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Search Results (918)

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Keywords = vaccination and treatment controls

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23 pages, 5970 KiB  
Review
Practical Review on Aetio-Pathogenesis and Symptoms in Pigs Affected by Clinical and Subclinical Oedema Disease and the Use of Commercial Vaccines Under Field Conditions
by Juan Hernandez-Garcia, Isaac Ballarà Rodriguez, Ramon Jordà Casadevall, Sergi Bruguera, David Llopart and Emili Barba-Vidal
Animals 2025, 15(15), 2275; https://doi.org/10.3390/ani15152275 - 4 Aug 2025
Abstract
The impact of Oedema Disease produced by Shiga toxigenic Escherichia coli (STEC) in swine is increasing in some production countries due to increasing limitations on treatment with antimicrobials and zinc oxide, either because of the increased prevalence of multi-resistant strains or because of [...] Read more.
The impact of Oedema Disease produced by Shiga toxigenic Escherichia coli (STEC) in swine is increasing in some production countries due to increasing limitations on treatment with antimicrobials and zinc oxide, either because of the increased prevalence of multi-resistant strains or because of legal restrictions. The main pathological effect of Shiga toxin 2e is represented by damage to the endothelial cells of the blood vessel walls, leading to liquid extravasation and oedema formation in multiple tissues. These oedemas are generally easily identifiable in acute clinical cases. However, disease caused by Shiga toxin can occur without any externally visible oedema in the pigs, as observed in the subclinical presentation of Oedema Disease. It also causes productive losses, so it is important to identify and/or diagnose cases to set up control measures in order to optimize production and health. This article includes a comprehensive review of lesions and signs caused by Shiga toxin toxicosis in pigs, as well as other insights about the aetiology and epidemiology of STEC in pigs, and the effect of Shiga toxin recombinant toxoid vaccines in reducing these clinical and subclinical signs under field conditions. Full article
(This article belongs to the Section Pigs)
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21 pages, 4740 KiB  
Article
Mosquito Exosomal Tetraspanin CD151 Facilitates Flaviviral Transmission and Interacts with ZIKV and DENV2 Viral Proteins
by Durga Neupane, Md Bayzid, Girish Neelakanta and Hameeda Sultana
Int. J. Mol. Sci. 2025, 26(15), 7394; https://doi.org/10.3390/ijms26157394 (registering DOI) - 31 Jul 2025
Viewed by 193
Abstract
The expanding distribution and geographic range of mosquitoes have potentially contributed to increased flaviviral dissemination and transmission. Despite the growing burden of flaviviral infections, there are no effective antiviral treatments or vaccines, highlighting the need for novel therapeutic targets. Tetraspanins, a superfamily of [...] Read more.
The expanding distribution and geographic range of mosquitoes have potentially contributed to increased flaviviral dissemination and transmission. Despite the growing burden of flaviviral infections, there are no effective antiviral treatments or vaccines, highlighting the need for novel therapeutic targets. Tetraspanins, a superfamily of transmembrane domain glycoproteins involved in cellular organization, signaling, and protein–protein interactions have been recognized as potential mediators of flaviviral infection and transmission. While their roles in vertebrate hosts have been explored, their involvement in flaviviral replication and dissemination within medically important vectors remains poorly understood. In this study, we investigated the role of arthropod tetraspanins in mosquito cells and extracellular vesicles (EVs) derived from cells infected with Zika virus (ZIKV) and dengue virus (serotype 2; DENV2). Among several of the tetraspanins analyzed, only CD151 was significantly upregulated in both mosquito cells and in EVs derived from ZIKV/DENV2-infected cells. RNAi-mediated silencing of CD151 led to a marked reduction in viral burden, suggesting its crucial role in flavivirus replication. Inhibition of EV biogenesis using GW4869 further demonstrated that EV-mediated viral transmission contributes to flavivirus propagation. Additionally, co-immunoprecipitation and immunofluorescence analyses revealed direct interactions between CD151 and ZIKV NS2B and DENV2 capsid proteins. Overall, our findings highlight the functional importance of mosquito CD151 in the replication and transmission of ZIKV and DENV2. This study provides new insights into the molecular mechanisms of flaviviral infection in mosquitoes and suggests that targeting vector tetraspanins may offer a potential approach to controlling mosquito-borne flaviviruses. Full article
(This article belongs to the Special Issue Advanced Perspectives on Virus–Host Interactions)
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16 pages, 776 KiB  
Article
Safety and Toxicology Profile of TT-6-AmHap Heroin Conjugate Vaccine
by Essie Komla, Erwin G. Abucayon, C. Steven Godin, Agnieszka Sulima, Arthur E. Jacobson, Kenner C. Rice and Gary R. Matyas
Vaccines 2025, 13(8), 792; https://doi.org/10.3390/vaccines13080792 - 26 Jul 2025
Viewed by 389
Abstract
Background/Objectives: Opioid use disorder (OUD) remains a severe health problem globally, resulting in substantial social and economic challenges. While existing medications for managing OUD are proven to be effective, they also present certain challenges. A vaccine offers a promising therapeutic strategy to [...] Read more.
