Search Results (3,274)

Background/Objectives: Epithelial ovarian cancer (EOC) remains a gynecologic malignancy with a poor prognosis, with a 5-year survival of approximately 29% in advanced-stage disease. Despite cytoreductive surgery and platinum- and taxane-based chemotherapy, most patients relapse within 2 years. Major therapeutic barriers include chemoresistance, molecular heterogeneity, and an immunosuppressive peritoneal microenvironment. This review summarizes emerging therapeutic strategies for EOC, their mechanisms of action, and their potential to overcome treatment resistance. Methods: PubMed/MEDLINE was searched for preclinical studies, phase I–III clinical trials, systematic reviews, and meta-analyses addressing novel ovarian cancer therapies and resistance mechanisms. Results: The review covers molecularly targeted therapies, immunotherapies, metabolic and epigenetic approaches, cellular and gene therapies, targeted drug-delivery systems, and locoregional and physical modalities. Strategies include PARP inhibitors, antiangiogenic agents, antibody–drug conjugates, pathway inhibitors, immune checkpoint inhibitors, cancer vaccines, adoptive cell therapies, metabolic and epigenetic modulators, CAR-T, CAR-NK, CRISPR/Cas9, HIPEC, PIPAC, ablation, photodynamic therapy, and sonodynamic therapy. Conclusions: The clinical maturity of these approaches varies substantially. PARP inhibitors, antiangiogenic agents, selected antibody–drug conjugates, MAPK-directed therapy in LGSOC, and HIPEC in selected settings have the strongest clinical support. Most immune combinations, metabolic and epigenetic therapies, adoptive cell therapies, gene-editing approaches, and novel delivery or physical modalities remain early clinical or predominantly preclinical. Progress will depend on biomarker-guided patient selection, reassessment of evolving resistance mechanisms, and rational treatment sequencing and combinations. Full article

Non-communicable diseases (NCDs), including cancer, cardiovascular, neurodegenerative, autoimmune, and allergic diseases, account for a significant amount of global morbidity and mortality. Chronic viral infections have not been recognized as NCDs, despite the availability of several therapeutic vaccination strategies against oncogenic viruses, such as the hepatitis B virus (HBV) and the human papillomavirus (HPV). Indeed, chronic viral infection leads to the development and progression of malignancies directly linked to the viruses. These considerations support a connection between NCDs, infectious diseases, and therapeutic vaccination. Recent advances in technology have paved the way to the use of vaccines beyond the prevention of infectious diseases, heralding innovative therapeutic and preventative strategies for a variety of chronic NCDs. Here we will review the state of the art of personalized vaccine strategies for NCDs, with an emphasis on the diverse technological platforms used to develop them, including mRNA and DNA vaccines, viral vectors, dendritic cell-based vaccines, nanoparticle delivery systems, and next-generation adjuvants. The review intends to make the case for personalized and antigen-specific vaccination strategies as a compelling option for precision immunotherapy primarily in oncology, where neoantigen-based vaccines are being developed. In addition, we will also review tolerogenic vaccination strategies, vaccination strategies targeting pathological proteins and pathways in neurodegenerative and cardiovascular diseases, and vaccine-based treatment of chronic viral infections. Current evidence about vaccines suggests that several ways are available to induce an immune response or create tolerance to a disease, and possibly altering its course instead of simply controlling the symptoms. However, many challenges are still to be overcome, including disease variability, how to identify appropriate target antigens, the complexity of manufacturing process, long-term safety, and integration with already established treatments. By virtue of the convergence of multiple fields—immunology, genomics, bioinformatics, and new delivery systems—precision vaccinology is gaining momentum. Thus, it is envisaged that personalized vaccines will be an increasingly essential component of future preventive and therapeutic approaches for non-communicable diseases. Full article

Filoviruses cause highly lethal infectious diseases with hemorrhagic symptoms and extremely high fatality rate (up to 90%). Although two vaccines against Ebola virus (EBOV) are licensed for application in endemic areas, vaccines against other filoviruses (SUDV, BDBV, MARV) are still at pre-clinical or clinical stages. The development of vaccines requires protective efficacy studies using animal models of infection. However, animal studies using wild-type filoviruses require maximum biosafety level (BSL-4), which hinders filoviral vaccine advancement. In this study, we developed a surrogate animal model of EBOV-, SUDV-, BDBV- and MARV- GP-mediated entry using Ifnar1-knockout (-/-) mice and recombinant vesicular stomatitis viruses (rVSVs), carrying a genetic sequence of filoviral glycoprotein (GP) and pseudotyped with correspondent GP. We showed that rVSV-EBOV-GP was 100% lethal for Ifnar1(-/-) mice after inoculation by multiple routes, and its active propagation was within 24 h post-infection. We performed dose-dependent lethality assessment in small groups to estimate median lethal doses for rVSV-EBOV-GP, rVSV-SUDV-GP, rVSV-BDBV-GP, rVSV-MARV-GP in Ifnar1-knockout mice and showed high viral load in liver and immune cell reservoirs. The developed models contribute to safe and effective research of filoviral vaccines and therapeutic antibodies under BSL-2 conditions. Full article

