-S1 achieved 100% group protection following a challenge, exhibiting a potent protective immune response and effectively inhibiting viral shedding. Conclusions: These results reveal the potential of developing a novel nanoparticle vaccine with broadly protective immunity against GI-19 IBV. Full article

Background: The longitudinal RisCoin study investigated risk factors for COVID-19 vaccination failure among healthcare workers (HCWs) and patients with inflammatory bowel disease (IBD) at a University Hospital in Germany. Since the hospital served as the study sponsor and employer of the HCW, we implemented a custom mobile application. We aimed to evaluate the implementation, adherence, benefits, and limitations of this study’s app. Methods: The app allowed secure data collection through questionnaires, disseminated serological results, and managed bidirectional communication. Access was double-pseudonymized and irreversibly anonymized six months after enrollment. Download frequency, login events, and questionnaire submissions between October 2021 and December 2022 were analyzed. Multivariable logistic regression identified factors associated with app adherence. Results: Of the 3979 participants with app access, 3622 (91%) used the app; out of these, 1016 (28%) were “adherent users” (≥12 submitted questionnaires). App adherence significantly increased with age. Among HCW, adherent users were more likely to be non-smokers (p < 0.001), working as administrators or nursing staff vs. physicians (p < 0.001), vaccinated against influenza (p < 0.001), and had not travelled abroad in the past year (p < 0.001). IBD patients exposed to SARS-CoV-2 (p = 0.0133) and those with adverse events following the second COVID-19 vaccination (p = 0.0171) were more likely adherent app users. Despite technical issues causing dropout or non-adherence, the app served as a secure solution for cohort management and longitudinal data collection. Discussion: App-based cohort management enabled continuous data acquisition and individualized care while providing flexibility and anonymity for the study team and participants. App usability, technical issues, and cohort characteristics need to be thoroughly considered prior to implementation to optimize usage and adherence in clinical research. Full article

Mucosal immunization represents a promising strategy for preventing enteric infections. Rotavirus (RV), a leading gastrointestinal pathogen distinguished by its remarkable stability and segmented double-stranded RNA genome, has been engineered into a versatile oral vaccine vector through advanced reverse genetics systems. The clinical efficacy of live-attenuated RV vaccines highlights their unique capacity to concurrently induce mucosal IgA responses and systemic neutralizing antibodies, positioning them as a multiple action vector for multiple immune protection. In this review, we summarize the RV colonization of the intestine and stimulation of intestinal immunity, as well as recent advancements in RV reverse genetics, and focus on their application in the rational design of a multivalent mucosal vaccine vector targeting enteric pathogens considering the advantages and challenges of RV as a vector. We further propose molecular strategies to overcome genetic instability in recombinant RV vectors, including the codon optimization of heterologous inserts. These insights provide a theoretical foundation for developing next-generation mucosal immunization platforms with enhanced safety, stability, and cross-protective efficacy. Full article

