Search Results (3,046)

Background: Poxviruses constitute a family of large dsDNA viruses that can infect a plethora of species including humans. Historically, poxviruses have caused a health burden in multiple outbreaks. The large genome of poxviruses favors reverse vaccinology approaches that can determine potential antigens and epitopes. Here, we propose the modeling of a user-friendly database containing the predicted antigens and epitopes of a large cohort of poxvirus proteomes using the existing PoxiPred method for reverse vaccinology of poxviruses. Methods: In the present study, we obtained the whole proteomes of as many as 37 distinct poxviruses. We utilized each proteome to predict both antigenic proteins and T-cell epitopes of poxviruses with the aid of an Artificial Intelligence method, namely the PoxiPred method. Results: In total, we predicted 3966 proteins as potential antigen targets. Of note, we considered that this protein may exist in a set of proteoforms. Subsets of these proteins constituted a comprehensive repository of 54,291 linear T-cell epitopes. We combined the outcome of the predictions in the format of a web tool that delivers a database of antigens and epitopes of poxviruses. We also developed a comprehensive repository dedicated to providing access to end-users to obtain AI-based screened antigens and T-cell epitopes of poxviruses in a user-friendly manner. These antigens and epitopes can be utilized to design experiments for the development of effective vaccines against a plethora of poxviruses. Conclusions: The TCEPVDB repository, already deployed to the web under an open-source coding philosophy, is free to use, does not require any login, does not store any information from its users. Full article

Background/Objectives: Vaccination is a critical public health measure for older adults in residential aged care facilities (RACFs). In Australia, COVID-19, influenza, pneumococcal, and shingles vaccines are recommended and funded for this group. However, vaccination coverage remains suboptimal, with limited understanding of the underlying causes. Methods: A mixed-methods design explored the enablers and barriers to vaccination from the perspectives of frontline providers, RACF staff, residents and family members. Descriptive statistics were used to quantify the prevalence of perceived enablers and barriers within stakeholder groups. Qualitative data—collected through open-ended questions—were analysed using manual, deductive-iterative coding to identify key themes. Key quotes illustrate the findings. Results: Input was gathered from seven in-reach geriatric staff, 40 general practitioners (GPs), 90 RACF staff, 17 RACF residents, and 84 family members of residents. Results were grouped under four key themes: operational, communication, coordination, and financial. RACF staff identified limited access to vaccination histories as the most significant barrier and relied on external providers to upload data to the Australian Immunisation Register (AIR). On-site clinics were essential, but organisational policies prevented nurse-led vaccination of residents. Most RACFs stored only influenza vaccines and depended on external providers for others. Simplified, translated information was called for. Healthcare provider and RACF endorsement was valued, but RACF staff felt ill-equipped to handle conversations around vaccine hesitancy. Consent processes were burdensome, and responsibility for tracking vaccination schedules was unclear with calls for streamlined processes. Low provider remuneration was also noted, with calls for increased government support. Conclusions: This work identifies key enablers and barriers to resident vaccination in RACFs. Improving delivery requires organisational policy change, staff support, digital access, and continued advocacy. Analysis of targeted interventions and coverage will be reported separately. The approach is replicable for other vulnerable groups. Full article

The Transdermal Drug Delivery System (TDDS) offers several benefits, such as enhanced patient adherence, controlled release, reduced gastric irritation, and the bypassing of the first-pass metabolism. However, not all drugs can be delivered through this route in effective doses. Biodegradable microneedles (BMn) are designed to improve TDDS. This review outlines various types of BMn and their fabrication methods. BMn are produced in different forms, including hollow, solid, dissolve, and hydrogel-forming versions, which have garnered significant attention. These innovative BMn do not contain drugs themselves but instead absorb interstitial fluid to create continuous channels between the dermal microcirculation and a drug-containing patch. Several types of BMn have been tested and approved by regulatory bodies. The use of BMn technology is rapidly growing in point-of-care applications, attracting significant interest from both researchers and healthcare providers. BMn-based Point-of-care (POC) devices have high efficacy for finding various analytes of clinical interests and transdermal drug administration in a minimally invasive manner owing to BMn’ micro-size sharp tips and ease of use. Porous BMn technology may have a very rising future in the case of a vaccine delivery system. Full article

