Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment in humans; however, research on ICIs in cats remains limited, and no clinical trials have been conducted for feline neoplastic diseases. Here, we developed a mouse monoclonal antibody (clone 1A1–2) targeting the feline PD-1 molecule and generated a mouse-feline chimeric antibody (1A1–2-fIgG1) by replacing the constant region of 1A1–2 with that of feline IgG1. However, administering 1A1–2-fIgG1 to cats may deplete PD-1-expressing effector T-cells via complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis, as feline IgG1 binds to CD64, CD16, and C1q. We engineered two 1A1–2-fIgG1 mutants with amino acid substitutions in the constant region to reduce the interactions between the Fc fragment and C1q or FcγRs and mitigate these effector functions. These mutations successfully abolished the binding to CD64, CD32, and CD16 while preserving the affinity for FcRn, which is essential in maintaining the half-life of antibodies in the blood. Furthermore, the mutants exhibited impaired binding to C1q. Despite these modifications, the mutated antibodies effectively restored IFN-γ production, which had been suppressed by PD-1/PD-L1 signaling in stimulated lymphocytes, to levels comparable to those of the original antibody. These findings reveal that the engineered antibodies have potential for future clinical applications in feline oncology.
{"title":"Engineering an Fc-inert feline IgG1 by targeted mutations: Application to anti-PD-1 antibody development","authors":"Shoma Nishibori , Yoshiho Takeda , Masaya Igase , Takuya Mizuno","doi":"10.1016/j.vetimm.2025.111000","DOIUrl":"10.1016/j.vetimm.2025.111000","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment in humans; however, research on ICIs in cats remains limited, and no clinical trials have been conducted for feline neoplastic diseases. Here, we developed a mouse monoclonal antibody (clone 1A1–2) targeting the feline PD-1 molecule and generated a mouse-feline chimeric antibody (1A1–2-fIgG<sub>1</sub>) by replacing the constant region of 1A1–2 with that of feline IgG<sub>1</sub>. However, administering 1A1–2-fIgG<sub>1</sub> to cats may deplete PD-1-expressing effector T-cells via complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis, as feline IgG<sub>1</sub> binds to CD64, CD16, and C1q. We engineered two 1A1–2-fIgG<sub>1</sub> mutants with amino acid substitutions in the constant region to reduce the interactions between the Fc fragment and C1q or FcγRs and mitigate these effector functions. These mutations successfully abolished the binding to CD64, CD32, and CD16 while preserving the affinity for FcRn, which is essential in maintaining the half-life of antibodies in the blood. Furthermore, the mutants exhibited impaired binding to C1q. Despite these modifications, the mutated antibodies effectively restored IFN-γ production, which had been suppressed by PD-1/PD-L1 signaling in stimulated lymphocytes, to levels comparable to those of the original antibody. These findings reveal that the engineered antibodies have potential for future clinical applications in feline oncology.</div></div>","PeriodicalId":23511,"journal":{"name":"Veterinary immunology and immunopathology","volume":"288 ","pages":"Article 111000"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-09-15DOI: 10.1016/j.vetimm.2025.111004
Pernille A. Madsen , Kevin J. Bogotá , Darya Vodolazska , Mette S. Hedemann , Andrew R. Williams , Charlotte Lauridsen
Enterotoxigenic E. coli infection is a major cause of post-weaning diarrhea in pigs and is associated with systemic inflammation and oxidative stress. This study aimed to characterize temporal changes in biomarkers of inflammation and oxidative stress in response to an E. coli lipopolysaccharide (LPS) challenge, providing insights into host immune responses. Ten female pigs (27.9 kg BW; ∼3 months old) were infused with LPS derived from E. coli O111:B4 at LOW (0.75 µg LPS/kg BW) or MODERATE (1.50 µg LPS/kg BW) dosages. Thirteen blood samples were collected via venous catheter at 0 (pre-infusion), and from 0.5 to 72 h post LPS infusion. Rectal temperature, blood cytokines, acute-phase proteins, and oxidative stress markers were measured. A semi-targeted metabolomics approach was applied to investigate oxidative stress markers, including 8-iso-prostaglandin F₂α (8-iso-PGF₂α). Rectal temperature peaked at 3 h and returned to pre-infusion levels by 8 h. Plasma C-reactive protein (CRP) peaked at 12 h, while haptoglobin peaked at 24 h after LPS infusion. Pig major acute-phase protein (Pig-MAP) peaked at 24 h (LOW) and 36 h (MODERATE). Malondialdehyde (MDA) peaked between 0.5 and 1 h and returned to pre-infusion levels within 12 h. The cytokines IL-6, IFN-γ, IL-10 and IL-1β peaked between 1 and 3 h post-infusion. Moreover, cortisol increased rapidly, peaking at 2 h post LPS infusion. These findings indicate distinct temporal responses of inflammatory and oxidative stress markers following LPS challenge, supporting their use as potential biomarkers for evaluating interventions modulating infection-induced oxidative stress in pigs.
