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15 pages, 2593 KB  
Case Report
Successful Experience of Managing Resistant Antibody-Mediated Cardiac Allograft Rejection with Extracorporeal Photopheresis
by Lubov Korneva, Yulia Sazonova, Maria Bortsova, Maria Simonenko, Georgii Baratashvili, Olga Kalinina, Ekaterina Zaikova, Darina Sambur, Alexey Golovkin and Petr Fedotov
Transplantology 2025, 6(4), 29; https://doi.org/10.3390/transplantology6040029 - 5 Oct 2025
Viewed by 146
Abstract
Background/Clinical Significance: Development of acute antibody-mediated rejection (AMR) of allograft is one of the leading causes of mortality in heart-transplant recipients; however, the standard therapy does not always resolve severe forms of rejection. Extracorporeal photopheresis (ECP) is a method of immunomodulatory therapy [...] Read more.
Background/Clinical Significance: Development of acute antibody-mediated rejection (AMR) of allograft is one of the leading causes of mortality in heart-transplant recipients; however, the standard therapy does not always resolve severe forms of rejection. Extracorporeal photopheresis (ECP) is a method of immunomodulatory therapy that involves separating a patient’s white blood cells and treating them with a photosensitizer and ultraviolet A irradiation. Case Presentation: An 18-year-old female patient was urgently hospitalized with complaints of shortness of breath. She had undergone heart-transplant surgery 9 months before due to congenital heart disease restrictive cardiomyopathy, complicated with end-stage chronic heart failure. During the admission she admitted that for 3 weeks she discontinued tacrolimus and mycophenolate mofetil. AMR3 and CAV were verified. Conclusions: The use of standard approaches in the treatment of acute AMR is not always able to suppress an expressed immune reaction against the cardiac allograft, which leads to disruption of its function and rejection in the early or long-term follow-up. The inclusion of ECP in the treatment regimen allowed us to stabilize the patient’s condition and achieve regression in the severity of the AMR. It is believed that an important role in this was played by the activity of the immune system, which we assessed by changing the profile of cytokines, chemokines, and other growth factors. Thus, ECP demonstrated its effectiveness in the treatment of AMR of the cardiac allograft, with a change in the severity of the cytokine storm, as well as with an increase in the contribution of cytokines associated with the Th17 response. Full article
(This article belongs to the Section Transplant Immunology and Immunosuppressive Drugs)
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13 pages, 1133 KB  
Article
Evaluation of Nanodiamond-in-Oil Emulsion with Snake Venom to Enhance Potent Antibody Induction in Mice and Rabbits
by Min-Han Lin, Long-Jyun Su, Hsin-Hung Lin, Liang-Yu Chen, Asmaul Husna and Wang-Chou Sung
Nanomaterials 2025, 15(19), 1518; https://doi.org/10.3390/nano15191518 - 4 Oct 2025
Viewed by 328
Abstract
Nanodiamonds (NDs) are an innovative material in biomedical applications based on their excellent biocompatibility, nanoscale dimensions, and high surface area. In this study, we evaluated the potential of ND-in-oil emulsion to induce potent antibody responses in animals immunized with cobra venom. NDs demonstrated [...] Read more.
Nanodiamonds (NDs) are an innovative material in biomedical applications based on their excellent biocompatibility, nanoscale dimensions, and high surface area. In this study, we evaluated the potential of ND-in-oil emulsion to induce potent antibody responses in animals immunized with cobra venom. NDs demonstrated the capacity to bind complex venom proteins as stable conjugates, well dispersed in aqueous solution. Immunization of mice with cobra venom incorporated with ND-in-oil emulsion adjuvant (ND/venom) elicited strong venom-specific antibody responses with titers comparable to those induced by venom formulation with conventional Freund’s adjuvants (FA/venom). IgG subclass analysis revealed that ND- and FA-based formulations induced a Th2-biased immune response in mice. Moreover, antibodies elicited by ND/venom or FA/venom immunization specifically recognized the epitopes of the lethal component of short-chain neurotoxin and conferred full protection against lethal cobra venom challenge (3LD50). Further, ND/venom hyperimmunization was capable of inducing high levels of neutralizing antibodies in larger animals, rabbits, highlighting the potential for antivenom manufacturing. Notably, there were no obvious lesions at the injection sites of animals that received ND/venom, in contrast to those that received FA/venom. These findings indicated NDs as an effective and safe additive in venom formulation for antivenom production. Full article
(This article belongs to the Section Biology and Medicines)
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33 pages, 1855 KB  
Review
Pertussis—A Re-Emerging Threat Despite Immunization: An Analysis of Vaccine Effectiveness and Antibiotic Resistance
by Anna Duda-Madej, Jakub Łabaz, Ewa Topola, Hanna Bazan and Szymon Viscardi
Int. J. Mol. Sci. 2025, 26(19), 9607; https://doi.org/10.3390/ijms26199607 - 1 Oct 2025
Viewed by 189
Abstract
Pertussis is an infectious disease that contributes to hundreds of thousands of deaths worldwide each year. Despite the prevalence of preventive vaccination programs, there has been an increasing number of new cases of the disease over the past few decades. This poses a [...] Read more.
