Search Results (3,624)

The genetic and antigenic diversity of H5Nx HPAI Gs/GD lineage continues to be a great challenge facing conventional inactivated vaccines. To overcome this challenge, a recombinant herpes virus of turkey (rHVT) vaccine expressing the viral protein 2 (VP2) of infectious bursal disease (IBD) and H5, rHVT+IBD+H5, was developed using computationally optimized broadly reactive antigen (COBRA) technology. In the current study, the protective efficacy of a commercially available vector trivalent vaccine rHVT+IBD+H5 using COBRA technology was assessed. A total of 120 commercial broilers were divided equally into six groups (G1B–G6B). The chickens in G1B–G3B were challenged with the most recent circulating HPAI-H5N1 clade 2.3.4.4.b Egyptian isolate (GenBank accession No. OQ933425) at 28 days old (DO), while the chickens in G4B and G5B were kept as vaccinated (as G1B and G2B, respectively) and non-challenged, and G6B was the non-vaccinated non-challenged group. In G1B, the chickens were vaccinated with Vaxxitek^® rHVT+IBD+H5 at 1 DO and boostered with a commercially available subunit Baculovirus bivalent inactivated H5+ND (Volvac^® B.E.S.T AI+ND) at 10 DO and had a 100% survival rate. The standalone vaccinated chicken G2B, using rHVT+IBD+H5 at 1 DO, had a highly significant survival rate (90%) vs. 0% (100% mortality) in the non-vaccinated challenged control, G3B. All the vaccinated groups had higher seroconversion at 45 DO especially using H5-coated antigen plates for the enzyme-linked immunosorbent assay (ELISA) test. The viral shedding titers and time were evaluated using a quantitative real-time polymerase chain reaction (RT-qPCR) in the collected oropharyngeal and cloacal swabs at 3, 5, 7, and 10 days post-challenge (DPC). In conclusion, vaccination with rHVT+IBD+H5 either as a standalone or when boostered with subunit Baculovirus bivalent inactivated ND+H5 resulted in 90 and 100% protection, respectively, without significant difference in the quantity and duration of viral shedding between both groups against HPAI-H5N1 clade 2.3.4.4.b experimental challenge in broilers. Full article

Mycoplasma synoviae (MS) poses a continuous threat to the poultry industry in Mainland China, yet a comprehensive nationwide assessment remains lacking. This systematic review and meta-analysis quantified the pooled prevalence of MS and evaluated key epidemiological characteristics and sources of heterogeneity. Peer-reviewed studies were retrieved from multiple databases, and random-effects models were utilized to estimate and compare pooled seroprevalence and molecular detection prevalence. The results revealed a heavy MS infection burden characterized by a distinct diagnostic disparity: a high serological prevalence co-existed with a moderate molecular detection prevalence, reflecting widespread past exposure, chronic carrying, or vaccination. Geographically, the Northwest region exhibited the highest seroprevalence (61.8%), though inter-regional differences were not statistically significant (p = 0.152). Among production types, breeder flocks maintained a relatively high pooled prevalence of 69.6% (95% CI: 40.5–92.0%), although differences among production types were not statistically significant. Subgroup analysis demonstrated a statistically significant difference among age groups; however, the available data did not support definitive conclusions regarding age-specific risk patterns. Breeder flocks exhibited a relatively higher pooled prevalence than layers and broilers, suggesting a potential epidemiological role that warrants further investigation. In conclusion, MS appears to be widely distributed in chickens in mainland China. Differences between the serological and molecular detection results highlight the complexity of interpreting MS prevalence estimates. Given the substantial heterogeneity among studies, the findings should be interpreted cautiously. Future studies incorporating standardized surveillance and detailed vaccination histories are needed to better understand MS epidemiology and support evidence-based control strategies. Full article