{"title":"Temporal changes in biomarkers of oxidative stress and inflammation in pigs after intravenous administration of E. coli lipopolysaccharide","authors":"Pernille A. Madsen , Kevin J. Bogotá , Darya Vodolazska , Mette S. Hedemann , Andrew R. Williams , Charlotte Lauridsen","doi":"10.1016/j.vetimm.2025.111004","DOIUrl":"10.1016/j.vetimm.2025.111004","url":null,"abstract":"<div><div>Enterotoxigenic <em>E. coli</em> infection is a major cause of post-weaning diarrhea in pigs and is associated with systemic inflammation and oxidative stress. This study aimed to characterize temporal changes in biomarkers of inflammation and oxidative stress in response to an <em>E. coli</em> lipopolysaccharide (LPS) challenge, providing insights into host immune responses. Ten female pigs (27.9 kg BW; ∼3 months old) were infused with LPS derived from <em>E. coli</em> O111:B4 at LOW (0.75 µg LPS/kg BW) or MODERATE (1.50 µg LPS/kg BW) dosages. Thirteen blood samples were collected via venous catheter at 0 (pre-infusion), and from 0.5 to 72 h post LPS infusion. Rectal temperature, blood cytokines, acute-phase proteins, and oxidative stress markers were measured. A semi-targeted metabolomics approach was applied to investigate oxidative stress markers, including 8-iso-prostaglandin F₂α (8-iso-PGF₂α). Rectal temperature peaked at 3 h and returned to pre-infusion levels by 8 h. Plasma C-reactive protein (CRP) peaked at 12 h, while haptoglobin peaked at 24 h after LPS infusion. Pig major acute-phase protein (Pig-MAP) peaked at 24 h (LOW) and 36 h (MODERATE). Malondialdehyde (MDA) peaked between 0.5 and 1 h and returned to pre-infusion levels within 12 h. The cytokines IL-6, IFN-γ, IL-10 and IL-1β peaked between 1 and 3 h post-infusion. Moreover, cortisol increased rapidly, peaking at 2 h post LPS infusion. These findings indicate distinct temporal responses of inflammatory and oxidative stress markers following LPS challenge, supporting their use as potential biomarkers for evaluating interventions modulating infection-induced oxidative stress in pigs.</div></div>","PeriodicalId":23511,"journal":{"name":"Veterinary immunology and immunopathology","volume":"288 ","pages":"Article 111004"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-09-05DOI: 10.1016/j.vetimm.2025.110997
María Celeste Moran , Agostina Tammone Santos , Paula Dominguez , Lucila Moriones , María Victoria Nieto Farias , Laura Maté , Juan Agustín García , Tobias Kuhn , Fernando Alberto Paolicchi , María Andrea Fiorentino , Marcelo Gastón Rodriguez , Jorge Pablo García , Claudio Santiago Cacciato , Fernando Alberto Goldbaum , Vanesa Zylberman , Romina Paola Pardo , Sabrina Foscaldi , Claudia María Lützelschwab , Giuliana Lupi , Iván Santiago Marcipar , Silvia Marcela Estein
Brucella ovis (B. ovis) is the etiological agent of ram-contagious epididymitis, the leading cause of reproductive disorders in flocks worldwide. Although the attenuated B. melitensis Rev.1 strain gives heterologous protection against this pathogen, it has important disadvantages. Subunit vaccines could provide a safer alternative that considers the One Health approach. Polymeric BLSOmp31 was previously identified as a protective immunogen against this pathogen. In our previous work in BALB/c mice, we evaluated the performance of BLSOmp31 formulated in a new cage-like particle adjuvant called ISPA. In the present study, we administered BLSOmp31, which was formulated in a new low-cost variant of ISPA called ISPA YOLK (BLSOmp31/ISPA YOLK). This formulation was given to rams through both subcutaneous and ocular routes. We evaluated the systemic and mucosal immune responses and assessed its protective capacity against B. ovis. BLSOmp31/ISPA YOLK administered by both routes induced systemic and variable mucosal IgG and IgA antibody response, without interference in the serological diagnosis. Additionally, this formulation induced significant