Trained immunity refers to the functional reprogramming of innate immune cells—such as monocytes, macrophages, and natural killer cells—those results in a modulated, and often heightened, response to secondary stimuli. This phenomenon challenges the traditional view that immunological memory is restricted to the adaptive immune system and has emerged as a concept linking host defense, vaccination, and inflammatory disease. This review synthesizes current evidence on the molecular basis of trained immunity, including chromatin remodeling, histone modifications, and metabolic rewiring, and examines how bacteria, viruses, and fungi induce, evade, or exploit these programs. The dual contribution of trained immunity to protective host defense and to immunopathology is discussed, along with its implications for vaccine design—including heterologous protection reported after BCG vaccination—and its potential as a therapeutic target in infectious and inflammatory disease. Key gaps, particularly the duration and reversibility of the trained state, the distinction between trained immunity and related processes such as innate tolerance, and the need for validated biomarkers, are highlighted, together with priorities for future translational research. Full article

Aquaculture has become the leading source of global aquatic food production, and its continued expansion has been accompanied by an increasing burden of bacterial diseases. Aeromonas spp. are among the most damaging bacterial pathogens in aquaculture and are recognised reservoirs of antimicrobial resistance within a One Health framework. Although bacteriophages have been investigated against numerous aquaculture pathogens, evidence relating to Aeromonas-targeting phages remains dispersed across studies. This integrative review synthesises research published between 1981 and 2026 on bacteriophages targeting Aeromonas spp. and examines the development of the field from early isolation studies to current therapeutic and translational applications. Studies were identified through structured searches of PubMed, Web of Science and Scopus and analysed for phage isolation, genomic characterisation, therapeutic efficacy, delivery strategies and phage-derived applications. Comparison of findings across studies reveals several consistent patterns. Phage cocktails generally provided broader antibacterial activity and reduced the emergence of antimicrobial-resistant strains compared with single-phage treatments. Preventive applications consistently produced higher survival rates than treatments applied after infection, while whole-genome sequencing has become a routine component of candidate phage evaluation. Recent studies have expanded the scope of phage-based interventions beyond intact virions to include phage-derived endolysins, oral delivery systems and phage lysate-based vaccine approaches. The evidence shows that bacteriophages can reduce mortality, suppress bacterial infections and improve survival across diverse aquaculture species affected by Aeromonas spp. Phage resistance, large-scale implementation and regulatory harmonisation remain important challenges, supporting further development of phage-based disease management in aquaculture. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) and other systemic therapies can extend the survival of many patients with advanced melanoma, renewing interest in complementary strategies for unresectable or metastatic disease. Therapeutic cancer vaccines represent a possible approach. Recent evidence suggests commercially available mRNA vaccines can sensitize tumors to ICIs, challenging prior assumptions about neoantigen presentation. Despite renewed public interest in personalized cancer vaccine development, the proliferation of narrative and scoping reviews has not been matched by systematic mechanistic synthesis—platforms investigated across the 2010s and 2020s have not been rigorously compared within a single article. Accordingly, this review focuses on major vaccine platforms and proposes a comparative framework for understanding therapeutic melanoma vaccine development and immunologic rationale. Methods: Melanoma vaccine clinical trials listed on ClinicalTrials.gov were identified from 2010 to 2025. Eligible studies were screened and included in a qualitative review evaluating trial characteristics, vaccine platforms, study design, and reported outcomes. Results: There is one active Phase III clinical trial for melanoma vaccines in the US. Key principles of melanoma vaccinology include adjuvant, antigen, and delivery platform selection. From 2010 to 2025, four vaccine candidates advanced to Phase III trials, two provided Phase III results for peer review, one trial is ongoing, and no vaccines have been FDA-approved. Inconsistent reporting of outcomes and a lack of published results limited comparability across studies, precluding formal meta-analysis. Conclusions: Therapeutic melanoma vaccine options remain limited by translational challenges in study design and reporting gaps. This review synthesizes contemporary clinical trial activity and immunologic principles to inform future research. Full article

