Search Results (1,004)

Cancer immunotherapy increasingly relies on nucleic acid-based vaccines, yet achieving efficient and safe delivery remains a critical limitation. Polyplexes—electrostatic complexes of cationic polymers and nucleic acids—have emerged as versatile carriers offering greater chemical tunability and multivalent targeting capacity compared to lipid nanoparticles, with lower immunogenicity than viral vectors. This review summarizes key design principles governing polyplex performance, including polymer chemistry, architecture, and assembly route—emphasizing microfluidic fabrication for improved size control and reproducibility. Mechanistically, effective systems support stepwise delivery: tumor targeting, cellular uptake, endosomal escape (via proton-sponge, membrane fusion, or photochemical disruption), and compartment-specific cargo release. We discuss therapeutic applications spanning plasmid DNA, siRNA, miRNA, mRNA, and CRISPR-based editing, highlighting preclinical data across multiple tumor types and early clinical evidence of on-target knockdown in human cancers. Particular attention is given to physiological barriers and engineering strategies—including size-switching systems, charge-reversal polymers, and tumor-penetrating peptides—that improve intratumoral distribution. However, significant challenges persist, including cationic toxicity, protein corona formation, manufacturing variability, and limited clinical responses to date. Current evidence supports polyplexes as a modular platform complementary to lipid nanoparticles in selected oncology indications, though realizing this potential requires continued optimization alongside rigorous translational development. Full article

Outcomes of influenza virus infection vary widely across individuals, reflecting not only viral genetics and host factors but also the composition and function of the airway microbiome. Over the past few years, mechanistic work has clarified how specific commensals (for example, Staphylococcus epidermidis and Streptococcus oralis) restrict influenza replication by priming epithelial interferon-λ programs, reshaping intracellular metabolite pools (notably polyamines), dampening host protease activity, and maintaining barrier integrity; meanwhile, pathobionts (notably Staphylococcus aureus and Streptococcus pneumoniae) can enhance viral fitness via secreted proteases and neuraminidases that activate hemagglutinin and remodel sialylated glycoconjugates and mucus, setting the stage for secondary bacterial disease. Recent studies also highlight the gut–lung axis: gut microbiota-derived short-chain fatty acids (SCFAs), especially acetate, protect tight junctions and modulate antiviral immunity in influenza models. Together, these insights motivate translational strategies—from intranasal live biotherapeutics (LBPs) to metabolite sprays and decoy/dual neuraminidase approaches—that complement vaccines and antivirals. We synthesize recent evidence and outline a framework for leveraging the airway microbiome to prevent infection, blunt severity, and reduce transmission. Key priorities include strain-level resolution of commensal effects, timing/dosing windows for metabolites and LBPs, and microbiome-aware clinical pathways for anticipating and averting bacterial coinfection. Overall, the airway microbiome emerges as a tractable lever for influenza control at the site of viral entry, with several candidates moving toward clinical testing. Full article

Background: Cervical cancer is associated with Human Papillomavirus (HPV) infection. Besides cervical cancer, oro-pharyngo-laryngeal or uro-genital cancers are also reported. The HPV vaccine has been strongly recommended for school age children. However, the parents’ or guardians’ hesitancy remains. Methods: This is a mixed-method study in which the parents or guardians of school children, aged 10–18 years, were enrolled voluntarily. Their general demographic data, knowledge, attitudes, and awareness of vaccine accessibility, healthcare cost entitlement of the children, types of school affiliation, education administration areas where the schools were located, and the presence of a healthcare professional in family were analyzed by multiple logistic regression analysis adjusted with all studied variables to define the significant associated factors with the parents’ or guardians’ HPV vaccine acceptance (p < 0.05). In-depth interviews were subsequently performed with the selected participants until the qualitative data were saturated. Thematic analysis was applied, and the results of the two study methods were integrated to explore the reasons for vaccine acceptance or hesitancy. Results: A total of 943 questionnaire respondents were enrolled, among whom 75.8% were female and 86.4% were parents. A total of 663 (70.3%) participants accepted the HPV vaccine. Parents’ or guardians’ knowledge and attitudes, awareness of vaccine accessibility, type of school affiliation, the children’s healthcare cost entitlement, and the presence of a healthcare professional in the family were significantly associated with vaccine acceptance in the multivariate analysis (p < 0.05). The qualitative study revealed that misunderstanding of the vaccine’s safety and benefits combined with inadequate reliable information sources were associated factors with HPV vaccine hesitancy among the parents or guardians. Conclusions: Providing clear-cut knowledge about the HPV vaccine benefit vs. risk and clearing financial barriers for the parents or guardians of school children are advocated. Full article