specific cellular immune responses and an increase in the relative expression levels of cytokine genes in peripheral blood mononuclear cells with a mixed Th1/Th2 profile. While this vaccine did not prevent experimental infection with B. ovis, parenterally immunized rams had fewer infected organs and less severe histopathological changes in reproductive organs compared to animals vaccinated by ocular route and non-immunized rams. In contrast, this formulation, whether administered by SC or CONJ route could reduce the elimination of B. ovis through semen, and minimize the risk of spreading the infection.
{"title":"Evaluation of the efficacy of polymeric antigen BLSOmp31 formulated in a new cage-like particle adjuvant (ISPA YOLK) administered by parenteral or mucosal routes against Brucella ovis in rams","authors":"María Celeste Moran , Agostina Tammone Santos , Paula Dominguez , Lucila Moriones , María Victoria Nieto Farias , Laura Maté , Juan Agustín García , Tobias Kuhn , Fernando Alberto Paolicchi , María Andrea Fiorentino , Marcelo Gastón Rodriguez , Jorge Pablo García , Claudio Santiago Cacciato , Fernando Alberto Goldbaum , Vanesa Zylberman , Romina Paola Pardo , Sabrina Foscaldi , Claudia María Lützelschwab , Giuliana Lupi , Iván Santiago Marcipar , Silvia Marcela Estein","doi":"10.1016/j.vetimm.2025.110997","DOIUrl":"10.1016/j.vetimm.2025.110997","url":null,"abstract":"<div><div><em>Brucella ovis</em> (<em>B. ovis</em>) is the etiological agent of ram-contagious epididymitis, the leading cause of reproductive disorders in flocks worldwide. Although the attenuated <em>B. melitensis</em> Rev.1 strain gives heterologous protection against this pathogen, it has important disadvantages. Subunit vaccines could provide a safer alternative that considers the One Health approach. Polymeric BLSOmp31 was previously identified as a protective immunogen against this pathogen. In our previous work in BALB/c mice, we evaluated the performance of BLSOmp31 formulated in a new cage-like particle adjuvant called ISPA. In the present study, we administered BLSOmp31, which was formulated in a new low-cost variant of ISPA called ISPA YOLK (BLSOmp31/ISPA YOLK). This formulation was given to rams through both subcutaneous and ocular routes. We evaluated the systemic and mucosal immune responses and assessed its protective capacity against <em>B. ovis</em>. BLSOmp31/ISPA YOLK administered by both routes induced systemic and variable mucosal IgG and IgA antibody response, without interference in the serological diagnosis. Additionally, this formulation induced significant specific cellular immune responses and an increase in the relative expression levels of cytokine genes in peripheral blood mononuclear cells with a mixed Th1/Th2 profile. While this vaccine did not prevent experimental infection with <em>B. ovis</em>, parenterally immunized rams had fewer infected organs and less severe histopathological changes in reproductive organs compared to animals vaccinated by ocular route and non-immunized rams. In contrast, this formulation, whether administered by SC or CONJ route could reduce the elimination of <em>B. ovis</em> through semen, and minimize the risk of spreading the infection.</div></div>","PeriodicalId":23511,"journal":{"name":"Veterinary immunology and immunopathology","volume":"288 ","pages":"Article 110997"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-09-16DOI: 10.1016/j.vetimm.2025.111003
Ahmed A. Azab , Mahmoud Samir , Salah Zakaria , Hassna Maged , Nahed Yehia , Mohamed Taha , Ahmed A. El-Sanousi , Ahmed Aly Khalil
Background
Newcastle disease virus (NDV) and infectious bronchitis virus (IBV) cause annual global economic losses exceeding $1 billion in the poultry industry. In Egypt remain major threats to poultry production. emerging variant strains increasingly challenge current vaccination strategies, necessitating more effective control measures.