Background/Objectives: Opioid use disorder (OUD) remains a severe health problem globally, resulting in substantial social and economic challenges. While existing medications for managing OUD are proven to be effective, they also present certain challenges. A vaccine offers a promising therapeutic strategy to combat OUD and potentially reduce the risk of overdose death. The TT-6-AmHap heroin conjugate vaccine has effectively reduced heroin-induced pharmacological effects in behavioral assays as well as demonstrated the induction of high titer and high affinity antibody responses in mice and rats. In this GLP study conducted in rabbits, the potential local and systemic toxicity of the TT-6-AmHap heroin vaccine in combination with or without adjuvants ALF43 and Alhydrogel® (ALFA) was investigated. Methods: Male and female New Zealand White rabbits were administered with vaccines or a saline control intramuscularly at two-week intervals over a 57-day study period. The presence, persistence or reversibility of any toxic effects of the vaccine was determined over a four-week recovery period. Results: Administration of TT-6-AmHap with or without the adjuvants induced high antibody-specific IgG in treatment groups compared to the controls. The study found no TT-6-AmHap-related effects on mortality, physical examinations, dermal Draize observations, body weights, body weight changes, food consumption, ophthalmology, clinical pathology (hematology, coagulation, clinical chemistry, and urinalysis), macroscopic pathology, or organ weights. Conclusions: Under the conditions of this study, these results demonstrate that the TT-6-AmHap vaccine with or without adjuvants was well tolerated, immunogenic, and the effects were not considered adverse in both male and female rabbits. Full article
(This article belongs to the Section Vaccines and Public Health)
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14 pages, 2675 KiB  
Article
Development of a Clostridium Perfringens Challenge Model in Broiler Chickens to Evaluate the Effects of Feed Additives
by Anna Kollár, Kinga Selymes, Gergely Tóth, Sándor Szekeres, Péter Ferenc Dobra, Krisztina Bárdos, László Ózsvári, Zsófia Bata, Viviána Molnár-Nagy and Miklós Tenk
Pathogens 2025, 14(7), 707; https://doi.org/10.3390/pathogens14070707 - 17 Jul 2025
Viewed by 381
Abstract
Necrotic enteritis, caused by Clostridium perfringens (C. perfringens) is a disease present worldwide and causes major economic losses. The re-emergence of the disease, in recent years, is mainly due to the ban of the usage of antibiotics as growth promoters in [...] Read more.
Necrotic enteritis, caused by Clostridium perfringens (C. perfringens) is a disease present worldwide and causes major economic losses. The re-emergence of the disease, in recent years, is mainly due to the ban of the usage of antibiotics as growth promoters in the EU. The aim of this study was to establish a reliable, robust challenge model. Ross hybrid broilers were divided into randomized groups: a positive and a negative control group, a group receiving antibiotic treatment and three groups fed with assorted feed supplements, all receiving the same basal diet. The birds in the treatment groups were vaccinated twice using a 10-times dose of an Infectious Bursitis live vaccine and the animals were challenged four times with a NetB toxin producing C. perfringens strain. The presence of clinical signs and body weight gain were monitored. At the end of the study necropsy was performed and the gut lesions were scored. During the experiment, clinical signs were absent in the negative control group and in the antibiotic treated group. The other animals displayed diarrhea and feather loss. These symptoms were the most pronounced in the positive control group. The gut lesion scores showed significant differences between the negative and positive control groups, with the former scoring the lowest. Based on these results, the challenge model establishment was successful and in this setup the assessment of the potency of feed additives is also possible. Full article
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29 pages, 7767 KiB  
Article
Therapeutic Efficacy of CD34-Derived Allogeneic Dendritic Cells Engineered to Express CD93, CD40L, and CXCL13 in Humanized Mouse Models of Pancreatic Cancer
by Sara Huerta-Yepez, Jose D. Gonzalez, Neha Sheik, Senay Beraki, Elango Kathirvel, Ariel Rodriguez-Frandsen, Po-Chun Chen, Tiran Sargsyan, Saleemulla Mahammad, Mark R. Dybul, Lu Chen, Francois Binette and Anahid Jewett
Vaccines 2025, 13(7), 749; https://doi.org/10.3390/vaccines13070749 - 12 Jul 2025
Viewed by 866
Abstract
Background/Objectives: Pancreatic cancer remains the fourth leading cause of cancer-related deaths. While peripheral blood-derived mature dendritic cell (mDC) vaccines have shown potential in eliciting anti-tumor immune responses, clinical efficacy has been limited. This study aimed to enhance the potency and scalability of [...] Read more.
