Search Results (1,686)

Human papillomavirus (HPV) infection remains a major global health challenge, particularly when persistent high-risk genotypes lead to oncogenic progression. While prophylactic vaccines are effective, their role in accelerating the clearance of existing infections is still being explored. This study aimed to investigate the potential efficacy of adjunctive Pidotimod therapy combined with the nonavalent HPV vaccine in reducing persistent genotypes and promoting clearance in men. This retrospective pilot study included 23 HIV-negative men with anal and/or genital HPV infections. Participants were divided into two groups: 7 received the standard nonavalent HPV vaccine alone (control), and 16 received oral Pidotimod (800 mg twice daily for 10 days surrounding each vaccine dose) in addition to the vaccine (treatment). HPV genotyping (28 types) was performed at baseline and 12 months using real-time PCR. At 12 months, the HPV-negative conversion rate was 62.5% in the Pidotimod + vaccine group compared to 28.6% in the control group (p = 0.19). While this primary difference in total clearance was not statistically significant due to the limited sample size, the treatment group showed a substantial per-patient reduction in the number of persistent genotypes, decreasing from a mean of 2.75 ± 2.05 to 0.50 ± 0.82, compared to a decrease from 3.43 ± 2.37 to 1.86 ± 1.07 in the control group. The Pidotimod group achieved a significantly lower number of persistent genotypes at 12 months compared to the control group (p = 0.008, Mann–Whitney U test). Additionally, the use of pre-exposure prophylaxis (PrEP) was significantly associated with a lower rate of HPV clearance (12.5% vs. 73.3%, p < 0.01). Adjunctive therapy with Pidotimod suggests a promising trend in facilitating the reduction in HPV strain burden when combined with the HPV vaccine in men. While larger prospective studies are needed to confirm these effects, this exploratory approach could represent a promising immunomodulatory strategy for managing multiple and persistent HPV infections, even in high-risk groups such as PrEP users. Full article

Mayaro virus (MAYV) is an emerging arbovirus from the Togaviridae family where inflammation plays a central role in disease development. As the cause of Mayaro fever, MAYV triggers strong production of pro-inflammatory cytokines, which can result in long-lasting arthralgia in affected individuals. Macrophages are both targets for viral infection and key regulators of inflammatory responses. Human monocyte-derived macrophages (MDMs) are susceptible to MAYV infection in vitro and support productive viral replication. With no approved antivirals or vaccines, finding host-directed therapies is an urgent priority. Cannabinoids are compounds with antiviral and immunomodulatory properties, suggesting potential against MAYV infection. Here, we examined the effects of cannabidiol (CBD) and the synthetic cannabinoid WIN 55,212-2 on MAYV-infected MDMs in pre- and post-treatment conditions. Cells and supernatants were collected at 6 and 24 h post-infection (h.p.i). To understand the mechanisms involved, transcriptomic and functional analyses were performed at 24 h.p.i in the post-treatment setting, focusing on inflammatory, antiviral, and endoplasmic reticulum (ER) stress pathways. WIN 55,212-2 post-treatment significantly decreased viral replication at 24 h.p.i without any direct virucidal activity and was independent of type I interferon activation or interferon-stimulated gene induction, instead being linked to the modulation of ER stress signaling. Specifically, WIN 55,212-2 increased IRE-1α RNase activity, promoting the alternative splicing of sXBP1, while the integrated stress response appeared central to its antiviral effect. Additionally, WIN 55,212-2 downregulated inflammation-related genes and altered cytokine and chemokine production, counteracting the strong inflammatory response caused by MAYV. Remarkably, it also exerted broader immunomodulatory effects independent of infection. Full article