Background:Salmonella Typhimurium is a major zoonotic pathogen, in which type 1 fimbriae play a crucial role in intestinal colonization and immune modulation. This study aimed to improve the protective immunity of a previously developed growth-deficient strain—a double auxotroph for D-glutamate and D-alanine—by engineering the inducible expression of type 1 fimbriae. Methods: P_tetA-driven expression of the fim operon was achieved by λ-Red mutagenesis. fimA expression was quantified by qRT-PCR, and fimbriation visualized by transmission electron microscopy. Adhesive properties were evaluated through FimH sequence analysis, yeast agglutination, mannose-binding/inhibition assays, and HT-29 cell adherence. BALB/c mice were immunized orogastrically with IRTA ΔΔΔ or IRTA ΔΔΔ P_tetA::fim. Safety and immunogenicity were assessed by clinical monitoring, bacterial load, fecal shedding, ELISA tests, and adhesion/blocking assays using fecal extracts. Protection was evaluated after challenging with wild-type and heterologous strains. Results: IRTA ΔΔΔ P_tetA::fim showed robust fimA expression, dense fimbrial coverage, a marked mannose-sensitive adhesive phenotype and enhanced HT-29 attachment. Fimbrial overexpression did not alter intestinal colonization or translocation to mesenteric lymph nodes (mLNs). Immunization elicited a mixed IgG1/IgG2a, significantly increased IgA and IgG against type 1 fimbriae-expressing Salmonella, and enhanced the ability of fecal extracts to inhibit the adherence of wild-type strains. Upon challenge (IRTA wild-type/20220258), IRTA ΔΔΔ P_tetA::fim reduced infection burden in the cecum (−1.46/1.47-log), large intestine (−1.35/2.17-log), mLNs (−1.32/0.98-log) and systemic organs more effectively than IRTA ΔΔΔ. Conclusions: Inducible expression of type 1 fimbriae enhances mucosal immunity and protection, supporting their inclusion in next-generation Salmonella vaccines. Future work should assess cross-protection and optimize FimH-mediated targeting for mucosal delivery. Full article

Background: The emergence of checkpoint inhibitors (CPIs) has significantly improved survival outcomes in later-stage melanoma. However, the efficacy of these treatments remains limited, with around 50% of later-stage melanoma patients experiencing recurrence. As variable response rates to CPIs persist, the development of cancer vaccines has emerged as a potential strategy to augment antitumor immune responses. Results: This review compares two promising personalized therapeutic cancer vaccine trials in advanced melanoma: Elios Therapeutics’ Tumor Lysate (TL) vaccine and Moderna’s mRNA-4157 vaccine. The TL vaccine, which utilizes yeast cell wall particles (YCWPs) loaded with autologous tumor lysate, and the mRNA-4157 vaccine, which encodes up to 34 patient-specific neoantigens, both aim to stimulate robust tumor-specific immune responses. Both trials were phase 2b randomized studies, with Elios Therapeutics’ trial employing a double-blind, placebo-controlled design, while Moderna’s was open-label. Both trials had roughly equivalent sample sizes (n = 187 and n = 157, respectively) with similar demographics and disease characteristics. The TL trial reported improvements in disease-free survival (DFS) with a hazard ratio (HR) of 0.52 (p < 0.01) over 36 months, whereas the mRNA-4157 trial demonstrated improvements in recurrence-free survival (RFS) with an HR of 0.56 (p = 0.053) over 18 months. The TL vaccine exhibited lower rates of related grade 3 adverse events (<1%) compared to the mRNA vaccine (12%). Key differences between the two trials include the use of CPIs, with 100% of patients in the mRNA trial receiving pembrolizumab versus 37% of the patients in the TL trial receiving either an anti-PD-1 or anti-CTLA-4. The production processes also varied significantly, with the mRNA vaccine requiring individualized sequencing and a 9-week production time, while the TL vaccine utilized tumor lysate with a 1–3-day production time. Conclusions: While both vaccines demonstrated promising efficacy, future phase 3 trials are needed to further evaluate their potential as adjuvant therapies for melanoma. This review highlights the comparative strengths and limitations of these vaccine platforms, providing insight into the evolving landscape of adjuvant cancer vaccines. Full article

Background/Objectives: This retrospective observational study investigated coronavirus disease 2019 (COVID-19)-related mortality trends in the US throughout the pandemic. Methods: We performed a retrospective, descriptive analysis between 2020 and 2024 using data from the US National Center for Health Statistics. Results: The total number of COVID-19 deaths rose by 19% from 2020 to 2021, followed by a significant decline in the subsequent years, with an average reduction factor of 0.44. Mortality rates remained higher in males compared to females, with a gender disparity between 52 and 62%. Age-specific crude mortality rates increased with advancing age, with higher mortality observed in older populations. However, crude death rates significantly declined across all ages except for the 1–4 years group, which experienced a 33% increase. The majority of fatalities occurred in medical facilities (63–80%), but this proportion gradually decreased over time, while the percentage of deaths occurring at home nearly doubled from 2020 to 2024 (6% to 11%). Conclusions: The initial mortality peak for COVID-19 was followed by a substantial decline, likely influenced by the widespread availability of vaccines, improvements in clinical management, and the emergence of less virulent variants. The persistent gender and age disparities, alongside the fluctuating distribution of the places of death, offer insights for refining healthcare policies and optimizing resource allocation in this and other future pandemics. Full article