Methods
We evaluated a novel bivalent inactivated vaccine (Valley Vac IB3 NDVg7) containing recent field isolates (NDV genotype VII and IBV variant-II) against a commercial bivalent vaccine. Seventy-one-day-old commercial chicks were randomized into seven groups (n = 10). Groups 1,4 and 2,5 received the novel and commercial vaccines respectively, while groups 3,6 served as unvaccinated controls, and group 7 as a negative control. At three weeks post-vaccination, groups were challenged with either NDV-B7-RLQP-CH-EG-12 or IBV-Eg/15170F-SP1/2015. Protection rates, viral shedding, ciliostasis, and immune responses were evaluated using standardized protocols.
Results
The novel vaccine demonstrated significantly superior protection (90–100 %, P < 0.01) compared to the commercial vaccine (60–70 %) against both viruses. Viral shedding in the novel vaccine group was reduced by 2.1 log10 (P < 0.001) by day 5 post-challenge, achieving complete clearance by day 7. Ciliostasis protection scores were significantly higher in the novel vaccine group (87.33–100) versus the commercial vaccine (35–78.33, P < 0.001). Serological responses showed stronger and more sustained antibody titers in the novel vaccine group for both NDV (8.0 ± 2.0 vs 6.7 ± 1.0 log₂, P < 0.01) and IBV (4612.6 ± 839.35 vs 3340.5 ± 1650.16 ELISA units, P < 0.01) through three weeks post-vaccination.
Conclusions
The novel bivalent vaccine incorporating contemporary field strains provided significantly enhanced protection against current NDV and IBV variants, offering a promising strategy for improved disease control in endemic regions. These findings demonstrate the importance of vaccine strain matching with circulating field viruses and provide a framework for next-generation poultry vaccine development.