Background: Women’s empowerment has been significantly associated with improved child health outcomes. Cambodia, amid a rapid socioeconomic transition, offers a critical setting to examine how advancements in women’s empowerment over the past decade have influenced child immunization completion within the first two years of life. Methods: Data from the Cambodia Demographic and Health Surveys conducted in 2010, 2014, and 2021–22, encompassing 9222 women with recent births, were analyzed. Empowerment was measured across literacy and information access, employment, and decision-making domains. Multinomial logistic regression assessed associations between empowerment factors and completion of oral polio (OPV), diphtheria–tetanus–pertussis (DTP), pneumococcal conjugate (PCV), and measles–rubella (MR) vaccines, adjusting for demographic and socioeconomic variables. Results: Between 2010 and 2022, women’s empowerment in Cambodia improved significantly, marked by higher literacy rates, nearly half of women completing primary education, and expanded digital access, with 82.4% owning mobile phones and approximately 50% using the internet daily. While non-working women slightly increased, agricultural employment declined by 20%, and cash earnings rose from 48.7% to 82.5%. Most women participated in major household decision-making, either independently or jointly. Completion rates for OPV, DTP, and PCV ranged from 79% to 83%, while just over half of children were fully vaccinated against measles. Higher maternal education and cash earnings were positively associated with OPV, DTP, and PCV completion but negatively associated with measles vaccination. Women in agricultural work were less likely to complete measles vaccination for their children than non-working women. Joint decision-making regarding the use of respondents’ income was associated with a higher likelihood of measles non-completion (OR = 2.26, 95% CI: 1.13–4.51), whereas joint decision-making about respondents’ health care was associated with a higher likelihood of measles completion (OR = 0.42, 95% CI: 0.21–0.83). Conclusions: Women’s empowerment remains a key determinant of vaccination outcomes in Cambodia. The distinct pattern observed for measles suggests that vaccines scheduled for older ages encounter greater structural and behavioral barriers. To overcome these challenges, strategies should focus on enhancing defaulter tracking, implementing reminder systems, expanding outreach and catch-up programs, and improving the convenience of vaccination services. Full article

Background: Vaccinations are essential to protect travelers from infectious diseases, especially in high-risk destinations. However, awareness and adherence to vaccination recommendations vary, influenced by communication, personal beliefs, and behavior. Methods: A focus group was conducted in February 2025 at a local health authority in central Italy, specifically within its travel clinic, to explore travelers’ awareness, attitudes, and behaviors regarding vaccination. The discussion was analyzed using the “3Cs” Vaccine Hesitancy model. Participants were purposively selected to ensure diversity and representativeness. Discussions included past travel experiences, knowledge of required vaccines, motivations for immunization, and barriers to access. Results: Four key thematic areas emerged: socio-cultural/environmental factors, psychological/emotional influences, knowledge/information access, and general health perceptions. Communication gaps often weakened belief in vaccine efficacy and necessity. Cultural background, past experiences, and risk perception heavily influenced decisions. Discussion: Although vaccination is widely viewed as a protective measure, vaccine hesitancy persists due to misinformation and limited institutional trust. The COVID-19 pandemic intensified both awareness and skepticism. The 3Cs model clarified hesitancy levels and barriers, emphasizing the need for effective communication and trust-building. Conclusions: Enhancing access to accurate information, strengthening healthcare professionals’ communicative role, and reducing economic obstacles are crucial. Tailored awareness campaigns and integrated health policies are essential to increasing vaccine uptake, safeguarding traveler health, and limiting global disease spread. Patient or Public Contribution: Members of the public contributed to this study by participating in a focus group, where they shared their personal experiences, perceptions, and opinions regarding travel-related vaccinations. Their insights provided valuable qualitative data that helped inform the study’s findings. However, they were not involved in the study design, the analysis of the data, or the preparation of the manuscript. The role of participants was limited to the data collection phase of the study. Full article