Background: Respiratory syncytial virus (RSV) is a major pathogen of acute lower respiratory tract infection (LRTI) in infants, the elderly, and immunocompromised individuals. This review focuses on the progress of RSV vaccine development, especially subunit vaccines targeting the fusion protein (F) and attachment glycoprotein (G), aiming to summarize key strategies, challenges, and future directions in the field. Methods: The review is based on a comprehensive literature search and analysis of recent studies on RSV vaccine development, with a specific focus on subunit vaccines and related technologies. Results: Approved vaccines such as Abrysvo and Arexvy utilize structural engineering to stabilize the prefusion conformation of the F protein (PreF), thereby exposing neutralizing epitopes. Subunit vaccine candidates such as DS-Cav1 and DT-PreF enhance stability through disulfide bonds and dityrosine linkages, while ADV110 targets the conserved domain of the G protein to elicit cross-strain immunity. Virus-like particle (VLP) vaccines like IVX-A12 combine RSV and human metapneumovirus antigens to provide broad-spectrum immunity. However, challenges exist, including maintaining PreF stability, overcoming immunosenescence in the elderly, and addressing safety concerns like Guillain-Barré syndrome (GBS). Conclusions: Future RSV vaccine development should center on combined PreF-G protein vaccines, VLP technology, and optimizing cold-chain logistics to improve global accessibility and overcome existing challenges, thereby providing more effective prevention and control of RSV infections. Full article

Senecavirus A (SVA) causes a vesicular disease in pigs with clinical signs indistinguishable from those of other swine vesicular diseases. To enable serological differentiation infected from vaccinated animals (DIVA), we developed indirect ELISAs (iELISAs) based on recombinant non-structural proteins (NSPs). A His-tagged tandem antigen, r3AB-3C, was designed by integrating immunodominant B-cell epitopes from 3AB and 3C proteins, and was successfully expressed in Escherichia coli (E. coli) and purified alongside the individual r3AB and r3C proteins. Serological evaluation results showed that the immunoreactivity of the r3AB-3C iELISA was superior to that of r3AB, which in turn was better than r3C. The r3AB-3C and r3AB iELISAs were subsequently validated. The cut-off values were established at sample-to-positive (S/P) ratios of ≥0.2635 for the r3AB-3C iELISA and ≥0.5775 for the r3AB iELISA. The r3AB-3C iELISA demonstrated higher sensitivity for detecting infection-induced antibodies than the r3AB iELISA, despite the later seroconversion of anti-NSP antibodies compared to neutralizing antibodies. In a serosurvey, the r3AB-3C iELISA revealed seropositivity rates of 35.2% in 2023 and 22.3% in 2024. In conclusion, the r3AB-3C iELISA is a valuable serological tool for monitoring SVA infection, effectively supporting DIVA strategies. Full article

The ongoing evolution of SARS-CoV-2 has given rise to variants with enhanced transmissibility and pathogenicity, many of which harbor mutations in the receptor-binding domain (RBD) of the viral spike protein. These mutations often confer increased viral fitness and immune evasion by modulating interactions with the human ACE2 receptor (hACE2) and escaping neutralizing antibodies. Accurate prediction of the functional consequences of such mutations—particularly their effects on receptor binding and antibody escape—is critical for assessing the public health threat posed by emerging variants. In this study, we apply a Mutation-dependent Biomacromolecular Quantitative Structure–Activity Relationship (MB-QSAR) framework to quantitatively model the biochemical phenotypes of RBD variants. Trained on comprehensive deep mutational scanning (DMS) datasets, our models exhibit strong predictive performance, achieving correlation coefficients (r²) exceeding 0.8 for hACE2 binding affinity and 0.7 for antibody neutralization escape. Importantly, the MB-QSAR approach generalizes well to multi-mutant variants and currently circulating lineages. Structural analysis based on model-derived interaction profiles offers mechanistic insights into key RBD–ACE2 and RBD–antibody interfaces, helping the rational design of broadly protective vaccines and therapeutics. This work establishes MB-QSAR as a rapid, accurate, and interpretable tool for the prediction of protein–protein interaction and forecasting viral adaptation, thereby facilitating early risk assessment of novel SARS-CoV-2 variants. Full article