Background/Objectives: Pancreatic cancer remains the fourth leading cause of cancer-related deaths. While peripheral blood-derived mature dendritic cell (mDC) vaccines have shown potential in eliciting anti-tumor immune responses, clinical efficacy has been limited. This study aimed to enhance the potency and scalability of DC-based immunotherapy by developing an allogeneic DC platform derived from CD34+ hematopoietic stem cells (HSCs), genetically engineered to overexpress CD93, CD40L, and CXCL13, followed by maturation and tumor antigen pulsing. Methods: Engineered DCs were generated from CD34+ HSCs and matured in vitro after lentiviral transduction of CD93, CD40L, and CXCL13. Tumor lysates were used for antigen pulsing. A scrambled-sequence control DC was used for comparison. In vitro assays were performed to assess T cell activation and tumor cell killing. In vivo efficacy was evaluated using orthotopic pancreatic tumors in BLT and PBMC-humanized NSG mice established with the MiaPaca-2 (MP2) cell line. Results: Engineered DCs significantly enhanced T cell activation and tumor-specific cytotoxicity in vitro compared to control DCs. Antigen pulsing further amplified immune activation. In vivo, treated humanized mice showed increased CD4+, CD8+, and NK cell frequencies in peripheral blood and within tumors, correlating with reduced tumor burden. Conclusions: Our data shows that the antigen-pulsed, engineered DCs have the potency to activate immune cells, which leads to a significant reduction in pancreatic tumors and therefore could potentially provide an effective therapeutic opportunity for the treatment of pancreatic cancer and other solid tumors. Full article
(This article belongs to the Section Vaccination Against Cancer and Chronic Diseases)
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15 pages, 452 KiB  
Systematic Review
The Efficacy of Neoantigen-Loaded Dendritic Cell Vaccine Immunotherapy in Non-Metastatic Gastric Cancer
by Menelaos Papakonstantinou, Paraskevi Chatzikomnitsa, Areti Danai Gkaitatzi, Athanasia Myriskou, Alexandros Giakoustidis, Dimitrios Giakoustidis and Vasileios N. Papadopoulos
Med. Sci. 2025, 13(3), 90; https://doi.org/10.3390/medsci13030090 - 11 Jul 2025
Viewed by 965
Abstract
Introduction: Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Even though surgery and chemotherapy are the mainstay of treatment, immunotherapy, and more specifically anti-tumor vaccination, has gained popularity over the past years due to the lower related toxicity and [...] Read more.