{"title":"Comparative efficacy of a field-strain matched bivalent inactivated vaccine against contemporary newcastle disease and infectious bronchitis viruses in Egypt","authors":"Ahmed A. Azab , Mahmoud Samir , Salah Zakaria , Hassna Maged , Nahed Yehia , Mohamed Taha , Ahmed A. El-Sanousi , Ahmed Aly Khalil","doi":"10.1016/j.vetimm.2025.111003","DOIUrl":"10.1016/j.vetimm.2025.111003","url":null,"abstract":"<div><h3>Background</h3><div>Newcastle disease virus (NDV) and infectious bronchitis virus (IBV) cause annual global economic losses exceeding $1 billion in the poultry industry. In Egypt remain major threats to poultry production. emerging variant strains increasingly challenge current vaccination strategies, necessitating more effective control measures.</div></div><div><h3>Methods</h3><div>We evaluated a novel bivalent inactivated vaccine (Valley Vac IB3 NDVg7) containing recent field isolates (NDV genotype VII and IBV variant-II) against a commercial bivalent vaccine. Seventy-one-day-old commercial chicks were randomized into seven groups (n = 10). Groups 1,4 and 2,5 received the novel and commercial vaccines respectively, while groups 3,6 served as unvaccinated controls, and group 7 as a negative control. At three weeks post-vaccination, groups were challenged with either NDV-B7-RLQP-CH-EG-12 or IBV-Eg/15170F-SP1/2015. Protection rates, viral shedding, ciliostasis, and immune responses were evaluated using standardized protocols.</div></div><div><h3>Results</h3><div>The novel vaccine demonstrated significantly superior protection (90–100 %, P < 0.01) compared to the commercial vaccine (60–70 %) against both viruses. Viral shedding in the novel vaccine group was reduced by 2.1 log10 (P < 0.001) by day 5 post-challenge, achieving complete clearance by day 7. Ciliostasis protection scores were significantly higher in the novel vaccine group (87.33–100) versus the commercial vaccine (35–78.33, P < 0.001). Serological responses showed stronger and more sustained antibody titers in the novel vaccine group for both NDV (8.0 ± 2.0 vs 6.7 ± 1.0 log₂, P < 0.01) and IBV (4612.6 ± 839.35 vs 3340.5 ± 1650.16 ELISA units, P < 0.01) through three weeks post-vaccination.</div></div><div><h3>Conclusions</h3><div>The novel bivalent vaccine incorporating contemporary field strains provided significantly enhanced protection against current NDV and IBV variants, offering a promising strategy for improved disease control in endemic regions. These findings demonstrate the importance of vaccine strain matching with circulating field viruses and provide a framework for next-generation poultry vaccine development.</div></div>","PeriodicalId":23511,"journal":{"name":"Veterinary immunology and immunopathology","volume":"288 ","pages":"Article 111003"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01Epub Date: 2025-09-11DOI: 10.1016/j.vetimm.2025.110998
Emad Abdel-Hamied , Shaimaa Kamel , Hanan E. Saeed
Background
The present study was undertaken to confirm the association between heat intolerance (HI) syndrome and FMD in cattle in Egypt, and to describe the clinical, hematological, biochemical and hormonal alterations, and expression of heat stress and chronic inflammatory related genes in cows in an attempt for understanding and explanation of the pathophysiological changes associated with HI following recovery from acute FMD.
Methods
Seventeen HI affected cows and 10 apparently healthy cows were involved in this work. Animals in the study were subjected to careful clinical examination. ELISA Assay was performed to confirm the previous affection of HI cows with FMD via demonstration of neutralizing antibodies to FMDV.
Results
Lack of tolerance to heat, panting, salivation, dry rough coat, debility, inadequate feeding, reduced milk yield were the most consistent clinical findings in HI cows. Cows with heat intolerance syndrome demonstrated a significant reduction (P < 0.05) in RBCs count, hemoglobin concentration. PCV, MCV and MCHC. There was a significant leukocytosis, neutrophilia, lymphopenia, eosinopenia, monocytopenia and thrombocytopenia in HI cows in comparison with control. Heat intolerance syndrome revealed non-significant change in serum activities of liver enzymes, total bilirubin, total proteins, albumin, glucose, serum creatinine, urea and BUN. However, the serum total lipids, total cholesterol, triglycerides and triiodothyronine (T3) were significantly decreased. While thyroxine (T4) and cortisol levels were significantly increased (P < 0.05) in HI cows in comparison with control healthy cows with controls. In addition to, upregulation of HSP70, HSP90, HSF, IL33 and CASP3 genes expression (P < 0.05).
Conclusion
Upregulated expression of heat shock and inflammatory genes and hormonal imbalance serve as good index for managing HI in endemic regions.
