Search Results (624)

Dendritic cells (DCs) are critical antigen-presenting cells that orchestrate the interface between innate and adaptive immunity, making them attractive approaches for cancer immunotherapy. Recent advances in the characterization of DC subsets, antigen delivery strategies, and adjuvant design have enabled the enhancement of DC-based vaccines for solid tumors. Clinical studies across melanoma, glioblastoma, prostate cancer, and non-small cell lung cancer have demonstrated safety and immunogenicity, with encouraging signals of clinical efficacy, particularly when DC vaccination is combined with immune checkpoint blockade or personalized neoantigen approaches. However, translational barriers remain, including the immunosuppressive tumor microenvironment, inefficient DC migration, and variability in manufacturing protocols. Developing solutions such as in vivo DC targeting, biomaterials-based delivery systems, high-resolution single-cell analyses, and artificial intelligence-driven epitope prediction are controlled to overcome these challenges. Together, these innovations highlight the evolving role of DC immunotherapy as a foundation of precision oncology, offering the potential to integrate personalized vaccination strategies into standard treatment paradigms for solid tumors. Therefore, in this review, we specifically focus on these advances in dendritic cell immunotherapy for solid tumors and their translational implications. Full article

Background: Hyaluronic acid (HA) dermal fillers are among the most widely used injectable materials in esthetic medicine. They are generally safe, but delayed inflammatory reactions (DIRs) have been observed, particularly after viral infections or vaccinations. Such events have raised questions about the role of immune activation in filler-related complications. Objective: This review examined the available literature on DIRs to HA fillers that occurred in the context of viral illness or immunization, with attention to how these reactions present and how they are managed. Methods: A systematic search was carried out in PubMed, ScienceDirect, ClinicalKey, and Google Scholar between October and November 2024. Only human case reports and case series were included. The protocol was registered in PROSPERO (CRD420251030918), and study quality was assessed using the Newcastle–Ottawa Scale. Results: Six publications met inclusion criteria: four case series and two case reports, describing 25 women between 22 and 65 years of age. Patients developed swelling, erythema, angioedema, or, in severe cases, marked facial edema after HA filler injections, with symptom onset ranging from several hours to several weeks following viral exposure. Corticosteroids and hyaluronidase were the most common treatments, though milder cases sometimes resolved without intervention. Study quality varied, with some reports providing limited detail on patient characteristics and follow-up. Conclusions: DIRs associated with viral infections or vaccinations remain uncommon but clinically relevant complications of HA filler use. Limited case-based evidence indicates potential effectiveness of corticosteroids and hyaluronidase, though management practices remain inconsistent. Larger prospective studies are needed to clarify underlying mechanisms and to establish standardized guidelines for treatment. Full article

Background: The current assessment method of the protective efficacy of adjuvanted vaccines remains slow and labor-intensive, hindered by prolonged immunization protocols and complex assays. Methods: To overcome this bottleneck, we demonstrate that early segregated cellular biomarkers enable rapid prediction of protection, using a respiratory syncytial virus (RSV) pre-fusion F (pre-F) protein model with diverse adjuvants in mice. Results: We identified that germinal center (GC) B cell responses (Days 7 and 9 post-immunization) strongly aligned with protective efficacy, except for Alum, which achieved MF59-level protection despite lower GC responses. Crucially, follicular dendritic cell (FDC) abundance at day 7 universally predicted protection across all adjuvants, including Alum, drastically shortening discovery time and effort from at least 4–6 weeks to within 1 week. Conclusions: FDCs and GC B cells serve as complementary early biomarkers that accurately forecast vaccine efficacy. This approach could potentially reduce the need for prolonged immunization regimens by cellular profiling on days 7–9, offering a modest step toward streamlining adjuvant selection and informing vaccine design. Full article