Background: pGX9501 is a prophylactic DNA vaccine encoding the spike protein of SARS-CoV-2 and can induce immune response in the human body so as to prevent COVID-19. With respect to non-clinical studies, pGX9501 has been demonstrated to induce both cellular and humoral immune responses in various animal models. It was found that the level of antibody titers following a two-dose regimen was higher than that following a single-dose regimen in nonhuman primate challenge model. Methods: In China, a phase I, randomized, double-blind, placebo-controlled clinical trial has been conducted in Huashan Hospital, Shanghai, China to evaluate the safety, tolerability, and immunogenicity of DNA vaccine pGX9501 administered intradermally (ID) followed by electroporation (EP) in 45 Chinese healthy volunteers aged 18 to 59 years old. Results: No adverse events of special interest (AESIs), death, or treatment-related SAEs occurred in this study. All the treatment-related (vaccine or EP) adverse events (TRAEs) were of grade 1 and 2 in severity. The solicited AEs were reported in thirty-two (32/36, 88.9%) and nine (9/9, 100.0%) subjects, respectively, in the DNA vaccine and placebo group. The frequency of solicited AEs did not increase with vaccine dose level and frequency. The DNA vaccine pGX9501 effectively enhanced both humoral and cellular immune responses in a dose-dependent manner, with increased antibody GMTs and peak seroconversion rates observed on day 42. The significant rise in IFN-γ levels confirmed the vaccine’s ability to induce cellular immune responses. Variations in the microbiome structure suggested a tangible impact of the gut microbiota on vaccine immunogenicity. Conclusions: The findings from this study confirm the immunogenicity and safety of the DNA vaccine pGX9501 and point to the potential role of the gut microbiota in vaccine immune responses. These insights provide practical references for the future design and development of DNA vaccines. Full article

Background: Live attenuated and inactivated virus vaccines are commonly used against infectious bronchitis virus (IBV) in chickens, but they have limitations such as mutation risks and short efficacy. This study explores cationic bovine serum albumin (BSA) polyamine nanoparticles (NPs) for delivering IBV spike protein mRNA, aiming to develop a safer and more effective vaccine. Methods: A BSA-based nanoparticle system was designed with positive surface charges and characterized using dynamic light scattering (DLS), Zetasizer, and transmission electron microscopy (TEM). Its cytotoxicity, cellular uptake, and ability to deliver IBV spike protein mRNA were evaluated in macrophage-like chicken cell lines (HD11), followed by immunogenicity studies in SPF chickens to assess immune responses. Results: The study demonstrated successful binding and transfection efficiency of the in vitro transcription (IVT)-mRNA complexed with the NPs, which was enhanced with chloroquine. Immunogenicity studies in SPF chickens showed a significant increase in antibody titers in chickens vaccinated with the mRNA vaccine compared to the PBS control, indicating an effective immune response against the IBV S protein. Furthermore, the neutralization index doubled after a higher-dose mRNA booster with chloroquine, and PBMCs from immunized chickens exhibited a threefold higher stimulation index than the PBS control. Conclusions: BSA-based NPs effectively deliver IBV spike protein mRNA, enhancing immune responses and offering a promising strategy for a safer, more effective IBV vaccine. Full article