Emerging and re-emerging viruses continue to pose major threats to public health. Their ability to adapt, cross species barriers, and spread rapidly can trigger severe outbreaks or even pandemics. Strengthening preparedness with comprehensive and efficient strategies is therefore essential. Here, we explore the key components of viral outbreak preparedness, including surveillance systems, diagnostic capacity, prevention and control measures, non-pharmaceutical interventions, antiviral therapeutics, and research and development. We emphasize the increasing importance of genomic surveillance, wastewater-based surveillance, real-time data sharing, and the One Health approach to better anticipate zoonotic spillovers. Current challenges and future directions are also discussed. Effective preparedness requires transparent risk communication and equitable access to diagnostics, vaccines, and therapeutics. The COVID-19 pandemic highlighted both the promise of next-generation vaccine platforms and the necessity of maintaining diagnostic capacity, as early testing delays hindered containment efforts. Countries adopted various non-pharmaceutical interventions: risk communication and social distancing proved to be the most effective, while combined workplace infection-prevention measures outperformed single strategies. These experiences highlight the importance of early detection, rapid response, and multisectoral collaboration in mitigating the impact of viral outbreaks. By applying best practices and lessons learned from recent events, global health systems can strengthen resilience and improve readiness for future viral threats. Full article

Cancer is one of the biggest health burdens for women in the Middle East and North Africa (MENA), with the incidence of breast, cervical and colorectal cancer on the rise. Although preventive measures such as the HPV vaccination and population-based screening are available, access to them remains very unequal. Women in rural, low-income and refugee communities face additional barriers, cultural stigmatisation, low health literacy, gender norms and fragile health systems, leading to delayed diagnoses and poorer outcomes. This review summarises the results of 724 peer-reviewed publications to assess the current situation of cancer screening in MENA and Mediterranean countries. The studies were classified into four dimensions: cancer type (breast, cervical, colorectal), behavioural constructs (awareness, uptake, education), vulnerability factors (e.g., migrants, refugees, low-literacy groups), and geography (indigenous MENA populations versus diaspora and Mediterranean immigrant communities). The results show large inequalities in access and participation due to fragmented policies, socio-cultural resistance and infrastructure gaps. Nevertheless, promising approaches are emerging: community-led outreach, mobile screening programmes, AI-assisted triage and culturally appropriate digital health interventions. Comparisons between the local and diaspora populations make it clear that systemic and cultural barriers persist even in well-equipped facilities. Closing the screening gap requires a culturally sensitive, digitally enabled and policy aligned approach. Key priorities include engaging religious and community leaders, promoting men’s engagement in women’s health and securing sustainable funding. With coordinated action across all sectors, MENA countries can build inclusive screening programmes that reach vulnerable women and reduce preventable cancer mortality. Full article

Therapeutic peptides have rapidly evolved into multifunctional tools for precision oncology, offering molecular specificity and biocompatibility. Their roles in cancer therapy, however, are inherently overlapping. The same peptide can function as a targeting ligand, a cell-penetrating motif, a therapeutic effector, or a structural component of peptide–drug conjugates (PDCs), nanoparticle (NP) systems, and radionuclide constructs. This functional convergence makes rigid classification challenging. In this review, we therefore organize peptide modalities according to their dominant therapeutic function while acknowledging the fluid boundaries between categories. Firstly, we outline the main functional classes of therapeutic peptides, covering their use as targeting ligands and their roles as active agents (i.e., receptor agonists/antagonists, intracellular protein–protein interaction modulators, etc.). Additionally, we summarize their application in peptide–drug conjugates (PDCs), peptide-guided radionuclides, and cancer vaccines, integrating key mechanistic principles and clinical evidence. Finally, we discuss the major translational barriers to clinical use and how they might be overcome. The developments in peptide engineering position them as adaptable, multifunctional platforms capable of improving precision, reducing toxicity, and advancing personalized cancer care. Full article