Background/Objectives: West Nile virus (WNV) remains a significant threat to human health, with no approved antiviral treatments or vaccine available. A better understanding of the molecular mechanisms governing flavivirus–host interactions is needed to identify host regulatory pathways involved in infection. This study aimed to investigate how WNV infection remodels the host miRNA–mRNA regulatory landscape. Methods: WNV-induced changes in host miRNA expression in HEK-293 cells were profiled using miRNA-Seq. Transcriptome-wide host gene expression changes in WNV-infected cells were analysed using RNA-Seq. Gene Ontology and pathway enrichment analyses were conducted using DAVID. Integrated miRNA–mRNA network reconstruction was performed using Cytoscape based on the experimentally validated miRNA–mRNA interactions in miRNet database. Results: WNV infection induced global changes in host miRNA expression, with pathogenic NY99 and non-pathogenic Kunjin strains of the virus producing overlapping and strain-specific alterations in the miRNA landscape. Transcriptome analysis showed strong induction of interferon-related responses and activation of NF-κB and MAPK signalling pathways in the infected cells. In contrast, pathways associated with RNA processing, splicing, and proteasomal degradation were downregulated. Integrated miRNA–mRNA network analysis identified miR-197-3p, miR-301b-3p, miR-129-3p, miR-3662, and miR-128-5p as candidate regulatory hubs involved in WNV-induced transcriptome remodelling. These networks suggested that miRNA-mediated regulation may influence antiviral signalling, apoptosis, and RNA metabolism during infection. Conclusions: These findings suggest that WNV infection broadly remodels host miRNA–mRNA regulatory networks and identifies candidate miRNAs that may contribute to the regulation of antiviral and cellular stress responses. These predicted regulatory interactions provide a foundation for future experimental validation. Full article

Ranges of distribution of some orthoflaviviruses, including the Omsk hemorrhagic fever virus (OHFV) and the Powassan virus (POWV), have been identified in the range endemic for the tick-borne encephalitis virus (TBEV). In contrast to TBEV, no registered vaccine against OHFV and POWV is currently available. Nevertheless, recent studies have indicated that the anti-TBEV vaccine may offer partial protection against other orthoflaviviruses. The present study assesses OHFV and POWV infection in an experimental model on BALB/c mice one, three- and twelve-months post-immunization with inactivated TBE vaccine. The TBE vaccine was shown to provide long-term protection against OHFV and partial protection against POWV, even in the absence of specific antibodies, and without indications of antibody-dependent enhancement of infection. The neutralizing antibody titer for OHFV in vaccinated animals before and after the challenge with OHFV was similar to the titer of antibodies against the TBEV vaccine strain. Following immunization with anti-TBEV vaccine and subsequent inoculation of POWV, the levels of neutralizing antibodies against the TBEV vaccine strain was observed to be higher compared to those targeting POWV, especially during the initial phase of infection. Such cross-reactive antibodies have potential to pose a significant diagnostic challenge in cases where an infection is occurring simultaneously with an immune response to another virus. Full article

Senecavirus A (SVA) is a newly emerging picornavirus associated with porcine idiopathic vesicular disease and sudden death in newborn piglets. Currently, no specific vaccines or drugs are available against SVA, highlighting the importance of investigating the immunological characteristics of its key proteins. The VP1 protein of SVA exhibits strong immunogenicity and high sequence conservation, and it is indispensable to the viral life cycle. In the present study, a monoclonal antibody (mAb) against VP1 was generated. A series of truncated VP1 proteins was then expressed to precisely map the epitope recognized by this mAb. The minimal reactive unit was identified as ¹⁶DTDFSGELA²⁴. Homology analysis further revealed that this epitope is conserved among different SVA isolates deposited in GenBank. Moreover, AlphaFold prediction, along with PyMOL (Version 3.0.3) and GETAREA analyses, reveals that this epitope resides in the α-helix and loop regions of the three-dimensional structure of the VP1 protein and is surface-exposed. Collectively, these findings indicate that the mAb and its recognized epitope represent valuable tools for investigating SVA etiology and VP1 protein function. Full article