Pertussis is an infectious disease that contributes to hundreds of thousands of deaths worldwide each year. Despite the prevalence of preventive vaccination programs, there has been an increasing number of new cases of the disease over the past few decades. This poses a particular problem for the pediatric population among whom the highest mortality from the disease is recorded. Several reasons for this phenomenon can be mentioned, but what is particularly important from the microbiological point of view is the correlation of the increased number of pertussis cases with the introduction of a new form of vaccine—the acellular vaccine in place of the whole-cell vaccine. In this review, we summarized the current state of knowledge on potential factors that may contribute to the decline in immunization efficacy against the pathogen. The post-vaccination response profile, symptomatic of vaccination with vaccination-acellular, is characterized by recruitment of Th2 and Th17 lymphocytes; it has been reported that in the long term, this results in insufficient activation of B cells and low titers of antibodies to key bacterial antigens (hemagglutinin, pertactin). Moreover, the immune response proceeds by bypassing the recruitment of tissue-resident memory T cells, resulting in a lack of protection against colonization of the nasal cavity by the bacterium despite vaccination. The decline in vaccination efficacy should also be attributed to the phenotypic variability of Bordetella. The popularization of the PtxP3 strain, characterized by its ability to incompletely activate immune mechanisms, poses a real threat to public health. The growing resistance of B. pertussis to standardly used antibiotics including macrolides also remains a problem. This makes it difficult to eradicate pathogens from the nasal cavity area and increases the pool of bacterial carriers in the population area. The increasing prevalence of the disease prompts reflection on more effective methods of prevention. Particularly promising in this field seem to be new vaccines, especially mucosally implemented, e.g., intranasal, or developed on the basis of B. pertussis antigens other than those used so far. Full article
(This article belongs to the Section Molecular Immunology)
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23 pages, 1018 KB  
Review
Gender and Allergy: Mechanisms, Clinical Phenotypes, and Therapeutic Response—A Position Paper from the Società Italiana di Allergologia, Asma ed Immunologia Clinica (SIAAIC)
by Maria Teresa Ventura, Antonio Francesco Maria Giuliano, Elisa Boni, Luisa Brussino, Rosalba Buquicchio, Mariaelisabetta Conte, Maria Teresa Costantino, Maria Angiola Crivellaro, Irene Maria Rita Giuliani, Francesca Losa, Stefania Nicola, Paola Parronchi, Silvia Peveri, Erminia Ridolo, Paola Triggianese and Vincenzo Patella
Int. J. Mol. Sci. 2025, 26(19), 9605; https://doi.org/10.3390/ijms26199605 - 1 Oct 2025
Viewed by 445
Abstract
Sex and gender play a critical role in allergic diseases, influencing immune response, clinical phenotypes, treatment strategies, outcomes, and health-related quality of life. Despite mounting evidence across multiple studies examining sex/gender differences in a multitude of allergic diseases, most address isolated conditions, not [...] Read more.