Introduction: Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Even though surgery and chemotherapy are the mainstay of treatment, immunotherapy, and more specifically anti-tumor vaccination, has gained popularity over the past years due to the lower related toxicity and fewer long-term side effects. Dendritic cell (DC) vaccines have been shown to induce tumor specific cytotoxic T-cell (CTL) responses both in vitro and in vivo; however, due to the nature of the disease, resistance to immunotherapy is often developed. Various modifications, such as the implementation of viral vectors, tumor RNA, or even tumor-specific peptides (neoantigens), have been studied as a means to avoid resistance and enhance the effectiveness of the vaccines. In this review, we aim to assess the effects of neoantigen-loaded DC vaccines (naDCVs) on the immune response against gastric cancer cells. Materials and methods: A thorough literature search was conducted on PubMed and clinicaltrials.gov for studies assessing the efficacy of naDCVs against gastric cancer both in vivo and in vitro. The studies were assessed for eligibility by two independent reviewers based on predetermined inclusion and exclusion criteria. The search was completed following the PRISMA guidelines. Results: Eleven studies were included in our systematic review. In five of the studies, the effects of the naDCVs were tested in vitro; in two and in four they were examined both in vitro and in vivo. The in vitro studies showed that the naDCVs resulted in a more robust immune response against the cancer cells in the study groups compared to the control groups. The in vivo studies conducted on mice showed that tumor volume was reduced in the groups treated with the naDCV compared to the untreated groups. What is more, the cytotoxic effect of CTLs against tumor cells was also increased in the vaccine groups. One of the studies was conducted on humans as a phase I study. The results show increased CTL proliferation and cytokine production in the vaccinated group compared to the control, but no difference regarding the tumor size was observed. Conclusions: Neoantigen-loaded DC vaccines can stimulate a strong immune response against specific gastric cancer cell peptides and enhance tumor cell lysis, therefore hindering or even reversing disease progression, offering great potential for the treatment of patients with gastric cancer. Full article
(This article belongs to the Special Issue Feature Papers in Section Cancer and Cancer-Related Diseases)
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26 pages, 888 KiB  
Review
Current Trends in Approaches to Prevent and Control Antimicrobial Resistance in Aquatic Veterinary Medicine
by Dongqing Zhao, Konrad Wojnarowski, Paulina Cholewińska and Dušan Palić
Pathogens 2025, 14(7), 681; https://doi.org/10.3390/pathogens14070681 - 10 Jul 2025
Viewed by 483
Abstract
The growth of aquaculture production in recent years has revealed multiple challenges, including the rise of antimicrobial resistance (AMR) in aquatic animal production, which is currently attracting significant attention from multiple one-health stakeholders. While antibiotics have played a major role in the treatment [...] Read more.
The growth of aquaculture production in recent years has revealed multiple challenges, including the rise of antimicrobial resistance (AMR) in aquatic animal production, which is currently attracting significant attention from multiple one-health stakeholders. While antibiotics have played a major role in the treatment of bacterial infections for almost a century, a major consequence of their use is the increase in AMR, including the emergence of AMR in aquaculture. The AMR phenomenon creates a situation where antibiotic use in one system (e.g., aquaculture) may impact another system (e.g., terrestrial–human). Non-prudent use of antibiotics in aquaculture and animal farming increases the risk of AMR emergence, since bacteria harboring antibiotic resistance genes can cross between compartments such as wastewater or other effluents to aquatic environments, including intensive aquaculture. Transferable antimicrobial resistance gene (AMG) elements (plasmids, transposons, integrons, etc.) have already been detected in varying degrees from pathogenic bacteria that are often causing infections in farmed fish (Aeromonas, Vibrio, Streptococcus, Pseudomonas, Edwardsiella, etc.). This review of current veterinary approaches for the prevention and control of AMR emergence in aquaculture focuses on the feasibility of alternatives to antimicrobials and supplemental treatment applications during on-farm bacterial disease control and prevention. The use of vaccines, bacteriophages, biosurfactants, probiotics, bacteriocins, and antimicrobial peptides is discussed. Full article
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13 pages, 1488 KiB  
Article
Respiratory Syncytial Virus Induces B Cell Activating Factor (BAFF) in Airway Epithelium: A Potential Avenue for Mucosal Vaccine Development
by Wael Alturaiki and Brian Flanagan
Viruses 2025, 17(7), 946; https://doi.org/10.3390/v17070946 - 4 Jul 2025
Viewed by 546
Abstract
Respiratory syncytial virus (RSV) is a major etiological agent of lower respiratory tract infections, particularly among infants and the elderly. Activation of B cells in the mucosa and the production of specific neutralizing antibodies are essential for protective immunity against pulmonary infection. B-cell [...] Read more.