Dengue virus (DENV) remains a major global public health challenge, driven by the expanding distribution of Aedes vectors, rapid urbanization, and increasing climate variability. This review aimed to synthesize current evidence on dengue transmission dynamics, immunopathogenesis, molecular epidemiology, diagnostic and therapeutic advances, vaccine development, and the influence of climatic factors on disease patterns. A comprehensive search of major electronic databases was conducted to identify relevant literature, followed by a qualitative synthesis of the evidence. The evidence highlights complex transmission cycles involving Aedes aegypti and Aedes albopictus, with transmission strongly influenced by temperature, humidity, rainfall, and extreme climate events. Advances in immunopathogenesis research have improved understanding of mechanisms associated with severe disease, including antibody-dependent enhancement and dysregulated inflammatory responses. Diagnostic innovations, such as reverse transcription polymerase chain reaction (RT-PCR), NS1 antigen detection, and point-of-care technologies, have enhanced case identification, while prevention strategies increasingly incorporate integrated vector management, digital surveillance systems, and emerging vaccines. Integrating epidemiological, molecular, and climatic information may strengthen early warning systems, improve outbreak prediction, and support more effective dengue prevention and control strategies. Full article

Bacterial extracellular vesicles (BEVs) are nano-sized lipid bilayer particles secreted by bacteria, capable of carrying various proteins, lipids, nucleic acids, and pathogen-associated molecular patterns (PAMPs). The biosynthetic pathway of BEVs determines their load components, physicochemical properties, and different biological activities. Increasing evidence indicates that BEVs play an important role in mediating host immune responses and the dynamic regulation of bacterial biofilms. Additionally, BEVs may serve as a molecular bridge between the two. BEVs derived from pathogens can trigger pro-inflammatory cascades, assist bacteria in immune evasion, and further accelerate the maturation of biofilms, forming a vicious cycle of persistent infection and inflammatory damage. In contrast, BEVs derived from probiotics can maintain host immune homeostasis and exert direct anti-biofilm and synergistic antibacterial effects, thereby breaking the pathological cycle. However, significant methodological research bottlenecks have greatly hindered the comparability and clinical translation of BEVs research. This article systematically summarizes the classification of BEVs and their biosynthetic mechanisms, compares the differential effects of BEVs from pathogenic bacteria and probiotic bacteria on immunity, clarifies the dual regulatory role of BEVs throughout the life cycle of biofilms, and highlights the bridging function of BEVs in the immune–biofilm interaction. Additionally, this article also discusses the current development of BEVs in clinical translation applications, such as vaccine development, antibiotic delivery, and mucosal inflammation intervention, and outlines the key industrial and clinical challenges faced in the future development of BEVs-based therapeutic approaches. Full article

The discovery of neoantigens and their application in cancer vaccines have brought about a paradigm shift in cancer immunotherapy, similar to the way in which immune checkpoint inhibitors redefined therapeutic strategies for cancer treatment. Early neoantigen vaccine approaches primarily focused on eliciting HLA class I-restricted CD8⁺ cytotoxic T lymphocyte (CTL) responses, whereas it has become clear that such strategies alone may be insufficient to establish durable and effective antitumor immunity. Increasing attention has therefore shifted toward HLA class II-restricted neoantigens (“helper neoantigens”) that activate tumor-specific CD4⁺ helper T cells. Recent studies have revealed that neoantigen-reactive CD4⁺ helper T cells play a central role in coordinating antitumor immune responses through dendritic cell licensing, thereby sustaining CD8⁺ CTL function, preventing T-cell exhaustion, and promoting the generation of long-lived memory T cells. These findings have highlighted the pivotal role of helper neoantigens in shaping vaccine efficacy. In this review, we discuss the mechanistic basis underlying the contribution of helper neoantigens to tumor immunity and highlight recent advances in the real-world application of helper neoantigen-based vaccine strategies. Full article