Influenza and other respiratory viruses pose significant public health threats among SARI patients, yet comprehensive surveillance data remain limited in Pakistan. This prospective, multi-center study characterized the burden, distribution, and molecular evolution of respiratory viruses among hospitalized SARI patients across seven tertiary hospitals from November 2022 to June 2025. Specimens were tested using RT-PCR for influenza, SARS-CoV-2, and RSV, with 375 samples sequenced via Oxford Nanopore Technology. Among 11,451 specimens, 2818 (24.6%) tested positive: RSV (1648, 14.4%), influenza (855, 7.5%; 45% H1N1pdm09, 35% H3N2, 20% influenza B), and SARS-CoV-2 (315, 2.8%). RSV predominantly affected children under 2 years (63%), while influenza and SARS-CoV-2 primarily impacted adults aged 15–40 years. Male predominance (65–79%) reflected healthcare access barriers. Strong winter seasonality (December–February) was observed for influenza and RSV. ICU admission rates were 17% for influenza, 16% for RSV, and 4% for SARS-CoV-2. Shortness of breath was associated with influenza (OR = 1.62) and RSV (OR = 1.27), while malaise (OR = 2.24) and myalgia (OR = 3.87) was associated with SARS-CoV-2. Phylogenetic analysis revealed vaccine-matched influenza clades and rapid SARS-CoV-2 variant succession (3–4 months). RSV is the primary SARI pathogen in young children, necessitating maternal vaccines and nirsevimab implementation. Sustained genomic surveillance remains essential for pandemic preparedness. Full article

Celiac disease (CeD) is a chronic, immune-mediated enteropathy triggered by dietary gluten in genetically susceptible individuals, with environmental and epigenetic factors also contributing to its pathogenesis. Once considered a rare pediatric malabsorptive disorder, CeD is now recognized as a systemic condition that can manifest with both gastrointestinal and extraintestinal symptoms across the lifespan. Although strict adherence to a gluten-free diet (GFD) remains the cornerstone of treatment, up to 30–40% of patients experience persistent symptoms and/or ongoing mucosal injury despite reported compliance. This therapeutic gap, combined with advances in molecular understanding of disease mechanisms, has driven the development of novel strategies targeting key pathogenic pathways. Intraluminal interventions include gluten-degrading enzymes and gluten-sequestering agents, while other approaches target tissue transglutaminase 2, induce antigen-specific immune tolerance, or modulate cytokine-driven inflammation, with particular emphasis on interleukin-15 (IL-15) signaling. Additional strategies aim to inhibit lymphocyte trafficking to the intestinal mucosa and enhance intestinal barrier function through zonulin modulation. Adjunctive therapies under investigation include nutraceuticals, microbiota-targeted interventions, and vaccine-based approaches. More recently, advanced experimental and computational platforms, such as human intestinal organoids, organ-on-chip systems, and machine learning–driven analytics, are being leveraged in efforts to accelerate translational research and support the rational design of precision medicine approaches. This narrative review synthesizes current evidence for therapies beyond the GFD, examines challenges in clinical implementation, and discusses how technological innovations may reshape the future therapeutic landscape of CeD. Full article

Introduction: Children with chronic kidney disease (CKD) are susceptible to infections due to impaired immunity, immunosuppressive treatments, and dialysis, which lead to increased mortality, morbidity, and hospitalization rates. Immunization is an efficient preventive strategy, but despite the long-existing guidelines, vaccination rates of children with CKD remain suboptimal. Aim: This review aims to summarize the available data on vaccine-preventable infection morbidity and vaccination coverage in children with CKD, the reasons of vulnerability and suboptimal vaccination of this population and strategies that have been proposed for their overcoming. Results: Vaccination coverage studies for children with CKD are limited and outdated but, despite their variability, they confirm suboptimal vaccine coverage. The vulnerability of children with CKD to infectious dis-eases has been better understood with advanced molecular studies of their immune re-sponse. Several barriers, some of them unique to this population, hamper adherence with vaccination guidelines. Targeted interventions at different levels that have already been tried in adults with CKD, such as enhanced communication with families, cocooning strategies for the most vulnerable, education of specialists on vaccines, and organization of vaccination teams, seem promising in improving vaccination rates and infection prevention. Conclusions: The suboptimal protection from infections of children with CKD can be improved with prioritization of vaccination in their complicated care. Full article