Background/Objectives: Technology transfer (TT) has been identified as a global health priority due to its impact on improving access to vaccines, including for pandemic influenza preparedness and response through bilateral and multilateral mechanisms. This study aimed to (1) characterize examples of influenza vaccine TT (IVTT) and (2) identify key lessons learned that may inform future activities relevant for next-generation influenza vaccine technologies. Methods: Using a contingent effectiveness model, a convergent mixed-methods study was conducted with vaccine manufacturers and global experts to capture quantitative survey data on IVTT activities and enablers and qualitative data on successes, challenges, and opportunities for IVTT through interviews, complemented by secondary data from peer-reviewed and grey literature to characterize additional IVTT observations. Results: This study included 24 participants, including 14 representatives from 13 vaccine manufacturers and 10 experts. Interviews were conducted with representatives from eight manufacturers and seven experts. Eighteen IVTT observations were identified through the surveys and interviews, of which 15 IVTT transfers were completed and 13 resulted in an approved vaccine. Secondary data provided additional evidence on eight IVTT recipients and one supplier, expanding the range of institutional and programmatic contexts assessed. Shorter IVTT completion and vaccine approval timelines were observed in association with prior TT experience and private management structures for manufacturers, for pre-pandemic/pandemic influenza vaccines versus seasonal influenza vaccines, and among bilateral transfer mechanisms (versus multilateral mechanisms) and fill/finish transfer methods. Manufacturers also described spillover benefits, including the use of IVTT-related know-how for the development of COVID-19 and routine vaccines. Both manufacturers and experts generally agreed on a list of 17 enablers for successful IVTT and ranked government commitment to vaccine production and procurement as the top enabler. Findings from the literature-based observations were consistent with primary data and included additional public sector recipient experiences, evidence of widespread human capital development, and a commentary on the importance of the demand environment. Conclusions: Assessed IVTT activities across primary and secondary data sources yielded commercial and spillover benefits as described in the contingent effectiveness model and provided a triangulated analysis of IVTT experiences across manufacturers, experts, and documented cases. Participants agreed that effective technology transfer is contingent upon a host of determinants. Using a systematic application of the contingent effectiveness model to IVTT, this study provided an exploratory analysis of past activities among vaccine manufacturers and experts. While certain nuances for influenza were identified, the lessons learned from this study may be applicable for other TT activities, including those to support pandemic preparedness. The contingent effectiveness model is a useful tool to inform and evaluate future TT activities. Full article

Background/Objectives: Immunonutrition uses dietary bioactive compounds to support immune function while preserving systemic physiological balance. Donkey milk, bovine colostrum, and royal jelly contain complementary antimicrobial, immunoglobulin-rich, and immunoregulatory components, but their combined effects remain insufficiently characterized. Methods: A 6-week controlled study was conducted in female rabbits assigned to four groups (n = 15/group): vaccinated only (G1), immunonutraceutical only (G2), vaccination plus immunonutraceutical (G3), and pre-conditioned immunonutraceutical followed by vaccination and continued supplementation (G4). Serum total immunoglobulins and lysozyme were measured longitudinally. Biochemical indices were monitored throughout the study, and hematological parameters were evaluated at the final time point. Mixed-effects models, generalized estimating equations, principal component analysis, and correlation-based systems analyses were applied. Results: Supplementation significantly modulated both humoral and innate immune responses. The strongest terminal immunoglobulin response was observed in G4 (26.00 ± 5.80 mg/mL), whereas sustained lysozyme elevation was most pronounced in supplemented groups, particularly G3 (3.13 ± 0.44 ng/mL). Within-subject analysis demonstrated significant innate–adaptive immune coherence (p = 0.000006). Biochemical analyses showed coordinated metabolic adaptation without evidence of organ toxicity, and hematological findings indicated preserved inflammatory and hematopoietic stability. Conclusions: Multi-component immunonutraceutical supplementation modulated humoral and innate immune dynamics in a timing-dependent manner while maintaining biochemical and hematological safety. These findings support the potential of combined donkey milk, bovine colostrum, and royal jelly as functional ingredients for coordinated immune support. Full article

Schmallenberg virus (SBV) has evolved from an emergent Orthobunyavirus identified in Europe in 2011 into an endemic pathogen with complex epidemiological dynamics. This review focuses on three key aspects: pathogenesis and fetal neurotropism, diagnostic limitations within the Simbu serogroup, and challenges in disease control. SBV pathogenesis is characterized by immune evasion mediated by the NSs protein and a marked tropism for the developing central nervous system, resulting in congenital malformations when infection occurs during critical gestational stages. Similar mechanisms are shared with other Simbu serogroup viruses, contributing to overlapping clinical presentations and complicating differential diagnosis. Diagnostic approaches are constrained by the short duration of viraemia and significant serological cross-reactivity among related viruses. While RT-qPCR is effective for detecting acute infections, its utility is limited for retrospective diagnosis, where fetal tissues and pre-colostral serology are required. Widely used ELISAs lack serogroup specificity, raising concerns about the potential under-recognition of co-circulating or emerging viruses. Despite advances in vaccine development, implementation remains limited, and vector control strategies provide only partial mitigation. SBV therefore represents a valuable model for understanding arbovirus persistence in temperate regions. Addressing current challenges will require improved diagnostic specificity, sustainable vaccination strategies, and integrated surveillance systems. Full article