Respiratory syncytial virus (RSV) is a major etiological agent of lower respiratory tract infections, particularly among infants and the elderly. Activation of B cells in the mucosa and the production of specific neutralizing antibodies are essential for protective immunity against pulmonary infection. B-cell activating factor (BAFF) is a critical survival factor for B cells and has been associated with antiviral responses; however, its regulation during RSV infection remains poorly understood. This study examined BAFF regulation in BEAS-2B cells exposed to RSV or IFN-β. The treatments resulted in a progressive increase in gene expression over time, accompanied by higher protein levels. BAFF mRNA peaked at 12 h post-infection and declined by 48 h, coinciding with the release of soluble BAFF protein into the culture supernatant. Pre-treatment with anti-IFN-β antibodies prior to RSV infection reduced both BAFF mRNA and protein levels, indicating that IFN-β plays a regulatory role in BAFF production by airway epithelial cells. Western blot analysis revealed membrane-bound BAFF (~31 kDa) in non-infected cells, with elevated expression at 24 h post-infection. By 48 h, this form was cleaved into a soluble ~17 kDa form, which was detected in the supernatant. Immunostaining further demonstrated reduced surface expression of membrane-bound BAFF in RSV-infected cells compared to uninfected controls, suggesting that RSV infection promotes the cleavage and release of BAFF into the extracellular environment. Additionally, the release of BAFF was not affected by furin convertase inhibition or ER–Golgi transport blockade, indicating a potentially novel cleavage mechanism. Co-culturing BAFF produced by BEAS-2B cells with isolated B cells enhanced B cell viability. Overall, these results indicate that RSV infection stimulates BAFF production in airway epithelial cells through a pathway involving IFN-β, potentially contributing to B cell activation and promoting local antibody-mediated immunity. Understanding this mechanism may offer valuable insights for improving mucosal vaccine strategies and enhancing immunity against respiratory pathogens. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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17 pages, 5007 KiB  
Review
PROTAC-Based Antivirals for Respiratory Viruses: A Novel Approach for Targeted Therapy and Vaccine Development
by Amith Anugu, Pankaj Singh, Dharambir Kashyap, Jillwin Joseph, Sheetal Naik, Subhabrata Sarkar, Kamran Zaman, Manpreet Dhaliwal, Shubham Nagar, Tanishq Gupta and Prasanna Honnavar
Microorganisms 2025, 13(7), 1557; https://doi.org/10.3390/microorganisms13071557 - 2 Jul 2025
Viewed by 493
Abstract
The global burden of respiratory viral infections is notable, which is attributed to their higher transmissibility compared to other viral diseases. Respiratory viruses are seen to have evolved resistance to available treatment options. Although vaccines and antiviral drugs control some respiratory viruses, this [...] Read more.
The global burden of respiratory viral infections is notable, which is attributed to their higher transmissibility compared to other viral diseases. Respiratory viruses are seen to have evolved resistance to available treatment options. Although vaccines and antiviral drugs control some respiratory viruses, this control is limited due to unexpected events, such as mutations and the development of antiviral resistance. The technology of proteolysis-targeting chimeras (PROTACs) has been emerging as a novel technology in viral therapeutics. These are small molecules that can selectively degrade target proteins via the ubiquitin–proteasome pathway. PROTACs as a therapy were initially developed against cancer, but they have recently shown promising results in their antiviral mechanisms by targeting viral and/or host proteins involved in the pathogenesis of viral infections. In this review, we elaborate on the antiviral potential of PROTACs as therapeutic agents and their potential as vaccine components against important respiratory viral pathogens, including influenza viruses, coronaviruses (SARS-CoV-2), and respiratory syncytial virus. Advanced applications of PROTAC antiviral strategies, such as hemagglutinin and neuraminidase degraders for influenza and spike proteins of SARS-CoV-2, are detailed in this review. Additionally, the role of PROTACs in targeting cellular mechanisms within the host, thereby preventing viral pathogenesis and eliciting an antiviral effect, is discussed. The potential of PROTACs as vaccines, utilizing proteasome-based virus attenuation to achieve a robust protective immune response, while ensuring safety and enhancing efficient production, is also presented. With the promises exhibited by PROTACs, this technology faces significant challenges, including the emergence of novel viral strains, tissue-specific expression of E3 ligases, and pharmacokinetic constraints. With advanced computational design in molecular platforms, PROTAC-based antiviral development offers an alternative, transformative path in tackling respiratory viruses. Full article
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17 pages, 1853 KiB  
Systematic Review
Safety, Immunogenicity, and Efficacy of COVID-19 Vaccines in Radiation–Oncology Patients: A Systematic Review and Meta-Analysis
by Paul Thöne, Margot Egger, Michael Stephan Gruber, Georg Gruber, Christina Kasassov, Dalma Nyiri, Eva Weis, Helene Werl, Leonhard Trinkl, Wolfgang Lilleby, Martin Clodi, Elisabeth Bräutigam, Benjamin Dieplinger, Annette Aigner and Hans Geinitz
Vaccines 2025, 13(7), 715; https://doi.org/10.3390/vaccines13070715 - 30 Jun 2025
Viewed by 435
Abstract
Background/Objectives: The COVID-19 pandemic significantly threatened cancer patients and oncologic care. The rollout of vaccines emerged as a critical milestone, despite the initial lack of evidence regarding their safety and efficacy in this population. This systematic review and meta-analysis evaluate the current [...] Read more.