Sex and gender play a critical role in allergic diseases, influencing immune response, clinical phenotypes, treatment strategies, outcomes, and health-related quality of life. Despite mounting evidence across multiple studies examining sex/gender differences in a multitude of allergic diseases, most address isolated conditions, not taking into consideration the vast interplay of hormonal, genetic, immunological, and sociocultural factors and their unique consequences for clinicians and researchers. With this position paper, we aim to assess currently available evidence on the sex- and gender-specific characteristics of the most common allergic diseases, providing an overview of present knowledge and future areas of improvement for clinicians and researchers. This position paper was developed by the Società Italiana di Allergologia, Asma ed Immunologia Clinica (SIAAIC): a panel of experts who conducted a literature review focusing on sex and gender differences across major allergic diseases. A consensus-based approach was employed to assess the immunological, clinical, and therapeutic implications of available evidence, offering a recommendation for researchers and clinicians alike. Data highlights marked differences driven by sex and gender in disease prevalence, immune pathways, clinical phenotype and severity, as well as therapeutic outcomes. Female patients appear to show a higher prevalence of Th2-driven ailments, autoimmune overlap, and allergic drug reactions, whereas males are more likely to experience fatal anaphylaxis and severe mastocytosis. Sex hormones can modulate multiple immune pathways leading to mast cell activation, antibody production, and cytokine expression, thus contributing to divergent disease trajectories. In conclusion, sex and gender are a key determinant in allergic diseases, and their integration in future research is essential to develop a tailored approach to treatment. Efforts should prioritise the identification of sex- and gender-specific biomarkers, therapeutic strategies, and equitable access to healthcare services. A sex- and gender-aware approach could potentially improve outcomes, optimise treatment strategies, and address current gaps in allergy practice. Full article
(This article belongs to the Section Molecular Immunology)
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19 pages, 4165 KB  
Article
Cytokine Expression and Haptoglobin Levels in Bovine Fetuses Spontaneously Aborted by Intracellular Infectious Agents and by Probable Infectious Etiology
by Emiliano Sosa, Natalia Pla, Dadin Prando Moore, Juan Agustín García, Lucía María Campero, María Andrea Fiorentino, Evangelina Miqueo, Erika González Altamiranda, Fermín Lázaro, Karen Morán, María Guillermina Bilbao, Silvina Quintana, Maia Solange Marín and Germán José Cantón
Animals 2025, 15(19), 2878; https://doi.org/10.3390/ani15192878 - 1 Oct 2025
Viewed by 646
Abstract
Intracellular pathogens such as Neospora caninum, Brucella abortus, and Bovine Viral Diarrhea Virus (BVDV) are major contributors to bovine abortions, yet many cases remain without a definitive etiological diagnosis despite inflammatory evidence. This study aimed to characterize the immune response in [...] Read more.
Intracellular pathogens such as Neospora caninum, Brucella abortus, and Bovine Viral Diarrhea Virus (BVDV) are major contributors to bovine abortions, yet many cases remain without a definitive etiological diagnosis despite inflammatory evidence. This study aimed to characterize the immune response in bovine fetuses aborted due to these intracellular agents, comparing them with fetuses showing inflammatory lesions of probable infectious origin and with negative controls. We analyzed cytokine expression (IFN-γ, TNFα, IL-4, IL-8, IL-12) and haptoglobin levels in mid- and late-gestation fetuses. Mid-gestation fetuses infected with intracellular agents exhibited elevated IFN-γ and IL-8 expressions, suggesting a Th1-type immune response, while late-gestation fetuses showed decreased of these cytokines, indicating a shift toward a Th2-type response. Probable infectious abortions at late gestation also showed downregulation of IFN-γ. No significant differences were observed in TNF-α and IL-12 expressions. Additionally, haptoglobin levels were lower in mid-gestation infected fetuses compared to controls. These findings highlight gestational age-dependent immune modulation in response to intracellular infections and suggest that other unidentified pathogens may contribute to abortions with inflammatory lesions but no confirmed etiology. This study enhances our understanding of fetal immune responses in bovine abortions and may support improved diagnostic approaches for reproductive losses in cattle. Full article
(This article belongs to the Special Issue Reproductive Diseases in Ruminants)
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18 pages, 1390 KB  
Article
Standardized Artemisia annua Exhibits Dual Antileishmanial Activity and Immunomodulatory Potential In Vitro
by Estefania Morua, Laura Cuyas, Carlos J. Bethencourt-Estrella, Atteneri López-Arencibia, Maria Garrido Martínez, Ana Sañudo Otero, Jacob Lorenzo-Morales, José E. Piñero, Anabel Yetano Cunchillos, Raquel Virto Resano and Luis Matías-Hernández
Vet. Sci. 2025, 12(10), 950; https://doi.org/10.3390/vetsci12100950 - 1 Oct 2025
Viewed by 361
Abstract
Leishmaniasis is a parasitic disease caused by Leishmania spp., transmitted by sandflies, and endemic in 98 countries. Leishmania infantum, the main agent of visceral leishmaniasis in Europe, commonly infects both humans and animals, with dogs as the principal domestic reservoir. Clinical manifestations [...] Read more.