{"title":"Upregulation of heat stress and inflammatory genes expression, clinical and hemato- biochemical changes in cattle with heat intolerance syndrome following FMD infection in Egypt","authors":"Emad Abdel-Hamied , Shaimaa Kamel , Hanan E. Saeed","doi":"10.1016/j.vetimm.2025.110998","DOIUrl":"10.1016/j.vetimm.2025.110998","url":null,"abstract":"<div><h3>Background</h3><div>The present study was undertaken to confirm the association between heat intolerance (HI) syndrome and FMD in cattle in Egypt, and to describe the clinical, hematological, biochemical and hormonal alterations, and expression of heat stress and chronic inflammatory related genes in cows in an attempt for understanding and explanation of the pathophysiological changes associated with HI following recovery from acute FMD.</div></div><div><h3>Methods</h3><div>Seventeen HI affected cows and 10 apparently healthy cows were involved in this work. Animals in the study were subjected to careful clinical examination. ELISA Assay was performed to confirm the previous affection of HI cows with FMD via demonstration of neutralizing antibodies to FMDV.</div></div><div><h3>Results</h3><div>Lack of tolerance to heat, panting, salivation, dry rough coat, debility, inadequate feeding, reduced milk yield were the most consistent clinical findings in HI cows. Cows with heat intolerance syndrome demonstrated a significant reduction (P < 0.05) in RBCs count, hemoglobin concentration. PCV, MCV and MCHC. There was a significant leukocytosis, neutrophilia, lymphopenia, eosinopenia, monocytopenia and thrombocytopenia in HI cows in comparison with control. Heat intolerance syndrome revealed non-significant change in serum activities of liver enzymes, total bilirubin, total proteins, albumin, glucose, serum creatinine, urea and BUN. However, the serum total lipids, total cholesterol, triglycerides and triiodothyronine (T3) were significantly decreased. While thyroxine (T4) and cortisol levels were significantly increased (P < 0.05) in HI cows in comparison with control healthy cows with controls. In addition to, upregulation of <em>HSP70, HSP90, HSF, IL33 and CASP3</em> genes expression (P < 0.05).</div></div><div><h3>Conclusion</h3><div>Upregulated expression of heat shock and inflammatory genes and hormonal imbalance serve as good index for managing HI in endemic regions<strong>.</strong></div></div>","PeriodicalId":23511,"journal":{"name":"Veterinary immunology and immunopathology","volume":"288 ","pages":"Article 110998"},"PeriodicalIF":1.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-08-06DOI: 10.1016/j.vetimm.2025.110982
Sugandhika G. Welikadage , Habtamu B. Derseh , Trent Perry , Clare A. Anstead , Jean-Pierre Y. Scheerlinck , Vern M. Bowles
Breech strike is a major parasitic problem affecting wool-producing sheep. While skin wrinkles and fecal soiling are recognized risk factors, much of the difference in susceptibility between individual sheep remains unexplained. This study compared the early immune response of 3-year-old Merino ewes genetically selected to be resistant to breech strike to that of the non-selected ewes following a brief Lucilia cuprina larval challenge. Fourteen sheep (seven breech strike resistant and seven non-selected sheep) were challenged with L. cuprina eggs at four random sites on their back. Skin biopsies were collected 31 h post-implantation from the four infested and four mock sites (dental plugs without blow fly eggs) from each sheep and analysed using immunohistochemical staining for different cell biomarkers. A Milliplex ovine cytokine/chemokine assay was used to analyse the local cytokine response at these sites. An infiltration of leukocytes was observed at the larval feeding sites that predominantly comprised neutrophils. Significant increases in lymphocytes expressing T cell markers for CD4, CD1, CD8, T19, γδ-T cell, as well as the B cell marker CD45R, were observed compared to the mock sites. The pro-inflammatory cytokines IL-1α, IL-6, IL-17a, and chemoattractants including IL-8 and MIP-1α were significantly elevated in challenged sites. These results demonstrated a selective innate immune response in sheep following a brief larval challenge, which was similar in breech strike resistant and non-selected sheep, suggesting that the observed resistance to flystrike in the breech strike resistant flock is unlikely to be primarily mediated by local innate immune mechanisms at the tissue level.