Oral delivery of bioactive compounds in veterinary medicine offers important opportunities to improve animal health, productivity, and welfare, but its effectiveness is often limited by species-specific gastrointestinal physiology. This review aims to provide a comprehensive overview of microencapsulation strategies for oral veterinary delivery, focusing on species-specific gastrointestinal barriers and the formulation approaches developed to overcome them. Monogastric and ruminant animals present distinct gastrointestinal environments that compromise the stability, bioavailability, and therapeutic performance of orally administered compounds. In monogastrics, gastric acidity, digestive enzymes, gastrointestinal transit, and microbiota-mediated interactions represent major barriers, whereas in ruminants, ruminal fermentation, prolonged retention, and physicochemical conditions may cause premature degradation of bioactive compounds. These barriers significantly hinder the successful use of probiotics, enzymes, essential oils, nutrients, vaccines, and veterinary drugs. However, microencapsulation has emerged as a promising solution, providing a protective barrier that improves compound stability, enhances gastrointestinal survival, and enables controlled or site-specific release. By preserving bioactivity and modulating release kinetics, microencapsulation contributes to improved delivery efficiency and functional performance. A distinctive feature of this review is the integration of species-specific gastrointestinal physiology with microencapsulation technologies to provide a rational framework for designing oral delivery systems in veterinary medicine, rather than focusing solely on individual encapsulation technologies. Current challenges related to material selection, formulation optimisation, and industrial scalability are discussed. Overall, this review highlights that integrating gastrointestinal physiology with advanced microencapsulation technologies is essential for developing effective, targeted, and sustainable oral delivery systems, ultimately supporting improved animal health, productivity, and welfare. Full article

Influenza remains a significant national health security threat, particularly for vulnerable populations, as existing control measures do not fully mitigate its impact. This gap in protection is especially pronounced early in a pandemic when a well-matched vaccine may not yet be available, as well as in populations unable to mount an optimal vaccine response. Clinical studies support pre-exposure prophylaxis (PrEP) therapeutics as a promising complementary strategy to reduce influenza transmission and disease severity, potentially easing the strain on healthcare systems during outbreaks. This manuscript outlines the Biomedical Advanced Research and Development Authority’s (BARDA’s) target product profile (TPP) for a long-acting influenza PrEP product, reviews the current development landscape, and models the potential impact of early PrEP product deployment using agent-based modeling in a synthetic population of 19.5 million people across pandemic scenarios resembling the 1918, 1968, and 2009 influenza pandemics. Simulations showed that early deployment of a 70%–effective PrEP reduced cumulative and peak infections, delayed the epidemic peak, and provided the greatest benefit in less transmissible pandemics; at 40–50% coverage, PrEP fully mitigated a 2009-like pandemic and substantially reduced transmission in 1918- and 1968-like scenarios. The TPP defines key characteristics of an effective PrEP option for seasonal and pandemic influenza that (1) demonstrates a strong safety and tolerability profile across all populations; (2) targets a direct-acting antiviral mechanism of action; (3) reduces the relative risk of symptomatic influenza infection by at least 70% in an unvaccinated population and (4) provides single-dose, season-long protection to optimize patient adherence. In this context, integrating PrEP into influenza prevention strategies could improve control of virus spread, strengthen protection for high-risk groups, and significantly reduce the overall public health impact of seasonal and pandemic influenza. Full article

Messenger RNA (mRNA) entered clinical medicine through vaccines, where the innate immune reactivity that complicates protein therapeutics acts as a built-in adjuvant. The success of the coronavirus disease 2019 (COVID-19) mRNA vaccines inspired an expansive vision of an mRNA 2.0 era extending the modality to rare and common diseases, with delivery framed as the principal challenge. This review accepts much of that vision but argues it rests on an unstated assumption: that all protein therapeutics form a single pharmacological class. They do not. We propose a taxonomy, the Dose–Response Architecture Classification, separating two classes. Exposure-controlled therapeutics require a specific quantity of active protein on a defined regimen, as outcomes depend on reproducible exposure; examples include insulin, erythropoietin, growth hormone, coagulation factors, and narrow-therapeutic-index biologics. Threshold-response therapeutics depend on surpassing a functional threshold rather than maintaining a precise concentration; these include vaccines, many enzyme-replacement therapies, genome editing, receptor-saturating antibodies, and immune-cell reprogramming. Because an mRNA drug is dosed as an instruction, and a single message is translated into a variable number of proteins through a multiplicative, stochastic intracellular chain, the dose-to-effect relationship is inherently variable. Our central, deliberately falsifiable proposition is that mRNA is suitable for threshold-response therapeutics but unsuitable for exposure-controlled therapeutics unless a construct or delivery system demonstrates validated post-delivery output control within predefined pharmacokinetic and pharmacodynamic limits. This is a pharmacological boundary, not a delivery obstacle. We conclude that the greatest advances in mRNA 2.0 will come not from delivery alone but from disciplined indication triage by class. Full article