Inflammation plays a pivotal role in the pathogenesis of acne vulgaris, with Cutibacterium acnes recognised as a key etiological agent. The global increase in acne prevalence, coupled with the rising incidence of antibiotic-resistant strains, underscores the necessity for alternative therapeutic strategies. Vaccination has emerged as a promising approach, with various candidates targeting live-attenuated strains and specific virulence factors. Nevertheless, the expanding availability of C. acnes genomic data presents an opportunity to identify previously uncharacterized antigens that hold potential as novel targets for the development of next-generation acne vaccines. Therefore, this study aimed to identify core proteins among C. acnes genomes and evaluate their immunogenicity as potential multi-epitope peptide constructs. In addition, IA1-specific proteins of C. acnes were examined to develop the peptide constructs targeting acne-associated isolates. Pan-core analysis of 609 genomes identified 972 core genes. These genes were subsequently analysed for epitope prediction and antigenicity, and the highly antigenic epitopes were selected and combined for further analysis. Multi-epitope peptides were constructed based on predicted MHC-I, MHC-II, and linear B-cell epitopes, yielding four promising candidates derived from C. acnes core proteins and IA1-specific proteins. Molecular docking analysis indicated that both groups showed binding affinity for TLR2 and TLR4 receptors, suggesting possible molecular compatibility with these receptors. Furthermore, in silico immune simulations indicated that both types of multi-epitope peptides were associated with simulated humoral and cellular immune response profiles, although these responses require experimental validation. This computational workflow may help narrow the selection of potential acne vaccine candidates and prioritise multi-epitope peptide constructs for subsequent vaccine design steps and experimental validation. Full article

Introduction: Streptococcus pneumoniae severely affects adults over 65, especially those with comorbidities. Since vaccination coverage among healthcare workers (HCWs) is unknown despite free availability, this study evaluates knowledge, behaviours, hesitancy and accessibility among employees of an Italian hospital. Methods: A prospective cross-sectional survey was administered via “SurveyMonkey.” From February 22 to June 15, 2024, healthcare and administrative staff aged ≥ 18 at the Fondazione Policlinico Universitario Gemelli were recruited by email. Descriptive and inferential analyses used Stata 16.1. Results: Among HCWs, 72% are women, with an average age of 48. Pneumococcal vaccination coverage is 20%, with 82.7% vaccinated in-hospital. Preferred information sources include courses, webinars, and institutional websites. For management staff, vaccine safety and effectiveness were significant determinants. Among administrative employees, 65% are women (average age 51); 19% are vaccinated, 24% are unsure, and 43% prefer in-hospital vaccination. Physicians cited trust in vaccines (25.3%) and self-protection (23.2%) as key motivators, compared with 12.4% among nursing, technical and rehabilitative staff. Recommendation to family members was higher among medical and specialist professionals (90%) than in other groups (77% in nursing/technical/rehabilitative; <50% in assistants and auxiliary staff). About half of the groups rated their knowledge at level 2 (scale 1–4). Multivariable regression analysis showed that medical professionals and specialists exhibited a higher perception of the importance and safety of vaccines compared with other categories. Conclusions: HCWs showed greater knowledge of pneumococcal vaccination, while administrative staff had lower awareness and more hesitancy. Both groups preferred in-hospital vaccination and expressed interest in structured educational initiatives. Full article