Dengue virus remains a major global health threat due to the lack of a safe and broadly effective vaccine. Traditional antibody-based vaccines often show limited protection and can exacerbate disease severity in individuals without prior exposure. A new generation of T-cell epitope-based vaccines offers a promising and safer approach by activating the cellular arm of the immune system to complement antibody responses. Instead of targeting only surface structural proteins, these vaccines focus on highly conserved peptide regions within non-structural proteins, particularly NS3 and NS5, that are shared across all four dengue virus serotypes. Peptides such as DTTPFGQQR, KPGTSGSPI, and MYFHRRDLRL have been identified as potent immunogenic targets capable of inducing strong cytotoxic and helper T-cell responses, promoting viral clearance and long-term immune memory. Advanced immunoinformatic enables precise prediction and selection of epitopes with high binding affinity to human leukocyte antigens and broad cross-serotype conservation. These peptides can be integrated into next-generation vaccine delivery systems, including messenger RNA and nanoparticle platforms, which enhance antigen presentation, improve molecular stability, and reduce the risk of antibody-dependent disease enhancement. Together, this integrative design represents a rational path toward a safer, cross-protective, and durable dengue vaccine that closely mimics the balanced cellular and humoral immunity observed after natural infection, offering renewed hope for effective global dengue prevention. Full article

Background/Objectives: Varicellovirus bovinealpha1 and Varicellovirus bovinealpha5 (BoAHV-1 and BoAHV-5), respectively, are widely distributed pathogens that cause distinct clinical conditions in cattle including infectious bovine rhinotracheitis, infectious pustular vulvovaginitis/balanoposthitis, and meningoencephalitis. Due to the establishment of viral latency, controlling these infections is challenging, and vaccination remains the most effective strategy. In this study, vaccine candidates targeting both BoAHV-1 and BoAHV-5 were developed. Methods: A synthetic gene encoding immunodominant epitopes from the gB and gD proteins and tegument phosphoprotein of BoAHV-1 and BoAHV-5 was designed to produce a multi-epitope recombinant antigen, expressed both in a prokaryotic system (RecBoAHV) and by a modified vaccinia Ankara (MVA-BoAHV) viral vector. The binding affinity of MHC-I to bovine leukocyte antigens (BoLA) was predicted using the NetMHCpan tool (version 4.1). The immunogenicity of the vaccine candidates was evaluated in rabbit and mouse models, using prime-boost immunization protocols. Sera from bovines naturally infected with BoAHV-1 and/or BoAHV-5 were used to evaluate the chimeric protein antigenicity. Immune responses were assessed by indirect ELISA and Western blot. Results: The recombinant multi-epitope protein was effectively recognized by IgG and IgM antibodies in sera from cattle naturally infected with BoAHV-1 or BoAHV-5, confirming the antigenic specificity. Both RecBoAHV and MVA-RecBoAHV induced strong and specific humoral immune responses in rabbits following a homologous prime-boost regimen. In mice, both homologous and heterologous prime-boost protocols revealed robust immunogenicity, particularly after the second booster dose. Conclusions: These findings highlight the immunogenic potential of the RecBoAHV multi-epitope vaccine candidates for controlling BoAHV-1 and BoAHV-5 infections. Further characterization of these vaccine formulations is currently underway in bovine, the target specie. Full article

Background: Tuberculosis (TB) constitutes one of the leading causes of morbidity and mortality worldwide. Due to adopted prevention measures, good public health practices, and better treatment, its incidence, prevalence, and case fatality rates steadily fell. Objectives and Methods: Following a case–control research design, this study aimed to explore the risk factors of pulmonary TB among patients registered in the Aseer Region, Saudi Arabia. This study included 105 active TB cases (study group) and 143 (control group) who were randomly recruited from those attending the vaccination units at Primary Healthcare Centers in Aseer. Results: Participants differed significantly according to their nationality (with 65.7% being Saudi in the TB group compared with 89.5% Saudi nationals in the control, p < 0.001); educational status (with 27.6% being university graduates in the TB group compared with 53.8% in the control, p < 0.001); marital status, with most TB patients being single, compared with control (70.5%, and 44.1%, p < 0.001); monthly income, with lower income <5000 Saudi Riyals (SRs), among TB patients than control subjects (80% and 44.1%, p < 0.001); and body mass index (20% of the TB patients were underweight, compared with 6.3% in the control, p < 0.001). Also, participants differed significantly according to their residence, with more rural residence among TB patients than control (18.1% and 7%, p = 0.007), and type of houses, with 84.8% of TB patients living in apartments, compared to 68.5% of the control (p < 0.001). The binary logistic regression model of the possible risk factors related to pulmonary TB revealed that nationality, residence, and body mass index were the only significant independent risk factors (p < 0.001, p = 0.007, and p < 0.001). Conclusions: Personal characteristics of pulmonary TB patients include being non-Saudi, less educated, not married, unemployed, with a low monthly income, and being underweight. Risk factors related to place included residing in rural areas and living in the basement of a rented apartment. Full article