{"title":"Characterising the innate immune response in breech strike resistant and non-selected sheep to the sheep blowfly (Lucilia cuprina)","authors":"Sugandhika G. Welikadage , Habtamu B. Derseh , Trent Perry , Clare A. Anstead , Jean-Pierre Y. Scheerlinck , Vern M. Bowles","doi":"10.1016/j.vetimm.2025.110982","DOIUrl":"10.1016/j.vetimm.2025.110982","url":null,"abstract":"<div><div>Breech strike is a major parasitic problem affecting wool-producing sheep. While skin wrinkles and fecal soiling are recognized risk factors, much of the difference in susceptibility between individual sheep remains unexplained. This study compared the early immune response of 3-year-old Merino ewes genetically selected to be resistant to breech strike to that of the non-selected ewes following a brief <em>Lucilia cuprina</em> larval challenge. Fourteen sheep (seven breech strike resistant and seven non-selected sheep) were challenged with <em>L. cuprina</em> eggs at four random sites on their back. Skin biopsies were collected 31 h post-implantation from the four infested and four mock sites (dental plugs without blow fly eggs) from each sheep and analysed using immunohistochemical staining for different cell biomarkers. A Milliplex ovine cytokine/chemokine assay was used to analyse the local cytokine response at these sites. An infiltration of leukocytes was observed at the larval feeding sites that predominantly comprised neutrophils. Significant increases in lymphocytes expressing T cell markers for CD4, CD1, CD8, T19, γδ-T cell, as well as the B cell marker CD45R<strong>,</strong> were observed compared to the mock sites. The pro-inflammatory cytokines IL-1α, IL-6, IL-17a, and chemoattractants including IL-8 and MIP-1α were significantly elevated in challenged sites. These results demonstrated a selective innate immune response in sheep following a brief larval challenge, which was similar in breech strike resistant and non-selected sheep, suggesting that the observed resistance to flystrike in the breech strike resistant flock is unlikely to be primarily mediated by local innate immune mechanisms at the tissue level.</div></div>","PeriodicalId":23511,"journal":{"name":"Veterinary immunology and immunopathology","volume":"287 ","pages":"Article 110982"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-08-05DOI: 10.1016/j.vetimm.2025.110980
Cagatay Esin, Busra Uzun
Feline Arterial Thromboembolism (FATE) is a challenging problem that requires urgent intervention. This study evaluated inflammatory markers' prognostic value in feline arterial thromboembolism (FATE), a devastating cardiac complication often necessitating euthanasia. We analysed inflammatory ratios (NLR, MLR, PLR, AISI, SIRI, SII) and echocardiographic measurements in FATE cats (n = 25) versus controls (n = 10). FATE patients demonstrated significantly elevated inflammatory markers and cardiac measurements. NLR showed strong correlation with cardiac parameters including LAMAX (r = 0.629), LA:Ao ratio (r = 0.489), IVSD (r = 0.422), and LVPWD (r = 0.607). Other inflammatory ratios similarly correlated with cardiac measurements. NLR emerged as the most accurate diagnostic biomarker (AUC = 1.000). Median survival time was 334 days overall. Cats with LAMAX >18 mm showed reduced survival (213 vs. 333 days). High NLR (>8) was associated with dramatically shortened survival (51 days) compared to moderate (5-8; 174 days) and low NLR (<5; 457 days). Elevated inflammatory markers (NLR >2, MLR >0.15, PLR >80, AISI >276, SIRI >1.08, SII >441) indicate poor prognosis. These accessible biomarkers may assist clinicians in emergency diagnosis confirmation and prognostication of FATE patients.