Epizootic hemorrhagic disease (EHD) is an important livestock disease caused by Epizootic hemorrhagic disease virus (EHDV). The recent incursion and wide distribution of EHDV in Europe have increased the need for effective vaccine candidates. Background/Objectives: The VP2 protein of EHDV forms the outer capsid layer of the virion and is essential for viral assembly and host cell entry. Owing to its antigenic properties, VP2 represents a major target for vaccine development. However, the recombinant production of VP2 is limited by low stability and poor yields, representing a significant barrier for the generation of safe and effective subunit vaccines. Methods: To overcome these limitations, the VP2 protein from EHDV serotype 8 (EHDV-8) was rationally engineered with targeted modifications at both the amino and carboxyl termini of its coding sequence. Recombinant expression was performed using a baculovirus vector-mediated system in Trichoplusia ni pupae (CrisBio^® technology), employed as living biofactories. Results: The engineering of VP2 resulted in up to a tenfold increase in protein yields compared with the wild-type sequence, while maintaining the trimeric structural integrity of the recombinant protein. Both wild-type and engineered VP2 protein variants were formulated and used to immunize IFNAR(−/−) mice, a model susceptible to EHDV infection. Both engineered and wild-type VP2 formulations elicited comparable neutralizing antibody responses in vaccinated animals. Furthermore, immunization with either formulation conferred full protection against lethal EHDV-8 challenge. Conclusions: In this work, we demonstrated that the rational engineering of the VP2 protein significantly improved recombinant expression yields in a baculovirus-based system without compromising structural integrity or immunogenicity. These findings additionally demonstrate the feasibility of producing high-quality VP2 antigens in T. ni pupae using CrisBio^® technology and support their potential application in the development of subunit vaccines against EHDV. Full article

Background: Childhood immunization is one of the most effective public health strategies for reducing morbidity and mortality from vaccine-preventable diseases. Although overall vaccination coverage in the United States remains high, disparities persist across socioeconomic and healthcare access groups. Understanding these disparities is particularly important in the post-COVID-19 era, when increased vaccine hesitancy may threaten progress in maintaining equitable coverage. Materials and Methods: We analyzed data from the National Immunization Survey–Child (NIS-Child), focusing on U.S. children aged 19–35 months in 2023, corresponding to cohorts reaching this age during or after the COVID-19 pandemic. The primary outcome was receipt of the up-to-date combined 7-vaccine series (4:3:1:3:3:1:3: ≥4 doses of DTaP, ≥3 doses of polio, ≥1 dose of measles-containing vaccine, full Hib series, ≥3 doses of hepatitis B, ≥1 dose of varicella, and ≥3 doses of PCV). Logistic regression models were used to estimate associations between vaccination coverage and key explanatory variables: household income-to-poverty ratio, maternal education, health insurance type, and provider facility type, controlling for demographic and regional covariates. Disparities were quantified using concentration indices (CIs). Results: Among children in the analytic sample, overall coverage for the 7-vaccine series was only 78.5%. Nonetheless, disparities were evident. Children from households with lower income-to-poverty ratios (<1 × FPL: OR = 0.44, 95% CI = 0.37–0.53; 100–200%: OR = 0.66, 95% CI = 0.56–0.79), those covered by Medicaid (OR = 0.54, 95% CI = 0.45–0.64), other insurance (OR = 0.48, 95% CI = 0.37–0.61), or uninsured (OR = 0.27, 95% CI = 0.18–0.42), and those whose mothers had lower educational attainment (<12 years: OR = 0.35, 95% CI = 0.28–0.44) had significantly lower odds of being up-to-date. Similar associations were observed across specific vaccines. Unadjusted CIs for income-to-poverty ratio (0.04, p < 0.01), maternal education (0.04, p < 0.01), health insurance (0.03, p < 0.01), and provider type (0.03, p < 0.01) decreased but remained statistically significant after adjustment (0.02, 0.02, 0.01, and 0.02, respectively; all p < 0.01). No significant disparities were found by census region or race/ethnicity. Discussion: Despite relatively high overall vaccination coverage among U.S. children born during and after the COVID-19 pandemic, disparities by socioeconomic and healthcare access factors persisted. However, the absolute magnitude of these disparities was very small (concentration indices ≤ 0.04). These findings suggest that while inequities remain statistically measurable, their scale is limited in absolute terms. Targeted efforts to address income, insurance, maternal education, and provider-related barriers will be important to sustain equitable immunization coverage in the post-pandemic era. Full article