Background/Objectives: Girls living with HIV (GLHIV) or vulnerable to HIV have a higher risk of HPV infection and cervical cancer as they age. We determined acceptability and vaccination uptake after integrating HPV vaccination into HIV prevention and treatment services for girls in Mozambique and Zimbabwe. Methods: Pre-integration and integration HPV vaccination information were abstracted from routine records of girls aged 9–14 years offered HPV vaccine through HIV services in 54 health facilities (HFs) and surrounding communities between February and December 2025. Caregivers participated in quantitative surveys about vaccine perceptions and integration model experiences in a subset of 16 HFs. Results: In total, 6377 records of girls (median age: 11 years) were abstracted. Among the vaccine recipients, 63 (3.0%) girls received vaccine pre-integration and 2019 (97.0%) post-integration in Mozambique and 743 (17.3%) pre-integration and 3541 (82.7%) post-integration in Zimbabwe. Among GLHIV, 95.8% and 69.6% received a first HPV vaccine in Zimbabwe and Mozambique, respectively. Full vaccination with two doses occurred in 49.1% of eligible girls in Mozambique and 73.9% in Zimbabwe. Overall, 461 (67.8%) caregivers had heard of the HPV vaccine and 85.9% of cervical cancer, 99.6% were satisfied with vaccination in integration settings, and 78.6% preferred facility-based vaccination models. Conclusions: We demonstrated that HPV/HIV service integration was an effective strategy to increase HPV vaccine uptake among young girls at increased risk of HPV and cervical cancer. We found high vaccine and model acceptability and awareness of cervical cancer among caregivers. Optimization of this approach requires better integrated tools and model adaptations to fit the needs of girls and health systems. 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

Background: Epidemiological alerts about the possible spread of different pathogens have highlighted the risk of international travelers contracting infectious diseases when visiting endemic areas. The role of travelers in disease transmission underscores the importance of pre-travel consultations, which provide critical information on health risks, vaccinations, and preventive measures. Understanding travelers’ risk perceptions and behaviors is essential for enhancing global health security in the post-pandemic era. Methods: A cross-sectional study (June 2023–January 2024) was conducted by administering an anonymous questionnaire at the Rome-Fiumicino Airport International Prophylaxis Clinic (USMAF-SASN). The questionnaire explored demographics, travel patterns, risk perceptions, vaccination behaviors, and sources of health information. Descriptive statistics and a multivariable logistic regression analysis were performed to identify low-risk perception predictors. Results: Among 217 participants, 89.8% were Italian, with a balanced representation of genders. The primary purpose of travel was tourism (61.6%), followed by work-related trip (23.1%). While 77.1% rated preventive measures as effective, 23.2% evaluated infection risk as low. Being male (aOR 3.63, 95% CI 1.37–9.61), and being a hotel user (aOR 6.27, 95% CI 2.43–16.15), was significantly associated with a lower risk perception. As expected, healthcare professionals and individuals using institutional healthcare sources showed a higher risk awareness. Vaccination uptake at the Airport Clinic was motivated by self-protection, vaccine confidence, and poor time flexibility to access local vaccination services, and last-minute plans, making the airport a more convenient option. Conclusions: Travelers’ risk perception is influenced by gender, profession, accommodation type, and information sources. Public health strategies should enhance health literacy, promote pre-travel consultations, and improve access to preventive services. Strengthening collaborations between health authorities, educational institutions, and the travel sector is key to mitigating health risks and ensuring global health security. Future interventions should address structural vaccination barriers and improve outreach to under-informed travelers. Full article