Leishmaniasis is a parasitic disease caused by Leishmania spp., transmitted by sandflies, and endemic in 98 countries. Leishmania infantum, the main agent of visceral leishmaniasis in Europe, commonly infects both humans and animals, with dogs as the principal domestic reservoir. Clinical manifestations in dogs depend on the host immune response. A robust Th1 response facilitates macrophage activation and parasite control, while persistently elevated TNF-α and IL-6 can lead to chronic inflammation and tissue damage. Current treatments reduce parasite load but rarely achieve complete cure and are often associated with relapses and resistance. Artemisia annua, source of artemisinin, could be a promising alternative to canine leishmaniasis. Despite its potential, no published studies have investigated its effect specifically against Leishmania infantum as well as its possible dual action: antiparasitic and immunomodulation. We conducted in vitro evaluations of a standardized Artemisia annua extract. Leishmanicidal activity was assessed against both promastigote and amastigote stages, and cytokine modulation was evaluated in RAW 264.7 macrophages. The extract showed strong leishmanicidal activity without cytotoxicity and significantly reduced TNF-α and IL-6 levels under inflammatory conditions, and in both cases, efficiency was correlated with artemisinin content. These results support Artemisia annua as a promising safer therapeutic adjuvant candidate for canine leishmaniasis, targeting both the parasite and the host inflammatory response. Full article
(This article belongs to the Section Veterinary Microbiology, Parasitology and Immunology)
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21 pages, 4556 KB  
Article
AGS-v PLUS, a Mosquito Salivary Peptide Vaccine, Modulates the Response to Aedes Mosquito Bites in Humans
by Liam Barningham, Ian M. Carr, Siân Jossi, Megan Cole, Aiyana Ponce, Mara Short, Claudio Meneses, Joshua R. Lacsina, Jesus G. Valenzuela, Fabiano Oliveira, Matthew B. Laurens, DeAnna J. Friedman-Klabanoff, Olga Pleguezuelos, Lucy F. Stead and Clive S. McKimmie
Vaccines 2025, 13(10), 1026; https://doi.org/10.3390/vaccines13101026 - 30 Sep 2025
Viewed by 562
Abstract
Background: The global health burden of mosquito-borne viruses, including dengue, yellow fever, Zika, and chikungunya, is rising due to climate change and globalisation, which favour mosquito habitat expansion. The genetic diversity of these viruses complicates the development of virus-specific vaccines or antivirals, highlighting [...] Read more.
Background: The global health burden of mosquito-borne viruses, including dengue, yellow fever, Zika, and chikungunya, is rising due to climate change and globalisation, which favour mosquito habitat expansion. The genetic diversity of these viruses complicates the development of virus-specific vaccines or antivirals, highlighting the need for pan-viral strategies. As the common vector for these pathogens, mosquitoes and specifically their salivary proteins represent a promising target for such interventions. Mosquito saliva, secreted into the skin during biting, has immunomodulatory effects that can enhance host susceptibility to infection, but these mechanisms are not well defined in humans. Methods: The objective of this study was to determine whether AGS-v PLUS, a vaccine targeting mosquito salivary antigens, could modulate the human skin immune response to mosquito biting and potentially promote antiviral bystander immunity. In a Phase I trial, healthy volunteers were vaccinated with AGS-v PLUS (with or without adjuvant) or placebo, and three weeks later, they were exposed to bites from Aedes albopictus and Aedes aegypti mosquitoes. Skin biopsies from bitten and unbitten sites were analysed by transcriptomic profiling. Results: In placebo recipients, mosquito biting elicited a marked adaptive immune response at 48 h, characterised by CD4+ Th1 and CD8+ T cell signatures and leukocyte recruitment. While responses to Ae. aegypti and Ae. albopictus bites were broadly similar, those to Ae. albopictus were stronger. Vaccination with AGS-v PLUS, particularly with adjuvant, enhanced Th1 and CD8+ T cell-associated gene expression while suppressing pathways linked to neutrophilic inflammation and epithelial stress, which together may provide enhanced antiviral capacity. Conclusions: These findings demonstrate that targeting the host response to mosquito saliva via vaccination can reprogram the skin’s immune response to mosquito bites, supporting a novel and broadly applicable pan-viral strategy to mitigate the impact of arboviral diseases. Full article