Background: Chagas disease, caused by Trypanosoma cruzi, remains a major public health problem in Latin America and an emerging concern worldwide. Current chemotherapies show limited efficacy during chronic infection, and no licensed vaccine is currently available. We previously developed the chimeric antigen N-Tc52/TSKb20 as a vaccine candidate against T. cruzi infection. In a murine model, this vaccine induced robust antigen-specific immune response associated with protection shortly after vaccination. Objectives: Here, we investigated the long-term persistence and effector functions of the immune responses elicited by this vaccine candidate. Methods: Both female and male C57BL/6 mice were immunized with three doses of N-Tc52/TSKb20 formulated with QuilA adjuvant. Serum samples collected 170 days post-immunization were analyzed for antigen-specific antibodies by ELISA and for trypanolytic activity against cell-derived trypomastigotes using an in vitro functional assay. Cellular immune responses were evaluated by measuring cytokine production, T cell activation, and memory T cell responses following in vitro re-stimulation with the vaccine antigen or T. cruzi antigens. Results: N-Tc52/TSKb20 vaccination induced a sustained antigen-specific humoral response, characterized by long-lasting IgG2c antibodies and functional activity persisting for up to 170 days post-immunization. In parallel, vaccination promoted long-term activation of antigen-specific CD8⁺ T cells and production of TNF-α and IFN-γ upon antigen re-encounter. A sex-dependent tendency was observed for IL-10, with increased production in vaccinated female mice. Moreover, vaccinated animals exhibited increased frequencies of central and effector memory CD4⁺ and CD8⁺ T cells in response to T. cruzi antigens, with a predominant contribution of CD8⁺ T cells, indicating the establishment of parasite-specific T cell memory. Conclusions: Together, these findings demonstrate that vaccination with N-Tc52/TSKb20 induces a long-lasting Th1-biased immune response characterized by trypanolytic antibodies, functional and durable T cell responses, and parasite-specific memory T cells. This immunological profile supports the potential of N-Tc52/TSKb20 as a promising vaccine candidate for Chagas disease and highlights its capacity to elicit immune mechanisms that have been associated with protection against T. cruzi infection. Full article

Leishmaniasis is a Neglected Tropical Disease caused by protozoa of the Leishmania genus. No human vaccine is available, and current treatments are limited by toxicity and drug resistance. Thus, the identification of new active molecules remains an urgent priority. However, drug discovery is severely hampered by the lack of fast, robust, and high-throughput screening assays, particularly for the clinically relevant intracellular amastigote stage. Here, a transgenic Leishmania infantum line stably co-expressing the bioluminescent marker PpyRE9H fused to the fluorescent reporter tdTomato was generated and used to develop a novel dual-reporter microplate-based platform to identify compounds active against promastigotes or intracellular parasite stages. The engineered strain exhibited comparable growth and infectivity to the wild-type strain, validating its suitability for drug screening assays. The activity of reference drugs was evaluated, and results were compared to those obtained using standard methods, such as MTT assay for promastigotes and Giemsa staining with microscopic quantification for amastigotes. Comparable IC₅₀ values were obtained using fluorescent/bioluminescent assays and conventional methods. These proposed assays provide a sensitive and reproducible alternative to conventional methods. The microplate format enables higher throughput screening, while the dual bioluminescence and fluorescence readouts enable cross-validation of results and reduce the risk of compound-specific signal interference. Full article

Background: Cervical cancer is among the most common cancers affecting women worldwide, with high morbidity and mortality in low- and middle-income countries. In Saudi Arabia, most cases are diagnosed at a late stage despite the availability of free HPV vaccination and screening. Objectives: To identify Saudi women’s perceptions of the HPV vaccine using the Health Belief Model, estimate willingness to receive the HPV vaccine and the factors influencing it, assess uptake of Pap smear and HPV vaccine, and define barriers to both practices. Methodology: A cross-sectional study of a convenience sample of 1334 Saudi women aged 16 to 65 years, from all regions of Saudi Arabia, was conducted. Data were collected via an online questionnaire that included sociodemographic characteristics, beliefs about the HPV vaccine based on the Health Belief Model, vaccine hesitancy, and HPV vaccine and Pap smear uptake. Data were analyzed using SPSS version 29. Results: Only 6% completed their vaccination series or received at least one dose; 37.3% planned to get vaccinated; and 56.7% stated they do not intend to get vaccinated. The main reasons for vaccine refusal were lack of trust (41.8%) and fear of side effects (32.3%). Only 21% had undergone Pap smear testing, with barriers including embarrassment and fear. Among the HBM constructs, perceived susceptibility, benefits, and barriers remained statistically significant predictors of HPV vaccination. Increased perceived susceptibility and benefits raise the likelihood of accepting the HPV vaccine, while higher perceived barriers lessen it. Vaccine hesitancy had a significant negative effect on willingness to receive the HPV vaccine (OR = 0.78, 95% CI 0.69–0.90, p < 0.01). Additionally, Pap smear uptake was an independent predictor of the intent to get the HPV vaccine (OR = 1.78, 95% CI 1.25–2.54, p < 0.01). The independent factors influencing HPV vaccine uptake were largely similar to those affecting the willingness to receive the vaccine, except for age, perceived benefits, and Pap smear uptake. Conclusions: There is a gap between Saudi women’s intention to get HPV vaccinated and actual vaccination. Women who saw a high risk of HPV-related cancer, believed in vaccine efficacy, had a Pap smear, and were open to vaccination were more likely to vaccinate. Hesitant women and those perceiving barriers were less likely to vaccinate or consider it. The main gaps for future campaigns are perceptions of HPV severity and cultural factors influencing decision-making. Emphasizing HPV as a cancer-related virus rather than a sexually transmitted infection can reduce barriers and highlight its severity. Full article