Background: Vaccination coverage declined in many countries during the COVID-19 pandemic, including in Bosnia and Herzegovina. We evaluated a telephone-based outreach intervention implemented in primary healthcare facilities (PHCs) in the Federation of Bosnia and Herzegovina. The intervention targeted missed routine vaccinations among children aged 0–7 years. Method: Using a programmatic, non-randomized pre–post design, healthcare teams reviewed registries to identify under-vaccinated children, and parents were contacted by phone to facilitate catch-up visits. Results: Among age-eligible children, vaccination coverage increased from 66.5% to 74.2% for measles–mumps–rubella (MMR) dose 1, from 43.4% to 51.7% for MMR dose 2, and from 50.4% to 55.9% for the fourth dose of diphtheria–tetanus–acellular pertussis-inactivated poliovirus–Haemophilus influenzae type b vaccine (DTaP-IPV-Hib). Mixed-effects models adjusting for age, sex, and clustering by facility and canton showed higher odds of vaccination post-intervention for MMR dose 1 (adjusted odds ratio [aOR] 1.65), MMR dose 2 (aOR 1.61), and DTaP-IPV-Hib dose 4 (aOR 1.39; all p < 0.001). Conclusions: These results show that registry-based, proactive outreach can yield significant improvements in routine childhood vaccination coverage in real-world settings and may be a scalable approach for decentralized health systems recovering from pandemic disruptions. Full article

This perspective outlines the ongoing necessity for an HIV vaccine and immune-based prevention strategies in an era of availability of multiple behavioral and pharmacological HIV prevention interventions, including safe and highly effective pre-exposure prophylaxis (PrEP). We describe the approach of the National Institute of Allergy and Infectious Diseases (NIAID), Division of AIDS (DAIDS), based on key scientific progress, critical steps, and persistent challenges in achieving broad and durable immune protection against HIV. We highlight DAIDS coordinated infrastructure, clinical trial networks, and partnerships that enable iterative development and de-risk innovation for these interventions. Finally, we consider implications for trial design and priorities for advancing scalable HIV immune-based prevention. Full article

Oncolytic viruses (OVs) exploit key hallmarks of cancer to selectively replicate in malignant cells, leading to tumor cell lysis, modulation of the tumor microenvironment, and induction of antitumor immunity. These viral platforms have been engineered to enhance tumor specificity, intratumoral spread, and immunotherapeutic efficacy. Among them, rhabdoviruses, particularly vesiculoviruses, have emerged as promising candidates due to their rapid replication, high titers, and amenability to genetic manipulation. Maraba virus, a recently identified vesiculovirus, is a single-stranded negative-sense RNA virus with a favorable safety profile and minimal pre-existing immunity in humans. It demonstrates selective tumor tropism partly through low-density lipoprotein receptor (LDLR)-mediated entry and impaired antiviral responses in cancer cells. Genetic engineering of the wild-type Maraba virus led to the development of the MG1 strain, characterized by enhanced tumor selectivity, increased replication capacity, and potent cytolytic activity. Preclinical studies have demonstrated its efficacy as a monotherapy, a cancer vaccine vector expressing tumor-associated antigens, and in combination with chemotherapy and immune checkpoint inhibitors. MG1 also reshapes the tumor microenvironment, converting immunologically “cold” tumors into “hot” tumors, thereby enhancing immune-mediated tumor clearance. Compared to vesicular stomatitis virus, Maraba virus exhibits improved safety and reduced neurovirulence while maintaining strong oncolytic potential. This review aims to comprehensively summarize the biological characteristics of the MG1 Maraba virus, its genetic development, mechanisms of action, and current preclinical and clinical applications as a novel oncolytic immunotherapeutic agent. Full article

Acute gastroenteritis (AGE) remains a leading cause of pediatric mortality and morbidity, with rotavirus as the leading cause of severe disease. Post-vaccine surveillance is essential to monitor circulating pathogens and assess vaccination impact. Sicily was the first Italian region to implement universal rotavirus vaccination in 2012. We retrospectively studied 693 children hospitalized for suspected viral AGE at the Children’s Hospital of Palermo (March 2017–February 2020), testing stool samples for viral and bacterial enteric pathogens. Rotavirus remained the most common agent (13.3%), followed by norovirus (12.1%), adenovirus (11.3%), Salmonella spp. (4.6%) and astrovirus (3.2%). The study population was categorized as rotavirus-associated AGE (RV-AGE) or other-cause AGE (O-AGE). Epidemiological, clinical and virological features were compared with the pre-vaccine period (2011–2012). At least one pathogen was detected in 47.5% of samples. RV-AGE cases were older than those with O-AGE (median 32.6 vs. 30.5 months; p < 0.01) and had greater clinical severity, with higher frequency of vomiting, fever and dehydration. Rotavirus infection was significantly associated with unvaccinated status. Compared with the pre-vaccine era, rotavirus prevalence declined (32.6% vs. 13.3%), seasonal patterns were attenuated and genotype distribution shifted toward G2P[4], G9P[8] and equine-like G3P[8] strains. Despite the decline in RV-AGE following vaccine introduction, rotavirus remains a relevant cause of pediatric AGE, underscoring the need for high vaccination coverage and continued surveillance. Full article