(This article belongs to the Section Vaccines against Tropical and other Infectious Diseases)
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13 pages, 1961 KB  
Article
A CpG 1018S/QS-21-Adjuvanted HBsAg Therapeutic Vaccine as a Novel Strategy Against HBV
by Zixuan Wang, Jing Wu, Xiaohan Meng, He Weng, Qiang Li, Lin Li, Zhenhao Ma, Sirong Bi, Qiuju Han, Huajun Zhao, Cunbao Liu and Deping Meng
Vaccines 2025, 13(10), 1014; https://doi.org/10.3390/vaccines13101014 - 29 Sep 2025
Viewed by 456
Abstract
Chronic hepatitis B virus (HBV) infection remains a major global health challenge, substantially contributing to liver-related morbidity and mortality. Background/Objectives: Developing therapeutic strategies that overcome immune tolerance and achieve functional cures is an urgent priority. Methods: In this study, we report [...] Read more.
Chronic hepatitis B virus (HBV) infection remains a major global health challenge, substantially contributing to liver-related morbidity and mortality. Background/Objectives: Developing therapeutic strategies that overcome immune tolerance and achieve functional cures is an urgent priority. Methods: In this study, we report a therapeutic vaccine comprising hepatitis B surface antigen (HBsAg) formulated with the dual adjuvant system CpG 1018S and QS-21. The immunogenicity and therapeutic efficacy of this vaccine were systematically evaluated in an rAAV8-HBV1.3-established chronic HBV mouse model. Results: The vaccine elicited a robust Th1-skewed immune response, characterized by elevated anti-HBs IgG2b titers and an increased IgG2b/IgG1 ratio. Notably, immunized mice showed markedly reduced circulating HBsAg levels. Mechanistically, the CpG 1018S and QS-21 adjuvant system enhanced dendritic cell activation, maturation, and antigen presentation, expanded HBV-specific CD4+ and CD8+ T cell populations, and attenuated the expression of the exhaustion markers TIM-3 and TIGIT. Additionally, immunized mice exhibited restored T cell polyfunctionality, with an increased secretion of effector cytokines, including TNF-α and IL-21. These responses collectively contributed to the reversal of T cell exhaustion and breakdown of immune tolerance, facilitating sustained viral suppression. Conclusions: Our findings demonstrate that the CpG 1018S/QS-21-adjuvanted vaccine induces potent humoral and cellular immunity against chronic HBV infection and represents a promising candidate for clinical chronic HBV (CHB) treatment. Full article
(This article belongs to the Section Hepatitis Virus Vaccines)
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19 pages, 2191 KB  
Article
Evaluation of Quillaja brasiliensis Saponin-Based Nanoparticles Combined with Leucine Aminopeptidases for Immunoprotection of Sheep Against Fasciola hepatica
by Jackeline Checa, Antonella Goyeche, Renzo Vettorazzi, Pablo Alonzo, Oscar Correa, Walter Norbis, Estela Castillo, Martin Cancela, Andrea Rossi, Fernando Silveira and Gabriela Maggioli
Vaccines 2025, 13(10), 1008; https://doi.org/10.3390/vaccines13101008 - 26 Sep 2025
Viewed by 364
Abstract
Background: Fasciola hepatica causes important economic losses in ruminants with only pharmacological treatments currently available, which produces several secondary problems. Because of this, vaccines have become an interesting alternative. Leucine aminopeptidases (LAPs) are attractive vaccine targets against fasciolosis since they play essential [...] Read more.