Background: Socioeconomic disparities may affect COVID-19 booster vaccination uptake, potentially undermining public health efforts. This study assessed the association between first booster dose coverage and municipal socioeconomic deprivation in the Apulia region of southern Italy. A secondary objective was to evaluate whether SARS-CoV-2 incidence modified this relationship. Methods: We conducted a retrospective observational study including Apulian residents aged ≥5 years from 1 January 2021, to 31 December 2022. First booster doses were identified using an algorithm based on dose chronology and national guidelines. Vaccination and infection data were retrieved from regional databases. Socioeconomic deprivation was measured using the Social and Material Vulnerability Index (SMVI) developed by the Italian National Institute of Statistics (ISTAT). Booster coverage was calculated at the municipal level. A multivariable Poisson’s regression model was used to estimate the association between SMVI and booster uptake, adjusting for age group, primary vaccine type, SARS-CoV-2 incidence, and municipal vaccination rates. Analyses were stratified by sex. Results: A total of 2,732,258 individuals received a first booster dose. Booster coverage decreased with increasing SMVI. Among females, a significant reduction was observed in the highest deprivation category (RR > 102 vs. <99: 0.95; 95% CI: 0.94–0.97) and it was similar in males (RR: 0.95; 95% CI: 0.93–0.96). A significant interaction between age and deprivation was found in both sexes, with a sharper decline in younger individuals. Municipal vaccination rates were positively associated with booster uptake. SARS-CoV-2 incidence was positively associated with uptake only in males. Conclusions: The analysis revealed a significant association between lower socio-cultural level and lower adherence to the first booster dose of the COVID-19 vaccine. The decline is more pronounced among subjects younger than 50 years with high levels of vulnerability. The findings of this study suggest that to overthrow vaccine hesitancy, knowledge of the social setting allows for targeted communications to the different groups in the population. Further research is needed to define different approaches in the different social groups. Full article

Background/Objectives: Cervical cancer is the second most common gynecological cancer worldwide, preventable through screening initiatives and vaccinations against its causative agent, anogenital human papillomavirus (HPV). This study aimed at measuring the coverage and uptake of the national HPV vaccination program launched in 2023 and implemented throughout Poland. Methods: This cross-sectional, observational study analyzed population data of adolescents in 11–13-year-old groups vaccinated in individual voivodeships (provinces) of Poland as provided by the National Health Fund and the Central Statistical Office. A p-value of <0.05 was considered statistically significant. Results: The rate of HPV vaccination participation under the population program was 8.67%. In the analyzed age groups, in both sexes, no statistically significant correlation was observed between the population size at a given age and population coverage or participation in HPV vaccination. However, a positive relationship in vaccination coverage was observed in individuals previously vaccinated with one dose in subsequent age groups, indicating a continued willingness to receive vaccination with further doses. No statistically significant difference in population coverage changes across voivodeships was found between the number of doses within the urban population share vs. rural population share. Conclusions: Our results show that, at 1.5 years of implementation of the national HPV vaccination program, the coverage and uptake of the program is considerably insufficient. The intensive corrective actions indicated are required to pave this program forward towards optimum results. Full article