Background/Objectives: Bluetongue virus (BTV) is an emerging arbovirus causing significant economic losses in the ruminant industry. Current vaccines offer limited cross-protection against heterologous serotypes and do not enable differentiation between infected and vaccinated animals (DIVA). Subunit-based vaccines provide a potential DIVA-compatible solution. This study aimed to develop a vaccination protocol expressing BTV structural proteins VP7 or VP2 using antibiotic-resistance-free DNA plasmids and replication-defective adenovirus vectors. Methods: We evaluated homologous DNA prime–boost and heterologous DNA prime–adenovirus boost strategies in a murine model, assessing adaptive immune responses and protection against virulent BTV challenge. Results: The heterologous DNA–adenovirus prime–boost strategy expressing both antigens conferred full protection, preventing viremia, while homologous DNA-DNA prime–boost provided only partial protection. Both VP7 and VP2 elicited cellular and humoral immune responses, but the heterologous strategy significantly enhanced anti-BTV IgG, neutralizing antibody titers, and T cell activation. CD8⁺ T cell responses showed the strongest correlation with viral load reduction, suggesting that cellular immunity to conserved VP7 could serve as a platform for cross-protection against multiple BTV serotypes. Conclusions: These findings highlight the potential of heterologous DNA–adenovirus vaccination as an effective DIVA-compatible strategy for BTV control. By inducing strong and protective immune responses, this approach could improve disease surveillance and management, ultimately reducing the impact of BTV on livestock industries. Full article

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to evolve, with mutations leading to the emergence of new variants. JN.1, a subvariant of omicron BA.2.86, has demonstrated marked immune escape and is now included in updated vaccine formulations. While reduced sensitivity has been reported for antibody assays using ancestral spike protein subunits to detect omicron-induced responses, the performance of full-length spike-based assays against omicron sublineages remains unclear. We aimed to compare the sensitivity of ELISA and Luminex assays using full-length spike proteins from the ancestral Wuhan strain and the JN.1 variant. Methods: Wuhan and JN.1 full-length spike protein constructs were designed and expressed in Expi293F mammalian cells. In-house ELISAs based on previously validated protocols were used to measure anti-spike IgG levels. Additionally, a Luminex-based assay for anti-spike antibody detection was developed and validated. Both assays were applied to the following sample groups: pre-pandemic samples (designated “gold standard negatives”); PCR confirmed 2020 positives (“gold standard wildtype positives”); PCR confirmed 2024 positives (“gold standard omicron positives”); 2022 vaccinated individuals with verbal confirmed infection (“gold standard hybrid positives”); and 2024 household samples (“unknowns”). Results: Wuhan spike protein showed a sensitivity of 100% (95% CI: 0.88–1.0) in detecting omicron-specific antibodies using gold standard omicron positives with JN.1 spike protein as a reference assay. Overall, across all samples, in ELISA, the Wuhan antigen had a sensitivity of 0.93 (95% CI: 0.89–0.95) and a specificity of 0.98 (95% CI: 0.94–0.99). The JN.1 antigen showed a sensitivity of 0.91 (95% CI: 0.87–0.94) and a specificity of 0.97 (95% CI: 0.93–0.99). In Luminex, sensitivity was 0.95 (95% CI: 0.91–0.97) for Wuhan and 0.94 (95% CI: 0.91–0.96) for JN.1. Specificity for both antigens in Luminex was 0.98 (95% CI: 0.94–0.99). Conclusions: Both ELISA and Luminex assays showed comparable sensitivity and specificity for both Wuhan and JN.1 antigens, indicating that mutations in the JN.1 variant do not significantly impact assay performance. This suggests preserved antigenic recognition across variants. Full article