Bovine viral diarrhea (BVD) is a globally significant disease that adversely affects cattle health and productivity, including in India. It is caused by three bovine pestiviruses: bovine viral diarrhea virus 1 (BVDV-1), BVDV-2, and HoBi-like pestivirus (HoBiPeV), which belong to the Pestivirus genus within the Flaviviridae family. Despite the prevalence of all three pestivirus species in India, no commercial vaccine based on the local circulating strain is currently available. This study evaluates the safety, immunogenicity, and protective efficacy of an inactivated whole-virus BVD vaccine, based on an Indian BVDV-1 strain. The virus was propagated in MDBK cells, inactivated using 3 mM binary ethylenimine (BEI) for 24 h at 37 °C, and formulated with Montanide ISA 61 VG (SEPPIC) in a 50:50 water-in-oil emulsion. Vaccine safety was confirmed in both guinea pigs and bovine calves, with no adverse effects observed. Immunogenicity testing in guinea pigs (n = 6) showed neutralizing antibody titres up to 9 log₂ (1/512). In calves aged 9–12 months (n = 3), the vaccine elicited strong humoral and cell-mediated immune responses, with mean neutralizing antibody titres against the homologous BVDV-1 strain reaching 14 log₂ (1/16,384). Neutralizing antibody levels remained detectable for up to 12 months post vaccination with sustained mean titres of 7 log₂ (1/128). Notably, titres reported to be adequate for fetal protection (≥9 log₂ or ≥1/512 were maintained for five months following vaccination. Challenge studies demonstrated complete protection of vaccinated calves against homologous BVDV-1 acute infection. In addition, the vaccine conferred partial cross-protection against heterologous strains including BVDV-2 and HoBiPeV. In a field trial involving 125 cattle, 74% of animals developed protective neutralizing titres (≥7 log₂ or ≥1/128), while 48% achieved titres reported to be adequate for fetal protection (9 log₂ or 1/512). Furthermore, 92% of vaccinated cattle maintained neutralizing antibody titres of at least 6 log₂ (≥1/64) for up to six months post-booster vaccination. A strong positive correlation was observed between guinea pig and bovine antibody responses (R² = 0.6809; p < 0.0001), indicating the potential of guinea pigs as a predictive model. Vaccine stability was confirmed for up to 8 months when stored at 4 °C, as demonstrated by the immunogenicity in guinea pigs. Collectively, these findings demonstrate that the locally developed inactivated BVDV-1 vaccine is safe, highly immunogenic, and capable of providing protective immunity against BVDV-1 infection, supporting its potential use in BVD control programs in India. Full article