Background: Fasciola hepatica causes important economic losses in ruminants with only pharmacological treatments currently available, which produces several secondary problems. Because of this, vaccines have become an interesting alternative. Leucine aminopeptidases (LAPs) are attractive vaccine targets against fasciolosis since they play essential roles in the parasite such as host invasion and nutrient acquisition. To characterize immune responses, we produced two recombinant F. hepatica LAPs (FhLAP1 and FhLAP2), formulated with ISCOM-matrices (IMXs) nanoparticles from Quillaja brasiliensis saponins. Methods: Forty female Corriedale sheep were assigned to four groups (n = 10): FhLAP1/IMX, FhLAP1/FhLAP2/IMX, IMX (control), and FhLAP1/Adj50 (Adjuvac 50). Animals received two subcutaneous immunizations at weeks 0 and 4 and were challenged orally with 200 metacercariae at week 6. Results: FhLAP1 and FhLAP1/FhLAP2 induced specific IgG responses, with the predominance of the IgG1 response. However, these responses were lower than those generated by FhLAP1 formulated with Adj50. A qPCR analysis revealed that FhLAP1/IMX stimulated a Th1-type response profile before the challenge, but this profile was not sustained after infection. The post-infection profile of FhLAP1/FhLAP2/IMX was more congruent with expected values despite not achieving a robust IFN-γ expression. No significant differences in the fluke burden were observed. Conclusions: Further research on the optimal antigen/adjuvant combination in ruminants is encouraged. For instance, a higher concentration of adjuvant in the formulation used in this work may enhance the strength and duration of the inflammatory response and improve protective immunity against fasciolosis. Full article
(This article belongs to the Special Issue Parasitic Infections: Therapy for Host Immunity and Vaccination)
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19 pages, 317 KB  
Review
Overview of Commercial Vaccines Against Canine Visceral Leishmaniasis: Current Landscape and Future Directions
by Josiane Aparecida Martiniano de Pádua, Diego Ribeiro, Victor Freire Ferreira de Aguilar, Tuane Ferreira Melo, Lilian Lacerda Bueno, Ana Laura Grossi de Oliveira, Ricardo Toshio Fujiwara and Kelly Moura Keller
Pathogens 2025, 14(10), 970; https://doi.org/10.3390/pathogens14100970 - 25 Sep 2025
Viewed by 478
Abstract
Visceral leishmaniasis is a zoonosis commonly caused in Brazil by the parasite Leishmania infantum. This protozoan parasite can infect several species of mammals, with dogs being the main reservoir in urban areas. Several methods are used to prevent the disease, including collars [...] Read more.
Visceral leishmaniasis is a zoonosis commonly caused in Brazil by the parasite Leishmania infantum. This protozoan parasite can infect several species of mammals, with dogs being the main reservoir in urban areas. Several methods are used to prevent the disease, including collars impregnated with 4% deltamethrin to prevent contact between the sandfly and the animal, and vaccines. Vaccines aim to stimulate an immune response that can effectively fight the parasite, with the Th1 immune response being the most desired. There are several research groups around the world dedicated to testing new immunogens against Leishmania spp. and there are currently two commercially available vaccines used to prevent the disease, Neoleish® and Leti-Fend®. Leish-Tec®, a vaccine previously licensed for use in dogs in Brazil, was suspended in May 2023 due to non-compliance in some batches. This also happened with CaniLeish®, which was discontinued by the European Commission in October 2023. These vaccines have different characteristics that influence their use as a public health measure, and therefore the objective of this review is to describe these immunogens, their characteristics, and their use as a collective prevention measure for canine visceral leishmaniasis. Full article
(This article belongs to the Special Issue Leishmania & Leishmaniasis)
15 pages, 1602 KB  
Review
Understanding Insect Bite Hypersensitivity in Horses: A Narrative Review for Clinical Practice
by Alexandra Nicoleta Mureșan, Ilinca Maria Țăpuc and Daniela Mihaela Neagu
Allergies 2025, 5(3), 31; https://doi.org/10.3390/allergies5030031 - 22 Sep 2025
Viewed by 533
Abstract
Insect bite hypersensitivity (IBH) is a seasonally recurrent allergic dermatitis representing one of the most prevalent dermatological conditions in horses worldwide. This condition, driven by hypersensitivity to salivary allergens of Culicoides spp., causes substantial discomfort, welfare impairment, and potentially economic loss in equine [...] Read more.