Background/Objectives: The COVID-19 pandemic significantly threatened cancer patients and oncologic care. The rollout of vaccines emerged as a critical milestone, despite the initial lack of evidence regarding their safety and efficacy in this population. This systematic review and meta-analysis evaluate the current evidence on COVID-19 vaccination in patients undergoing radiotherapy (RT). Methods: PubMed, Livivo, Scopus, and Cochrane Library were systematically reviewed for relevant publications on COVID-19 vaccination in the context of radiation oncology, published by 19 April 2024. The treatment effects were calculated as the proportion of seroconverted individuals. Results: A total of 22 studies published between 2021 and 2024 were included, covering various aspects of vaccination, including safety, tolerability, qualitative and quantitative humoral responses, cellular responses, vaccination efficacy, and booster vaccinations. Notably, patients undergoing RT exhibited a high willingness to receive vaccination. Vaccination was overall well tolerated and safe, with a low incidence of side effects, which were primarily mild. The primary meta-analysis showed a seroconversion proportion of 91% [95% CI: 84–96%] overall, with a somewhat higher proportion of 93% in patients receiving RT alone, compared to 90% in patients receiving either RT or RT combined with chemotherapy. Furthermore, immunization during RT led to a sustained increase in antibody titers, with a notable long-term persistence of IgG. Conclusions: COVID-19 vaccines demonstrate excellent safety, immunogenicity, and efficacy in patients receiving RT, who also exhibit a high willingness to be vaccinated. The outcomes observed are comparable to those in healthy controls and superior to those seen in patients receiving other cancer treatments, such as chemotherapy. The vaccination of radiation oncology patients in future pandemics or epidemics is strongly advocated even during active treatment. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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17 pages, 623 KiB  
Review
A Review of Emerging Immunotherapeutic Strategies for IDH-Mutant Glioma
by Masih Tazhibi, Eric P. Grewal, Rishab Ramapriyan, Leland G. K. Richardson, Gust Vandecandelaere, Adrian Kalaw, Parker Kotlarz, Samuel J. Steuart, Jing Sun, Matthew Gaffey, Daniel P. Cahill, Julie J. Miller, William T. Curry and Bryan D. Choi
Cancers 2025, 17(13), 2178; https://doi.org/10.3390/cancers17132178 - 27 Jun 2025
Viewed by 690
Abstract
IDH-mutant gliomas (IMGs) are a unique subset of diffuse gliomas that follow a relatively indolent course compared to IDH-wildtype glioblastoma (GBM) but inevitably progress, often to a higher histologic grade. Current standard therapies, including surgery, chemoradiation, and the recently approved mutant IDH inhibitor [...] Read more.
IDH-mutant gliomas (IMGs) are a unique subset of diffuse gliomas that follow a relatively indolent course compared to IDH-wildtype glioblastoma (GBM) but inevitably progress, often to a higher histologic grade. Current standard therapies, including surgery, chemoradiation, and the recently approved mutant IDH inhibitor (mIDHi) vorasidenib, provide limited disease control and are not curative. Given the immunosuppressive tumor microenvironment (TME) driven by the mutant IDH enzyme and its associated oncometabolite 2-hydroxyglutarate (2-HG), novel immunotherapies offer a promising avenue for treatment. The goal of this paper is to review the main immunologic characteristics that distinguish IMG from GBM, including reduced T cell infiltration and function, fewer myeloid cells, and increased immune-dampening signaling. We also evaluate the preclinical and clinical evidence for immunotherapeutic approaches with the most potential to induce meaningful clinical activity, such as immune checkpoint inhibitors, CAR T cells, tumor vaccines, myeloid redirection, and oncolytic viruses. Despite significant advances in immunotherapy for IMG, fundamental questions persist, including optimal timing and combination strategies, mechanisms underpinning treatment resistance, and strategies to overcome the suppressive microenvironment. Future exploration of these treatment modalities, with a focus on mitigating soluble immunosuppressive factors in the TME, enhancing in situ T cell persistence, and leveraging novel antigen targets, is critical for advancing the state of therapy for this presently incurable group of tumors. Full article
(This article belongs to the Special Issue Emerging Research on Primary Brain Tumors)
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26 pages, 4776 KiB  
Article
Beneficial Cecal Microbiome Modulation in Turkeys Exposed to Probiotics and Vaccine After Multidrug-Resistant Salmonella Heidelberg Challenge
by Dhananjai Muringattu Prabhakaran, Anup Kollanoor Johny, Divek V. T. Nair, Shijinaraj Manjankattil, Timothy J. Johnson, Sally Noll and Kent M. Reed
Microbiol. Res. 2025, 16(7), 136; https://doi.org/10.3390/microbiolres16070136 - 25 Jun 2025
Viewed by 567
Abstract
Salmonella Heidelberg (SH) is a major serotype of foodborne Salmonella associated with turkeys. Understanding the effect of antibiotic alternatives (AAs) on the cecal microbiome of turkeys challenged with Salmonella could inform the development of microbiome-based strategies on farms. This study examined the effects [...] Read more.