Digital twins (DTs), virtual replicas that integrate mechanistic modeling with real-time clinical data, are emerging as powerful tools in healthcare with particular promise in pediatrics, where age-dependent physiology and ethical considerations complicate infectious disease management. This narrative review examines current and potential applications of DTs across antimicrobial stewardship (AMS), diagnostics, vaccine personalization, respiratory support, and system-level preparedness. Evidence indicates that DTs can optimize antimicrobial therapy by simulating pharmacokinetics and pharmacodynamics to support individualized dosing, enable Bayesian therapeutic drug monitoring, and facilitate timely de-escalation. They also help guide intravenous-to-oral switches and treatment durations by integrating host-response markers and microbiological data, reducing unnecessary antibiotic exposure. Diagnostic applications include simulating host–pathogen interactions to improve accuracy, forecasting clinical deterioration to aid in early sepsis recognition, and differentiating between viral and bacterial illness. Immune DTs hold potential for tailoring vaccination schedules and prophylaxis to a child’s unique immune profile, while hospital- and system-level DTs can simulate outbreaks, optimize patient flow, and strengthen surge preparedness. Despite these advances, implementation in routine pediatric care remains limited by challenges such as scarce pediatric datasets, fragmented data infrastructures, complex developmental physiology, ethical concerns, and uncertain regulatory frameworks. Addressing these barriers will require prospective validation, interoperable data systems, and equitable design to ensure fairness and inclusivity. If developed responsibly, DTs could redefine pediatric infectious disease management by shifting practice from reactive and population-based toward proactive, predictive, and personalized care, ultimately improving outcomes while supporting AMS and health system resilience. Full article

Background/Objectives: To address vaccine hesitancy, health promotion strategies must go beyond passive information delivery and identify individuals’ beliefs about vaccination. Focus groups (FGs) have emerged as promising tools in health education and behavioral change initiatives. Methods: To assess the employ of FGs in planning immunization strategies for adolescents, a systematic review of literature was performed from inception to July 2025 following PRISMA guidelines. PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar databases were searched. Conclusions: Twenty articles met the inclusion criteria. In these studies, FGs were used to identify barriers or facilitators to vaccination, mainly to address HPV vaccine hesitancy. Across the WHO SAGE 3C framework, the outcomes of FGs clustered more in confidence and convenience/constraints than in complacency domain. These findings highlight the potential of FGs in designing programs to increase vaccine uptake. Further research on their possible role in motivating parents or adolescents towards immunization is needed. Full article

Invasive group A streptococcal (iGAS) infections are increasingly recognized as a global public health concern, with a notable resurgence observed among pediatric populations in high-income countries following the relaxation of COVID-19-related restrictions. While the most commonly implicated emm types in invasive disease are emm1 and emm3, the global distribution of Streptococcus pyogenes strains is highly diverse, posing challenges for surveillance and vaccine development. We describe a 3-year-old boy with a femoral subperiosteal abscess, a rare clinical manifestation of iGAS, caused by an emm6.10 S. pyogenes strain. The diagnosis was confirmed by positive blood cultures and magnetic resonance imaging. Antibiotic therapy included intravenous ceftriaxone followed by oral amoxicillin, and then prolonged oral clindamycin was introduced due to the deep-seated nature of the infection. Molecular typing was performed by the national reference center as part of routine surveillance of invasive strains. This case emphasizes the importance of recognizing atypical clinical presentations of iGAS in children and the crucial role of strain typing in epidemiological monitoring. It also illustrates how the remarkable emm-type diversity of S. pyogenes remains a major obstacle to effective vaccine design, despite ongoing efforts with multivalent M-protein-based candidates and alternative strategies targeting conserved antigens. Enhanced global surveillance and inclusive vaccine design are urgently needed to address the full spectrum of circulating GAS strains. Full article