Background: The efficacy of a single oral dose of Ivermectin as prophylaxis for SARS-CoV-2 is uncertain. This trial sought to evaluate the effectiveness of a single oral low dose of Ivermectin to prevent SARS-CoV-2 infection or reduce symptoms if infection did occur. Methods: Asymptomatic community-dwelling adults were enrolled in this study within 72 h of close contact with a case of SARS-CoV-2. Participants were randomised, stratified by vaccination status and exposure site, to a single oral 200 µg/kg dose of Ivermectin or placebo. The primary outcome was conversion to a positive polymerase chain reaction (PCR) or rapid antigen test (RAT) for SARS-CoV-2 within 14 days of close contact. Secondary outcomes were restricted to those who met the primary outcome. They included the following: days alive free of symptoms in the 14 (DAFS1-14) and 28 (DAFS1-28) days following intervention and days from close contact until a positive PCR or RAT for SARS-CoV-2. Results: A total of 536 participants registered for this trial. Of these, 86 met inclusion criteria and were randomised. 68 adhered to the trial protocol and were included in the analysis. A total of 11/36 (Ivermectin arm) and 11/32 (placebo arm) met the primary outcome. After controlling for age and prior SARS-CoV-2 infection, the estimate (95% confidence interval (95% CI)) of the effect of Ivermectin (compared to placebo) on the absolute value of the proportion of participants converting to a positive PCR or RAT was −0.051 (−0.26 to 0.16), p = 0.63. After controlling for prior SARS-CoV-2 infection, age, body mass index, hypertension and lung disease, the average treatment effect (Ivermectin versus placebo) on DAFS1-14 was 2.5 days (95%CI 1.1 to 4.5), p = 0.036, and for DAFS1-28, was 2.3 days (95% CI 0.7 to 3.3), p = 0.35. The mean (standard deviation) number of days from close contact until a positive PCR or RAT was 5.0 (4.1) days for the Ivermectin group versus 2.6 (0.8) days for the placebo group. After controlling for age and prior SARS-CoV-2 infection, the average treatment effect (95%CI), Ivermectin versus placebo, on days from close contact until a positive PCR or RAT was 2.3 days (95% CI 1.1 to 3.4), p = 0.033. Conclusions: We did not demonstrate that a single oral low dose of Ivermectin administered to asymptomatic adults within 72 h of close contact with a case of SARS-CoV-2 prevents conversion to a positive PCR or RAT. However, the trial had a small sample size and does not exclude a clinically meaningful effect of Ivermectin on conversion to a positive PCR or RAT. Amongst those who did convert to a positive PCR or RAT, the use of Ivermectin significantly lengthened the time from close contact to conversion and increased the number of days alive free of symptoms following intervention. Full article

Background/Objectives: Although vaccinations are a priority for patients with cancer, achieving high coverage remains challenging. Evidence on effective strategies in oncology settings is still limited. This systematic review aimed to identify interventions to improve vaccination uptake or reduce hesitancy among cancer patients. Methods: A systematic search was conducted in PubMed, Embase, and Scopus, including studies published up to the end of 2023. The protocol was registered in PROSPERO (CRD42024511008). Results: Out of 10,927 non-duplicate records, 15 studies describing unique interventions were included. All studies were published between 2011 and 2022, primarily conducted in Europe/UK (40%) and in North America (40%). The most common study design was pre-post (60%), and 33.3% included a control group. Most interventions were multi-component (60%) and were classified into three main categories: educational materials/campaigns (46.7%), reminders (40%), and patient counselling (33.3%). Additional components included guideline development in two studies. Some studies also highlighted the importance of specific key figures, such as dedicated professionals, general practitioners, and pharmacists. Interventions mainly targeted patients (40%), with 33.3% addressing both healthcare professionals and patients and 26.7% professionals only. They most frequently concerned vaccinations against influenza and pneumococcal disease (26.7%), pneumococcal disease alone (26.7%), or Coronavirus Disease 2019 (COVID-19) (26.7%). Vaccination uptake was the primary outcome in 86.7% of studies, with 66.7% reporting significant improvements. Conclusions: This review identified a variety of strategies, with education, reminders, and counselling as key components. Multicomponent interventions and those involving both patients and providers were most promising. However, methodological limitations and limited generalizability highlighted the need for more rigorous research. Full article