Background/Objectives: The combination of a hemagglutinin antigen (HA)-based inactivated influenza vaccine (IIV; Fluarix^® Tetra; GlaxoSmithKline) with a nucleoprotein (NP)-based vaccine, such as OVX836, should increase the efficacy of influenza vaccines since it leverages two complementary immunological mechanisms: HA antibodies targeting the virus envelope and neutralizing it, and an NP cell-mediated immune (CMI) response destroying infected cells. Methods: This was a randomized, double-blind, Phase 2a study (ClinicalTrials.gov NCT05284799) including three groups of 60 healthy subjects (18–55 years old) receiving either IIV + placebo, IIV + OVX836 (480 µg), or OVX836 + placebo intramuscularly and concomitantly into the same deltoid muscle. The endpoints were reactogenicity, safety, and immunogenicity (hemagglutination inhibition assay [HAI], anti-NP immunoglobulin G [IgG], and NP-specific cell-mediated immunity [CMI]). Results: The co-administration of IIV + OVX836 was safe and well-tolerated. The HAI response was strong and similar in the two IIV groups with no interference of OVX836. The humoral anti-NP IgG and NP-specific CMI responses to OVX836 were strong in the two OVX836 groups, and no major interference of IIV was observed. Conclusions: This study supports further clinical development of OVX836 as a combined IIV/OVX836 seasonal vaccine capable of inducing robust and complementary HAI and CMI NP-specific responses. Full article

Nanoclays have gained attention in biological applications due to their biocompatibility, low toxicity, and cost-effectiveness. Layered double hydroxides (LDHs) are synthetic nanoclays that have been used as adjuvants and antigen carriers in nanovaccines developed through passive bioconjugation. However, performing active bioconjugation to bind antigens covalently and generate subunit nanovaccines remains unexplored. In this study, we investigated the synthesis, functionalization, and active conjugation of LDH nanoparticles to produce subunit nanovaccines with peptides from SARS-CoV-2. The synthesis of Mg-Al LDHs via a coprecipitation and hydrothermal treatment rendered monodisperse particles averaging 100 nm. Their functionalization with (3-aminopropyl)triethoxysilane was better than it was with other organosilanes. Glutaraldehyde was used as a linker to bind lysine as a model biomolecule to establish the best conditions for reductive amination. Finally, two peptides, P₂ and P₅ (epitopes of the SARS-CoV-2 spike protein), were bound on the surface of the LDH to produce two subunit vaccine candidates, reaching peptide concentrations of 125 and 270 µg/mL, respectively. The particles were characterized using DLS, TEM, XRD, TGA, DSC, and FTIR. The cytotoxicity studies revealed that the conjugate with P₂ was non-toxic up to 250 µg/mL, while the immunogenicity studies showed that this conjugate induced similar IgG titers to those reached when aluminum hydroxide was used as an adjuvant. Full article

Porcine peripheral blood mononuclear cells (pPBMCs) are increasingly recognized as a valuable model in biomedical and translational research, particularly in contexts directly related to human health and disease. Their immunological features, such as the presence of CD4⁺CD8⁺ double-positive T cells and cytokine expression patterns, exhibit a notable degree of similarity to human immune cells, making them an attractive tool for studying human-relevant immune responses. This review outlines current methodologies for isolating and cryopreserving pPBMCs, with a focus on maintaining high cell viability and functionality. Key technical considerations, including the optimal use of gradient media, appropriate anticoagulants, and standardized freezing/thawing protocols, are discussed in detail. Furthermore, the article highlights the applications of pPBMCs in various research contexts, including vaccine development, inflammation studies, infection models, and xenotransplantation. A comparative perspective is provided to identify similarities and differences between porcine and human PBMCs, supporting the validity of swine as a translational model. Evidence from pPBMC-based studies has shown predictive value for human outcomes, reinforcing their role as a surrogate system for preclinical investigations. Given their anatomical, physiological, and immunogenetic similarities to humans, porcine PBMCs represent a valuable bridge between basic science and clinical application, playing an increasingly important role in translational medicine. Full article