Introduction: Storytelling is gaining interest as a potentially useful research and communication approach in health. However, there remains a huge gap in synthesized evidence in relation to its use in vaccination. We set out to map existing evidence on the use of storytelling in vaccination practice. Methods: This review was conducted in accordance with Joanna Briggs Institute methodology and PRISMA-ScR guidelines. Databases were searched for eligible studies using search strings in PubMed, Scopus, Academic Search Premier, Africa Wide Information, PsycINFO, ERIC, Cochrane Library, Web of Science Core Collection, and SciELO Citation Index via Web of Science. The gray literature was searched on Primo and Google Scholar. References from other sources were identified through a manual search using Google. Identified citations were uploaded into Covidence for screening and data extraction. Qualitative content analysis was used to summarize data in conceptual categories, including frequency counts. Results: Overall, 6236 studies were identified and imported into Covidence. Following removal of duplicates, 3804 studies were screened for title and abstract. 386 studies met eligibility criteria for full-text screening, which led to 110 included studies. Storytelling was used in immunization between 1997 and 2025 as a communication intervention (96/110 studies), research method (12/110 studies), and therapeutic approach (3/110 studies). Most studies originated from North America (67/110 studies), while six originated from Africa. Two-thirds of included studies (64/110 studies) were randomized controlled trials. Among the 62 studies reporting vaccine-related outcomes, 80.6% (50/62 studies) reported changes in one or more vaccine-related outcomes following exposure to storytelling interventions. The trustworthiness of these outcome findings is unknown. Reported changes were more frequently observed for cognitive, affective, and intentional outcomes than for behavioral outcomes such as vaccine uptake. Again, these findings have not been subject to critical appraisal. Conclusions: Storytelling is emerging as an adaptable approach with potential for addressing contextual vaccine challenges. Although several studies reported changes in cognitive, affective, and intentional outcomes, this scoping review cannot ascertain whether these changes were attributed to storytelling itself. Full article

Acinetobacter baumannii, a Gram-negative opportunistic bacterium in the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, A. baumannii, Pseudomonas aeruginosa and Enterobacter spp.), has emerged as a leading cause of nosocomial infections worldwide. It is known to possess diverse virulence traits and antimicrobial resistance, making it a critical priority pathogen on the World Health Organization’s 2024 Bacterial Priority Pathogens List. Carbapenem-resistant A. baumannii (CRAB) is currently endemic across several continents, with global carbapenem resistance exceeding 70% in healthcare settings and multidrug-resistant infections being associated with alarming mortality rates. This review comprehensively discusses the molecular underpinnings of A. baumannii pathogenesis and virulence, detailing the array of factors coordinated by complex regulatory networks. The convergence of this pathogen’s virulence and antimicrobial resistance traits, resulting in multidrug resistance, leaves clinicians with only a handful of therapeutic options. The review also discusses upcoming therapeutic strategies, including phage therapy, antimicrobial peptides, monoclonal antibodies, photodynamic therapy, and vaccine candidates in the pipeline. While emerging therapeutics show promise, several challenges remain, and integrated approaches are warranted to efficiently combat A. baumannii’s virulence and resistance armamentarium. Full article

Therapeutic cancer vaccines are designed to initiate tumor-specific immunity, yet their clinical success depends not only on antigen selection but also on the capacity to overcome the profoundly suppressive tumor microenvironment. Within tumors, abnormal vasculature, hypoxia, nutrient competition, acidic pH, and suppressive myeloid and stromal cells collectively constrain antigen presentation, T-cell priming, trafficking, and effector function, often converting otherwise immunogenic vaccination into an ineffective immune stimulus. Recent advances in neoantigen discovery, dendritic cell engineering, and nucleic acid-based vaccine platforms have improved the precision of antigen delivery, but these gains remain insufficient unless vaccine-induced responses can be sustained and executed within the hostile metabolic and immunologic landscape of the tumor niche. In this context, the tumor microenvironment is not merely a barrier to be overcome, but an active determinant of vaccine outcome that shapes immune editing, promotes exhaustion, and limits intratumoral expansion of cytotoxic lymphocytes. Accordingly, the most promising therapeutic strategies now combine vaccination with checkpoint blockade, radiotherapy, stromal remodeling, or metabolic reprogramming to recondition the tumor ecosystem and permit productive antitumor immunity. Here, we discuss how tumor microenvironmental constraints govern vaccine performance, review emerging platform technologies, and outline combinatorial strategies aimed at converting immune priming into durable tumor control. Full article