Introduction: Scrub typhus is caused by Gram-negative bacteria, Orientia tsutsugamushi. Humans are the dead-end host of scrub typhus. Currently, there is no vaccine available. The disease can be fatal without appropriate treatment. Here, we present the circulating OT genotypes in Malaysia and a tsa56-based single PCR to detect and determine OT genotypes, which is an approach to replace the time-consuming traditional nested PCR. Methods: The patients’ blood or tissue samples (n = 1200), received from all hospitals in Malaysia from December 2022 to November 2024, were screened for rickettsial infections. Both htrA qPCR and nested PCR were performed to detect the presence of OT DNA. Simultaneously, a selection of DNA was evaluated for the new single PCR protocol and confirmed with Sanger sequencing. Results: We report that Pahang state of Peninsular Malaysia presents the highest number of acute scrub typhus infections in Malaysia within the 24 months period. There are four genotypes circulating in the Malaysian population. OT genotype Gilliam (n = 31, 29.2%) and Karp (n = 31, 29.2%) are the predominant OT genotypes in Malaysia, followed by TA763 (n = 22, 20.8%) and Kato (n = 22, 20.8%). The single-run PCR presents longer sequence size and similar results with the nested PCR. Conclusions: Acute scrub typhus infection is not rare in Malaysia and should be considered for undifferentiated febrile illness. The single-run PCR protocol is time-saving and a promising approach for OT detection and genotype analysis in a single run to complement a clinical diagnostic setting and surveillance. Full article

Cervical cancer remains a significant public health challenge, disproportionately affecting women in low- and middle-income countries (LMICs). Persistent infection with high-risk types of human papillomavirus (HPV), particularly HPV16 and HPV18, is the central cause of cervical carcinogenesis, driven by the viral oncoproteins E6 and E7, which disrupt the host tumor suppressors p53 and retinoblastoma protein (pRb). Advances in molecular understanding have catalyzed effective primary and secondary prevention strategies. Prophylactic HPV vaccination, especially the nonavalent formulation, has demonstrated high efficacy in reducing HPV infections and cervical precancer. Concurrently, HPV deoxyribonucleic acid (DNA) testing, self-sampling, and screen-and-treat protocols are transforming screening paradigms, particularly in resource-limited settings. However, global disparities in vaccine access, screening coverage, and health infrastructure persist, impeding progress toward the World Health Organization’s (WHO) 90–70–90 elimination targets. By synthesizing recent advances in virology, prevention strategies, and implementation innovations, such as therapeutic vaccines, artificial-intelligence (AI)-driven diagnostics, and mobile health solutions, this review sheds light on their potential to narrow these equity gaps. Full article

Background: Characterization of cellular responses to vaccinations in immunocompromised patients remains an evolving area of research. This particularly applies for pneumococcal vaccination in diseases such as psoriasis and in the setting of immunosuppressive therapy. Methods: This prospective study included 42 patients with moderate-to-severe psoriasis. Following German guidelines at the time, patients underwent a sequential vaccination protocol against Streptococcus pneumoniae, consisting of Prevenar 13 (PCV13) and Pneumovax 23 (PPSV23). Over a 7-month period, we analyzed T-cell responses to common serotypes of Streptococcus pneumoniae using an interferon-γ ELISpot assay. For comparison, we performed an ELISA to measure pneumococcus-specific antibody production. Results: Patients undergoing anti-TNF-α blocker therapy, monoclonal antibody therapy (specifically anti-IL-12/23, IL-23, and IL-17), and methotrexate therapy showed significantly different responses to the pneumococcal serotype PS14 at onset (p = 0.02). T-cell responses ranged from strong (PS9N, PS14, PS25F) and intermediate (PS2) to weak (PS6A and PS11A). We did not observe a significant correlation of IgG antibodies with the magnitude of cellular immune responses. Conclusions: Immunosuppressive therapy alters vaccination-induced cellular immunity in psoriasis patients. Further research is needed to clarify the mechanisms involved. Full article