Salmonella Heidelberg (SH) is a major serotype of foodborne Salmonella associated with turkeys. Understanding the effect of antibiotic alternatives (AAs) on the cecal microbiome of turkeys challenged with Salmonella could inform the development of microbiome-based strategies on farms. This study examined the effects of multiple AAs, such as probiotics, Lactobacillus and Propionibacterium, and a Salmonella Typhimurium vaccine, on the turkey cecal microbiome exposed to multidrug-resistant (MDR) SH. Microbial DNA was extracted from the cecal contents of 12-week-old commercial turkeys grown in five treatments for shotgun metagenomic sequencing and analysis: NC—Negative Control; PC—Salmonella Control; LAB—Lactobacillus treatment; PF—P. freudenreichii treatment; and VAC—vaccine treatment. Except for the NC, turkeys were challenged with MDR SH (108 CFU/turkey) on the 11th week. Differential abundance tests at the species level found that all AA treatments resulted in an increased abundance of multiple lactic acid-producing bacteria in the cecum compared to PC. In addition, multiple metabolic pathways were differentially abundant in AA treatments compared to PC. This study highlights the importance of AA strategies producing an increased abundance of lactic acid bacteria and critical metabolic pathways, indicating the potential of AAs to improve the gut health of turkeys during the Salmonella challenge. Full article
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28 pages, 6169 KiB  
Article
FairChain: A Trusted and Transparent Blockchain-Based Ecosystem for Drug Development for Nagoya Protocol Implementation
by Shada AlSalamah, Shaima A. Alnehmi, Anfal A. Abanumai, Asmaa H. Alnashri, Sara S. Alduhim, Norah A. Alnamlah, Khulood AlGhamdi, Haytham A. Sheerah, Sara A. Alsalamah and Hessah A. Alsalamah
Electronics 2025, 14(13), 2527; https://doi.org/10.3390/electronics14132527 - 22 Jun 2025
Viewed by 965
Abstract
The coronavirus pandemic has spread globally, affecting over 700 million people and resulting in over 7 million deaths. In response, global pharmaceutical companies and disease control centers have urgently sought effective treatments and vaccines. However, the rise of counterfeit drugs has become a [...] Read more.
The coronavirus pandemic has spread globally, affecting over 700 million people and resulting in over 7 million deaths. In response, global pharmaceutical companies and disease control centers have urgently sought effective treatments and vaccines. However, the rise of counterfeit drugs has become a significant concern amid this urgency. To standardize the legal provision and usage of genetic resources, the United Nations Development Program (UNDP) introduced the Nagoya Protocol. Despite advancements in drug research, the production process remains tedious, complex and vulnerable to fraud. FairChain addresses this pressing challenge by creating a transparent ecosystem that builds trust among all stakeholders throughout the Drug Development Life Cycle (DDLC) by using decentralized, immutable, and transparent blockchain technology. This makes FairChain the first digital health tool to implement the principles of the UNDP’s Nagoya Protocol among all stakeholders throughout all DDLC stages, starting with sample collection, to discovery and development, to preclinical research, to clinical development, to regulator review, and ending with post-market monitoring. Therefore, FairChain allows pharmaceutical companies to document the entire drug production process, landowners to monitor bio-samples from their land, doctors to share clinical research, and regulatory agencies such as the Food and Drug Authority to oversee samples and authorize production. FairChain should enhance transparency, foster trust and efficiency, and ensure a fair and traceable DDLC. To date, no blockchain-based framework has addressed the integration of traceability, auditability, and Nagoya Protocol compliance within a unified system architecture. This paper introduces FairChain, a system that formalizes these requirements in a modular, policy-aligned, and verifiable digital trust infrastructure. Full article
(This article belongs to the Section Computer Science & Engineering)
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12 pages, 649 KiB  
Review
Melanoma Vaccines: Comparing Novel Adjuvant Treatments in High-Risk Patients
by Joseph C. Broderick, Alexandra M. Adams, Elizabeth L. Barbera, Spencer Van Decar, Guy T. Clifton and George E. Peoples
Vaccines 2025, 13(6), 656; https://doi.org/10.3390/vaccines13060656 - 19 Jun 2025
Viewed by 680
Abstract
Background: The emergence of checkpoint inhibitors (CPIs) has significantly improved survival outcomes in later-stage melanoma. However, the efficacy of these treatments remains limited, with around 50% of later-stage melanoma patients experiencing recurrence. As variable response rates to CPIs persist, the development of cancer [...] Read more.