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

Airborne diseases pose a significant challenge in intensive livestock farming due to their rapid transmission. Aerosols facilitate the spread of pathogens, introducing external infections to farms and enabling cross-transmission within barns. To address knowledge gaps in aerosol dynamics in animal respiratory tracts and enhance understanding of airborne disease transmission, this study employed CT scanning, 3D printing, and CFD technologies to develop and validate a pig respiratory model. Qualitative and quantitative results from the present study reveal spatiotemporal heterogeneity in aerosol deposition and transmission. Under rest conditions, for aerosols with D ≤ 5.0 μm, 21.1% of inhaled aerosols were deposited in the lung by the end of a respiratory cycle. Doubling the respiratory cycle or the inhalation rate could further increase the penetration ability of small-sized aerosols by approximately 60% to 70%. Moreover, the asymmetric distribution of airflow between the left and right halves of the lower respiratory tract (Q_L/R = 0.89) resulted from the leftward position of the pig’s heart and consequently led to a deposition ratio of about 0.83 between the left and right bronchial airways. These findings provide fundamental scientific data for the development and application of aerosolized vaccines and offer insights into optimizing respiratory intervention strategies. Full article

Background/Objectives: Rising antibiotic resistance underscores the urgent need for effective vaccines against shigellosis. Our previous research identified the Shigella flexneri 2a truncated mutant (STM), a wzy gene knock-out strain cultivated in shake-flasks, as a promising broadly protective Shigella vaccine candidate. Expanding on this finding, our current study explores the feasibility of transitioning to a fermentor-grown STM as a vaccine candidate for further clinical development. Methods: The STM and STM-Cj, engineered to express the conserved Campylobacter jejuni N-glycan antigen, were grown in animal-free media, inactivated with formalin, and evaluated for key antigen retention and immunogenicity in mice. Results: The fermentor-grown STM exhibited significantly increased production yields and retained key antigens after inactivation. Immunization with the STM, particularly along with the double-mutant labile toxin (dmLT) adjuvant, induced robust immune responses to the conserved proteins IpaB, IpaC, and PSSP-1. Additionally, it provided protection against homologous and heterologous Shigella challenges in a mouse pulmonary model. The STM-Cj vaccine elicited antibody responses specific to the N-glycan while maintaining protective immune responses against Shigella. These findings underscore the potential of the fermentor-grown STM as a safe and immunogenic vaccine platform for combating shigellosis and possibly other gastrointestinal bacterial infections. Conclusions: Further process development to optimize growth and key antigen expression as well as expanded testing in additional animal models for the assessment of protection against Shigella and Campylobacter are needed to build on these encouraging initial results. Ultimately, clinical trials are essential to evaluate the efficacy and safety of STM-based vaccines in humans. Full article

Cervical cancer (CC) is the only cancer that has the possibility of primary and secondary prevention. Despite this, it is one of the leading causes of cancer death among women, especially in developing countries. The World Health Organization has set the ambitious goal of eliminating CC by 2030 by suggesting specific types of intervention. Unfortunately, to date, we are very far from this goal at a global level, including developed countries. Implementing vaccination coverage among the target population is one of the strategies to be pursued in this area. Achieving this goal should include combating misinformation about the HPV vaccine, which is one of the main reasons for vaccination hesitancy. Such conspiracy theories are prevalent on social media, one of the primary sources of information for adults and adolescents today. In this regard, the Internet plays a significant role in disseminating information about the HPV vaccine, both positively and negatively. The Internet provides easy access to information about the HPV vaccine, including its safety, efficacy, recommended dosing schedule, and potential side effects. It may promote vaccine advocacy and debunking vaccine myths. On the other hand, the Internet may be the place for disseminating misinformation and influencing vaccine decision making. It is a double-edged sword in shaping public discourse and perceptions about the HPV vaccine. This overview aims to assess the literature on this topic in depth to promote evidence-based information, analyze the social channels through which misinformation spreads, and leverage digital health interventions essential for promoting HPV vaccination and reducing the burden of HPV-related diseases. Full article