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by the clonal proliferation of myeloid precursors and rapid progression. Historically consisting of intensive chemotherapy, AML management has evolved significantly due to advances in molecular diagnostics and risk stratification. This review discusses current therapeutic paradigms in AML, emphasizing the growing role of personalized medicine across age and risk groups. For younger, fit patients, intensive regimens such as the “7 + 3” protocol remain the standard, often enhanced by targeted agents like FMS-like tyrosine kinase 3 (FLT3) and IDH inhibitors. Older or unfit individuals benefit from low-intensity treatments such as hypomethylating agents combined with venetoclax, now considered a frontline standard of care. The use of liposomal chemotherapy (CPX-351), measurable residual disease (MRD) monitoring, and maintenance therapy further refine post-remission strategies. Emerging therapies, including menin inhibitors, antibody–drug conjugates, and immunotherapies like CAR-T cells and vaccines, offer additional options, especially in relapsed/refractory settings. This comprehensive review outlines the current landscape and future directions in AML therapy, emphasizing the transition toward individualized, mutation-driven treatment strategies. Full article

This field study presents an elimination strategy for African Swine Fever Virus (ASFV), particularly low-virulence genotype II strains, in a large-scale breeding herd in China. Since its introduction to China in 2018, ASFV has spread rapidly, causing significant economic losses. The emergence of low-virulence strains in 2020 further complicated the efforts against this virus. We describe a case study on a farm with 6000 sows in eastern China. Upon ASFV detection, pig movements were ceased immediately, strict biosecurity protocols were implemented, and an epidemiological investigation was conducted to identify high-risk zones. Pigs that tested positive or within high-risk zones were culled, followed by extensive disinfection of exposed areas and whole-herd PCR screening. Injection of a foot and mouth disease vaccine was utilized to stimulate virus excretion of latent infections for better detection. Four rounds of whole-herd tests were conducted to confirm the elimination of ASFV. This case study highlights the importance of timely monitoring, rapid culling, thorough disinfection, and enhanced biosecurity as an effort to control ASF outbreaks in a low-impact and more cost-efficient manner, so called “tooth extraction.” Full article

Despite improved diagnostic and treatment protocols, cancer remains a leading cause of morbidity and mortality globally. There are increasing rates of certain cancer types, including the highly drug-resistant colorectal cancer, in younger population cohorts. Therapeutic advances in oncology have led to the application of immunotherapy-based agents, including checkpoint inhibitors, antibodies, and adoptive cell therapies. Such immunotherapy approaches are greatly hindered by the tumour microenvironment and lack of specificity. Therapeutic vaccines are an innovative and rapidly advancing area of oncology, having potential for application as mono- and combined therapy in clinical settings, offering long term efficacy against disease recurrence. Advances in vaccine production using gene editing and bioprocessing techniques allows for novel vaccine types, including protein-based subunit vaccines, virus-like particle vaccines, and viral vector- and nucleic acid-based (RNA and DNA) vaccines. Cancer vaccines are designed to deliver specific tumour antigens, which activate anti-cancer cytotoxic T cells and helper T cells to produce immune memory, providing long term anti-cancer action. When coupled with advances in machine learning and artificial intelligence, anti-cancer vaccines may revolutionise oncology protocols and improve patient prognosis. This review aims to discuss current immunotherapy options in cancer treatment and recent advances in anti-cancer vaccine modalities. Full article