Chronic respiratory diseases (CRDs) represent a significant global mortality burden, largely driven by viral-triggered exacerbations. In the elderly, susceptibility to viral pathogens is critically linked to the “interferon gap”—a kinetic delay in innate antiviral signaling resulting from immunosenescence and Th2-skewed inflammaging. While traditional vaccines provide pathogen-specific protection, their efficacy is often compromised by age-related immune hyporesponsiveness and antigenic drift. This perspective paper proposes a dual-phase, virus-agnostic immunomodulatory platform designed to restore mucosal immune competence and provide a rapid-response intervention for incipient exacerbations. Rather than acting as a pathogen-specific vaccine, the platform serves as a comprehensive host immune-rejuvenation engine and cellular adjuvant platform. The platform consists of two integrated stages: Allopriming and Alloantigen Inhalation Recall (AIR). Allopriming utilizes AlloStim^® (activated, allogeneic Th1 cells) to leverage the evolutionarily conserved allo-rejection response, establishing a lung mucosal reservoir of allo-specific Th1 tissue-resident memory cells (Trm). Building on previously published Phase I/II data showing that Allopriming reverses biomarkers of immunosenescence and sustains durable heterologous antiviral responsiveness, the AIR strategy is introduced as a patient-administered rescue mechanism for frail CRD patients. AIR is designed to activate pre-positioned Trm cells at the earliest onset of symptoms, inducing a high-magnitude IFN-γ surge in the lung mucosa. By bridging the senescent “interferon gap” with the rapid effector kinetics of Trm activation, this approach represents a novel paradigm toward reconstituting youthful-like antiviral mucosal immunity to both enhance vaccine efficacy in the elderly and protect against both seasonal pathogens and emerging viral triggers (“Disease X”) of CRD. Future randomized studies in long-term care settings are planned to evaluate clinical outcomes in high-risk populations. Full article

Background: In March 2026, a meningococcal cluster centred on the University of Kent, England, caused two deaths and resulted in over 20 reported cases within the first week, including confirmed and suspected invasive cases. Subsequent UKHSA updates in early April 2026 reported 21 laboratory-confirmed MenB cases (18 linked to the outbreak strain) and two deaths, with the outbreak subsequently spreading to a second Canterbury university, Canterbury Christ Church University, and confirmed as Neisseria meningitidis serogroup B (MenB). Sub-Saharan Africa (SSA) bears a disproportionate global burden of meningococcal disease, yet university settings remain a critically understudied outbreak amplifier. This narrative review extracts epidemiological and policy lessons from the Kent event and applies them to the SSA context. Methods: We conducted a narrative review following the SANRA criteria, searching PubMed, Embase, Scopus, Google Scholar, and African Journals Online (2000–2026), with supplementary grey literature retrieved from World Health Organisation (WHO), Africa Centre for Disease Control, and United Kingdom Health Security Agency (UKHSA). Outbreak data were drawn from official UKHSA public-health statements (grey literature, archived), the University of Kent communications, and peer-reviewed expert commentary. Results: The Canterbury outbreak exposed six reproducible vulnerabilities: unprotected serogroup circulation (confirmed MenB, not covered for the current university-age cohort), nightlife-linked transmission amplification, delayed serogroup identification, poor student symptom-recognition, inadequate institutional response capacity, and, critically, multi-institutional spread via shared nightlife venues (confirmed extension to Canterbury Christ Church University within five days). Each vulnerability is demonstrably more severe in SSA universities, which face a broader multi-serogroup threat environment (NmA, B, C, W, X), virtually no university-entry vaccination requirement, and critical evidence gap of campus-specific meningococcal evidence in the published literature. Conclusions: This review proposes a five-pillar preparedness framework for SSA tertiary institutions, derived from a synthesis of the Kent outbreak and broader epidemiological evidence, intended to inform policy discussion and future research. Moreover, these should be embedded within a broader age-linked prevention strategy that begins before university entry, particularly during the transition into secondary school in high-risk settings. Priority measures include meningococcal vaccination at key educational transition points, prophylactic antibiotic pre-positioning, serogroup-capable surveillance, symptom-recognition training, and pan-continental alert A predominantly reactive response may carry substantial risk in SSA settings. Full article