Insect bite hypersensitivity (IBH) is a seasonally recurrent allergic dermatitis representing one of the most prevalent dermatological conditions in horses worldwide. This condition, driven by hypersensitivity to salivary allergens of Culicoides spp., causes substantial discomfort, welfare impairment, and potentially economic loss in equine populations. The pathogenesis of IBH is complex, involving genetic predisposition, epithelial barrier dysfunction, and a skewed T-helper 2 (Th2)-mediated immune response with elevated IgE production and eosinophilic inflammation. Advances in immunogenetics and molecular immunology have improved the understanding of the disease’s multifactorial nature. Research on immunotherapy and cytokine-targeted treatments is contributing to the development of more effective therapeutic options. This review synthesizes current knowledge on the immunopathogenesis and genetic determinants of IBH and discusses both conventional and emerging strategies for its clinical management. Full article
(This article belongs to the Section Veterinary Allergy)
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19 pages, 4885 KB  
Article
Induction of Sustained Immunity Following Vaccination with Live Attenuated Trypanosoma cruzi Parasites Combined with Saponin-Based Adjuvants
by Brenda A. Zabala, María Elisa Vázquez, Daniela E. Barraza, Andrea C. Mesías, Federico Ramos, Alejandro Uncos, Iván S. Marcipar, Leonardo Acuña and Cecilia Pérez Brandán
Biology 2025, 14(9), 1298; https://doi.org/10.3390/biology14091298 - 20 Sep 2025
Viewed by 427
Abstract
Chagas disease, caused by Trypanosoma cruzi, remains a major health concern in Latin America, particularly affecting low-income and rural communities. Among the many vaccine strategies explored, live attenuated parasites have shown the strongest ability to trigger protective immune responses. In this study, [...] Read more.
Chagas disease, caused by Trypanosoma cruzi, remains a major health concern in Latin America, particularly affecting low-income and rural communities. Among the many vaccine strategies explored, live attenuated parasites have shown the strongest ability to trigger protective immune responses. In this study, we investigated whether adding saponin-based adjuvants—Immunostimulant Particle Adjuvant (ISPA) and Quil-A—could improve the effectiveness and safety of a live parasite attenuated T. cruzi vaccine. Mice were vaccinated with a T. cruzi attenuated strain (TCC) alone or in combination with each adjuvant, and immunoglobulin G (IgG) subtypes in the serum of vaccinated mice, and interferon gamma (IFN-γ) and interleukin-10 (IL-10) in the supernatants of stimulated cells were measured at two weeks and twelve months post-vaccination. While protection levels were similar across all groups, the adjuvants assist in modulating the immune response over time: ISPA and Quil-A initially shifted antibody production toward IgG1 but later favored a balanced TH1/TH2 profile. ISPA also promoted long-term regulation through increased IL-10. Both adjuvants reduced tissue inflammation and enhanced clearance of vaccine-derived parasites. These findings suggest that while adjuvants may not boost protection directly, they significantly improve vaccine safety and immune quality, reinforcing their value in developing better vaccines for Chagas disease. Full article
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2 pages, 152 KB  
Retraction
RETRACTED: Haghmorad et al. Oral Administration of Myelin Oligodendrocyte Glycoprotein Attenuates Experimental Autoimmune Encephalomyelitis through Induction of Th2/Treg Cells and Suppression of Th1/Th17 Immune Responses. Curr. Issues Mol. Biol. 2022, 44, 5728–5740
by Dariush Haghmorad, Bahman Yousefi, Majid Eslami, Ali Rashidy-Pour, Mahdieh Tarahomi, Maryam Jadid Tavaf, Azita Soltanmohammadi, Simin Zargarani, Aleksandr Kamyshnyi and Valentyn Oksenych
Curr. Issues Mol. Biol. 2025, 47(9), 781; https://doi.org/10.3390/cimb47090781 - 20 Sep 2025
Viewed by 301
Abstract
The journal retracts the article “Oral Administration of Myelin Oligodendrocyte Glycoprotein Attenuates Experimental Autoimmune Encephalomyelitis through Induction of Th2/Treg Cells and Suppression of Th1/Th17 Immune Responses” [...] Full article
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
11 pages, 837 KB  
Article
Th2 Suppression Through Antigen Liver Expression Using mRNA-LNP Technology
by Kazunori Arai, Hanae Toyonaga, Lei Cheng and Hirotsugu Tanaka
Biomedicines 2025, 13(9), 2297; https://doi.org/10.3390/biomedicines13092297 - 19 Sep 2025
Viewed by 441
Abstract
Background: Messenger RNA-lipid nanoparticle (mRNA-LNP) is a cutting-edge nucleic acid intracellular delivery technology. Although the clinical use of the mRNA vaccine is being actively developed, the use of mRNA-LNP technology in common diseases such as allergies is still being investigated. The purpose of [...] Read more.