Streptococcus pneumoniae remains a leading cause of invasive diseases, particularly affecting young children and the elderly. Currently, two main types of pneumococcal vaccines are commercially available: polysaccharide vaccine (PPSV23) and conjugate vaccines (e.g., PCV20). Of over 100 identified pneumococcal serotypes, vaccines targeting 24 serotypes covered by PPSV23 and PCV20 (19 serotypes overlap between the two vaccines) have been developed, with serotype distribution varying by geography, age, and time. The immune response to pneumococcal vaccines differs across serotypes, vaccine types (polysaccharide vs. conjugate), and host factors. Quantitative methods for antibody assessment—particularly newer high-throughput assays—have emerged since 2000 to address limitations in conventional approaches. However, these methods have not been comprehensively reviewed. This scoping review aimed to systematically map the existing literature on quantitative methods used to assess antibody responses to pneumococcal vaccines. Specific objectives included the following: 1. summarizing conventional and novel quantitative immunoassays; 2. evaluating the current state of validation and application of these methods; 3. identifying knowledge gaps and methodological challenges. We followed the PRISMA-ScR guidelines. We included the following: 1. peer-reviewed, open-access papers related to immunoassays used for pneumococcal antibody assessment; 2. articles written in English; 3. Studies published between 2000 and 2023. We excluded the following: 4. studies focusing on other pathogens, employing different analytical methods, or using animal models. Articles meeting the eligibility criteria were primarily retrieved from PubMed and Scopus. If free full-text versions were unavailable there, Google Scholar or the original journal databases were consulted. All references were exported to EndNote 20 for further management. At the beginning of the review, a data-charting form was developed based on prior studies and commonly addressed themes. Additional charts were created to accommodate newly identified variables during the review. All charting tools were reviewed and finalized through discussion among all research team members. The included studies were classified into five thematic groups: 1. general descriptions of quantitative assessment methods, 2. assay development and validation, 3. comparative studies, 4. technical details of assay development, 5. interpretation of assay application findings. Of 1469 articles from PubMed and 2946 articles from Scopus initially identified, 55 articles met the inclusion criteria. The earliest methods included radioimmunoassays, later replaced by WHO-standardized ELISA. While ELISA remains the gold standard, it is limited by labor, cost, and throughput. Multiplex immunoassays (MIAs), including Luminex-based platforms, have demonstrated advantages in efficiency and scalability. However, many MIAs did not initially meet WHO validation criteria. More recent assays show an improved performance, yet interlaboratory variability and lack of standardized protective thresholds remain major limitations. This review provides the first comprehensive mapping of quantitative antibody assessment methods for pneumococcal vaccines. Although ELISA continues to serve as the benchmark, MIAs represent a promising next-generation approach. Continued efforts are needed to harmonize assay validation protocols and establish global standards for protective thresholds, which will enhance the reliability of vaccine efficacy monitoring across diverse populations. Full article

Background/Objectives: Multidisciplinary approaches spanning the physical, cognitive, and social domains of geriatric evaluation are essential to promote functional well-being and reduce the aversive consequences of aging. The main objective of the pilot study, “Multidomain Interventions to improve the COgnitive and fUNctional well-being of elderly individuals in residential sTructures” (I-COUNT), is to assess the feasibility of a 6-month multidomain intervention performed on older adults in Long-Term Care Facilities (LTCFs), compared with a group of residents following a traditional care approach. Methods: The intervention will involve two LTCFs in Italy and will include physical exercise and cognitive training, administered and monitored using wearable technologies, a nutritional program based on the Mediterranean diet enriched with selected functional foods, and the administration of the vaccinations recommended in the national vaccination plan. The I-COUNT study will assess the feasibility and acceptability of the defined protocol and provide information to determine the sample size for a definitive study. In relation to the potential health impact of multidomain interventions on older people living in LTCFs, the primary outcome will consider the change in microbiota composition assessed 3 months after the start of interventions, while secondary outcomes will include the evaluation of changes in selected biomarkers, physical performance, psychological health, cognitive functioning, and nutritional status at 6- and 9-month follow-up points. Conclusions: The I-COUNT study will allow us to assess the feasibility of delivering a multidomain intervention on elderly people. Exploratory findings on potential health effect will support the development of a larger-scale randomized controlled trial. Trial registration number: ClinicalTrials.gov ID NCT06820710. Full article