Background: The emergence of checkpoint inhibitors (CPIs) has significantly improved survival outcomes in later-stage melanoma. However, the efficacy of these treatments remains limited, with around 50% of later-stage melanoma patients experiencing recurrence. As variable response rates to CPIs persist, the development of cancer vaccines has emerged as a potential strategy to augment antitumor immune responses. Results: This review compares two promising personalized therapeutic cancer vaccine trials in advanced melanoma: Elios Therapeutics’ Tumor Lysate (TL) vaccine and Moderna’s mRNA-4157 vaccine. The TL vaccine, which utilizes yeast cell wall particles (YCWPs) loaded with autologous tumor lysate, and the mRNA-4157 vaccine, which encodes up to 34 patient-specific neoantigens, both aim to stimulate robust tumor-specific immune responses. Both trials were phase 2b randomized studies, with Elios Therapeutics’ trial employing a double-blind, placebo-controlled design, while Moderna’s was open-label. Both trials had roughly equivalent sample sizes (n = 187 and n = 157, respectively) with similar demographics and disease characteristics. The TL trial reported improvements in disease-free survival (DFS) with a hazard ratio (HR) of 0.52 (p < 0.01) over 36 months, whereas the mRNA-4157 trial demonstrated improvements in recurrence-free survival (RFS) with an HR of 0.56 (p = 0.053) over 18 months. The TL vaccine exhibited lower rates of related grade 3 adverse events (<1%) compared to the mRNA vaccine (12%). Key differences between the two trials include the use of CPIs, with 100% of patients in the mRNA trial receiving pembrolizumab versus 37% of the patients in the TL trial receiving either an anti-PD-1 or anti-CTLA-4. The production processes also varied significantly, with the mRNA vaccine requiring individualized sequencing and a 9-week production time, while the TL vaccine utilized tumor lysate with a 1–3-day production time. Conclusions: While both vaccines demonstrated promising efficacy, future phase 3 trials are needed to further evaluate their potential as adjuvant therapies for melanoma. This review highlights the comparative strengths and limitations of these vaccine platforms, providing insight into the evolving landscape of adjuvant cancer vaccines. Full article
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Article
Optimal Regional Control of a Time-Fractional Spatiotemporal SIR Model with Vaccination and Treatment Strategies
by Marouane Karim, Issam Khaloufi, Soukaina Ben Rhila, Mahmoud A. Zaky, Maged Z. Youssef and Mostafa Rachik
Fractal Fract. 2025, 9(6), 382; https://doi.org/10.3390/fractalfract9060382 - 16 Jun 2025
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Abstract
In this study, we analyze a time-fractional spatiotemporal SIR model in a specific area Ω. Taking into account the available resources, vaccines are allocated to region ω1Ω and treatments to region ω2Ω, which [...] Read more.
In this study, we analyze a time-fractional spatiotemporal SIR model in a specific area Ω. Taking into account the available resources, vaccines are allocated to region ω1Ω and treatments to region ω2Ω, which may or may not coincide. Our objective is to minimize infections and costs by implementing an optimal regional control strategy. We establish the existence of optimal controls and related solutions, providing a characterization of optimal control in terms of state and adjoint functions. We employ the forward–backward sweep method to solve the associated optimality system numerically. The findings indicate that a combined strategy of vaccination and treatment is more effective in reducing disease transmission from adjacent regions. Full article
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