Background/Objectives: The Dutch National Immunisation Programme (NIP) aims to protect children against severe infectious diseases. As with all vaccines, adverse events following immunisation (AEFIs) may occur with the use of vaccines in the NIP. Safety of the vaccines is monitored by The Netherlands Pharmacovigilance Centre Lareb. This study aimed to systematically document AEFIs following administration of the MMR and DT-IPV vaccines, which are given simultaneously at the age of 9 years. Methods: A cohort event monitoring (CEM) study was performed, employing a longitudinal cohort design. Parents or guardians of 9-year-olds receiving the MMR and DT-IPV vaccines completed questionnaires following vaccination to report the presence or absence of AEFI. Results: AEFIs were reported for more than 73% of children given an MMR and DT-IPV vaccination. The great majority of the reported reactions were non-serious and self-limiting and consistent with those listed in the official product information for the MMR and DT-IPV vaccines. Injection site reactions were significantly more frequent at the site of the DT-IPV vaccination than the MMR vaccination. AEFIs were mostly perceived as little or moderately burdensome. Conclusions: AEFIs very frequently occurred after MMR and DT-IPV vaccination. This study provides further insight into the timing and duration of AEFIs after MMR and DT-IPV vaccination. In addition, detailed insight into the adverse event profile of these vaccines is provided, which helps to set realistic expectations for children and their parents or caretakers who follow the NIP and helps health professionals in their communication regarding AEFIs. Full article

Background: In response to the emergence of immune-evasive variants of SARS-CoV-2, this study explores a novel heterologous vaccination strategy using a microparticulate formulation approach that is delivered via oral dissolving film (ODF) formulations into the buccal cavity. Heterologous administration has the potential to generate cross-reactive antibodies, which can be especially beneficial against viruses with ever-mutating variants. Moreover, the microparticulate oral dissolving film-based vaccine approach is a non-invasive vaccine delivery platform. Methods: The vaccine design incorporated whole inactivated Delta and Omicron variants of the virus, administered at prime and booster doses, respectively, effectively encapsulated in a Poly(lactic-co-glycolic) acid (PLGA) polymer matrix, and adjuvanted with Alum to enhance immune activation. Following vaccination, serum, mucosal, and tissue samples were analyzed to evaluate humoral and cellular immune responses against the model antigen, as well as other variants such as Alpha and Beta variants, to understand the cross-reactive response. Result: In vitro evaluations confirmed the vaccine’s safety and its ability to stimulate immune responses. On administering microparticulate oral dissolving films to mice, whole inactivated delta and omicron variant-specific antibodies were observed in serum samples along with neutralizing titers in terminal week. The formulated vaccine showed significant secretory IgA antibody levels in mucosal samples. Moreover, CD4⁺ and CD8a cellular responses were observed in tissue samples of spleen and lymph nodes, along with antibodies (IgG, IgA, and IgM) detected in lung supernatant samples. Humoral and cellular cross-reactive antibodies were observed in the samples. Conclusions: This approach offers a promising platform for developing next-generation vaccines capable of inducing broad immunity. Full article

Background: Mammalian orthoreovirus is a ubiquitous double-stranded RNA virus that causes mild respiratory and enteric infections, primarily in infants and young children. Its significant environmental stability and association with conditions like celiac disease highlight an unmet medical need, as no licensed vaccine or antiviral treatment currently exist. Methods: An immunoinformatics-driven approach was employed to design a multi-epitope vaccine. The highly antigenic inner capsid protein Sigma-2 was used to predict cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and linear B cell epitopes using NetCTL, NetMHCpan, NetMHCIIpan, and IEDB tools. Selected epitopes were fused with appropriate linkers. The construct’s antigenicity, allergenicity, and physicochemical properties were evaluated. The tertiary structure was predicted with AlphaFold2, refined, and validated. Molecular docking with TLR2 and TLR4 was performed using HDOCK, and immune response simulation was conducted with C-ImmSim. Finally, the sequence was codon-optimized for E. coli expression using JCat. Results: The final vaccine construct comprises one CTL, four HTLs, and one B cell epitope. It is antigenic (VaxiJen score: 0.5026), non-allergenic, and non-toxic and possesses favorable physicochemical properties, including stability (instability index: 32.28). Molecular docking revealed exceptionally strong binding to key immune receptors, particularly TLR2 (docking score: −324.37 kcal/mol). Immune simulations predicted robust antibody production (elevated IgM, IgG1, and IgG2) and lasting memory cell formation. Codon optimization yielded an ideal CAI value of 0.952 and a GC content of 57.15%, confirming high potential for recombinant expression. Conclusions: This study presents a novel multi-epitope vaccine candidate against reovirus, designed to elicit broad cellular and humoral immunity. Comprehensive in silico analyses confirm its structural stability, potent interaction with innate immune receptors, and high potential for expression. These findings provide a strong rationale for further wet-lab studies to validate its efficacy and advance it as a promising prophylactic candidate. Full article