Background: Adenovirus-vectored vaccines played an important role in the global response to SARS-CoV-2. Adenovirus platforms have many advantages including a simple and readily transferred manufacturing process, low cost, and thermostability. Speed of production of an initial Good Manufacturing Practice (GMP)-compliant batch has, however, been viewed as a limitation of adenovirus vectors relative to mRNA platforms. Production of the initial viral starting material and release testing are key rate-limiting steps. Methods: Production of viral starting material from DNA, and release testing in accordance with regulatory expectations, for first-in-human trials of adenovirus-vectored vaccines. Results: We describe experience of these stages in the production of the first GMP batches for multiple adenovirus-vectored candidates and the adaptations made for ChAdOx1 nCoV-19 (the Oxford COVID-19 vaccine) in early 2020. We also report development of a streamlined approach to starting material generation, enabling initial GMP batch availability within c. 60 days of publication of a new pathogen sequence. Using a New World arenavirus vaccine construct as a proof of concept, we demonstrate reproducible execution of this pipeline, maintaining acceptable infectivity and other quality attributes. Conclusions: We discuss opportunities for additional time savings in the future. This work demonstrates suitability of an adenovirus platform to contribute to the “100 Days Mission” for vaccines against “Disease X”. Full article

Enterovirus B (EVB) is the most prevalent species of human enteroviruses, responsible for a wide range of diseases, including hand, foot, and mouth disease, viral meningitis, myocarditis, and neonatal sepsis, imposing a significant disease burden primarily on children. Coxsackievirus B (CVB1-6) and various echovirus (E) serotypes are the major serotypes of EVB. Since no antiviral drug or vaccine is available, it is important to strengthen monitoring, risk assessment, and early warning of genomic variations for EVB. CVB1, CVB3, E6, and E30 were selected as representative EVB serotypes for this study due to the availability of three-dimensional structures and their global prevalence. To evaluate the mutation effects of structural proteins on structural stability and receptor-binding affinity, computational saturation mutagenesis of EVB serotypes was performed using FoldX. Furthermore, based on data from deep mutational scanning for CVB3, a risk prediction model for EVB fitness was constructed by machine learning algorithms and applied to other EVB serotypes. Finally, we integrated three phenotypes—structural stability, receptor-binding affinity and fitness—to evaluate genomic variation risk of EVB and tracked the prevalence of high-risk mutants in natural viral sequences through molecular evolution analysis and mutation profiles. We identified the N-terminus and C-terminus of VP1 and the EF loop of VP2 as the EVB regions of highest genomic variation risk, and high-risk mutations had played significant roles in viral evolutionary history. These findings provide a framework for multi-phenotypic and multi-data approaches to viral risk assessment and offer insights to support the development of antiviral drugs and vaccines. Full article

Biologic and targeted synthetic therapies have substantially improved the management of autoimmune diseases (ADs), achieving unprecedented disease control. However, by modulating key immune pathways, these agents increase susceptibility to a wide spectrum of infections. This narrative review synthesizes current evidence on infectious risks associated with biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) in AD, characterizing infection profiles across different drug classes, identifying patient- and treatment-related risk factors, and providing evidence-based recommendations for screening, prevention, and management. A comprehensive literature search was conducted through March 2026, across PubMed, Embase, and the Cochrane Library, using predefined search terms combining biologic and targeted synthetic drug classes with infection-related outcomes. Evidence from major international registries (BSRBR-RA, DANBIO, RABBIT) and society guidelines (ACR, EULAR, IDSA) was prioritized. Among bDMARDs, TNF-α inhibitors (TNF-α i) and rituximab were associated with the highest rates of serious infections, whereas IL-17 and IL-23 inhibitors demonstrated comparatively lower infectious risk profiles. Steroids, older age, and prior serious infections emerged as the most consistent patient-related risk modifiers. Unlike prior reviews focused on single diseases or drug classes, this work provides an integrated, cross-disciplinary risk stratification framework. bDMARDs and tsDMARDs remain among the most innovative treatments available for effective management of ADs, with favorable benefit–risk profiles when accompanied by systematic prevention strategies. Universal pre-treatment screening for tuberculosis and viral hepatitis, risk-stratified parasitic screening, evidence-based vaccination, and selective antimicrobial prophylaxis can mitigate infectious complications. Full article

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