Background: Messenger RNA-lipid nanoparticle (mRNA-LNP) is a cutting-edge nucleic acid intracellular delivery technology. Although the clinical use of the mRNA vaccine is being actively developed, the use of mRNA-LNP technology in common diseases such as allergies is still being investigated. The purpose of this study is to test if immune response can be suppressed when an antigen is expressed in mice liver tissue with mRNA-LNP technology. Methods: We first designed mRNA which the ovalbumin (OVA) antigen expresses on the surface of the cells, and synthesized mRNA were encapsulated into LNP. This OVA-mRNA-LNP was evaluated with an OVA-sensitized mouse model. Splenocytes from OVA-sensitized mice were cultured with ex vivo OVA stimulation for Th2 cytokine production and Treg population analysis. Furthermore, OVA-mRNA-LNP was evaluated by both prophylactic and therapeutic administration in an OVA-induced mice airway inflammation model. Results: Th2 cytokines such as IL-4 and IL-5 were suppressed and the Treg population was increased in ex vivo OVA-stimulated splenocytes isolated from the OVA-mRNA-LNP administered group. Moreover, suppression of Th2 cytokines in Bronchoalveolar Lavage Fluid (BALF) from both the prophylactic and therapeutic OVA-mRNA-LNP administered cohort was observed (40–80% reduction in Th2 cytokines). Conclusions: The data suggests that mRNA-LNP technology, which is a safe, non-viral gene delivery system, can be an effective approach to suppress allergen-induced inflammation by expressing antigen in the liver tissue. Full article
(This article belongs to the Special Issue Advances in Novel Drug Discovery, Synthesis, and Evaluation)
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25 pages, 1836 KB  
Review
The STAT Signaling Pathway in HIV-1 Infection: Roles and Dysregulation
by Manlio Tolomeo and Antonio Cascio
Int. J. Mol. Sci. 2025, 26(18), 9123; https://doi.org/10.3390/ijms26189123 - 18 Sep 2025
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Abstract
The STAT (Signal Transducer and Activator of Transcription) signaling pathway plays a central role in immune regulation by mediating cytokine responses and orchestrating both innate and adaptive immunity. Although CD4+ T cell depletion is the main driver of HIV-1–induced immunodeficiency, the virus also [...] Read more.
The STAT (Signal Transducer and Activator of Transcription) signaling pathway plays a central role in immune regulation by mediating cytokine responses and orchestrating both innate and adaptive immunity. Although CD4+ T cell depletion is the main driver of HIV-1–induced immunodeficiency, the virus also exerts a significant and often underestimated impact by disrupting the function of STAT family members, thereby exacerbating immune imbalance and accelerating disease progression. Specifically, HIV-1 suppresses STAT1 activation, impairing the induction of antiviral genes; inhibits IL-23–driven STAT3 activation in CD4+ Th17 cells with a reduction in IL-17; alters STAT3-dependent functions in antigen-presenting cells; and imposes profound—and at times opposing—dysregulations of STAT5, including the induction of a truncated isoform that contributes to latency. Notably, pharmacological inhibition of the JAK/STAT axis, particularly with JAK2 inhibitors, has been shown to reduce integrated proviral DNA and viral replication in vitro and in early clinical studies. This review provides an updated overview of the roles of individual STAT proteins in HIV-1 infection and pathogenesis, emphasizing the intricate interplay between viral factors and host signaling, highlighting the potential therapeutic implications, and suggesting that immunological assessment in HIV-1 patients should extend beyond CD4+ T cell counts and the CD4/CD8 ratio to include functional analysis of STAT signaling for deeper insights into immune dysfunction and chronic inflammation. Full article
(This article belongs to the Special Issue Molecular Mechanisms of HIV Infection, Pathogenesis and Persistence)
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