{"title":"Prognostic and diagnostic value of systemic inflammatory blood markers (NLR, MLR, PLR, AISI, SIRI, and SII) in feline arterial thromboembolism.","authors":"Cagatay Esin, Busra Uzun","doi":"10.1016/j.vetimm.2025.110980","DOIUrl":"10.1016/j.vetimm.2025.110980","url":null,"abstract":"<p><p>Feline Arterial Thromboembolism (FATE) is a challenging problem that requires urgent intervention. This study evaluated inflammatory markers' prognostic value in feline arterial thromboembolism (FATE), a devastating cardiac complication often necessitating euthanasia. We analysed inflammatory ratios (NLR, MLR, PLR, AISI, SIRI, SII) and echocardiographic measurements in FATE cats (n = 25) versus controls (n = 10). FATE patients demonstrated significantly elevated inflammatory markers and cardiac measurements. NLR showed strong correlation with cardiac parameters including LA<sub>MAX</sub> (r = 0.629), LA:Ao ratio (r = 0.489), IVSD (r = 0.422), and LVPWD (r = 0.607). Other inflammatory ratios similarly correlated with cardiac measurements. NLR emerged as the most accurate diagnostic biomarker (AUC = 1.000). Median survival time was 334 days overall. Cats with LA<sub>MAX</sub> >18 mm showed reduced survival (213 vs. 333 days). High NLR (>8) was associated with dramatically shortened survival (51 days) compared to moderate (5-8; 174 days) and low NLR (<5; 457 days). Elevated inflammatory markers (NLR >2, MLR >0.15, PLR >80, AISI >276, SIRI >1.08, SII >441) indicate poor prognosis. These accessible biomarkers may assist clinicians in emergency diagnosis confirmation and prognostication of FATE patients.</p>","PeriodicalId":23511,"journal":{"name":"Veterinary immunology and immunopathology","volume":"287 ","pages":"110980"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-08-06DOI: 10.1016/j.vetimm.2025.110983
Eun-Yeong Bok , Mooyoung Jung , Ui-Hyung Kim , Han Gyu Lee , Yoon Jung Do , Young-Bum Son , Yoonyoung Choi , Seungmin Ha
Aims
To evaluate the humoral immune response to the initial Lumpy skin disease (LSD) vaccination in three cattle breeds, namely Korean native cattle (Hanwoo), Holstein, and Jersey, up to 18 weeks post-vaccination.
Methods
Overall, 65 cattle were vaccinated with the live attenuated Neethling strain of the LSD vaccine (Lumpyvax®, MSD Animal Health). Antibody titers were measured using ELISA from blood samples collected before and at 3, 6, 9, 12, and 18 weeks post-vaccination. Pre-vaccination complete blood count parameters were analyzed to determine their correlation with antibody responses.
Results
Significant breed-specific differences were observed in antibody titers and seropositivity rates. Eighteen weeks post-vaccination, Holstein cattle exhibited the most significant increase in LSD antibody concentrations, followed by Hanwoo and Jersey cattle (p < 0.05). Additionally, Holstein cattle achieved the highest seroconversion rates (73.3 %), whereas Hanwoo cattle showed the lowest seropositivity (33.3 %) during the same period. Additionally, pre-vaccination immune cell profiles, particularly lymphocyte and basophil levels, were correlated with antibody responses, emphasizing the role of innate immunity in vaccine efficacy.
Conclusions
We should consider breed-specific immune responses and pre-vaccination immune cell profiles when developing vaccination strategies. Tailored approaches may enhance vaccine efficacy and improve disease control across different cattle breeds.
Clinical Relevance
We evaluated the antibody titers across different cattle breeds following LSD vaccination, providing critical insights into breed-specific vaccine efficacy. These findings support the development of tailored vaccination strategies, contributing to improved disease prevention, control measures, and overall livestock productivity.
{"title":"Breed-specific humoral immune responses to lumpy skin disease vaccination and its associated factors in cattle","authors":"Eun-Yeong Bok , Mooyoung Jung , Ui-Hyung Kim , Han Gyu Lee , Yoon Jung Do , Young-Bum Son , Yoonyoung Choi , Seungmin Ha","doi":"10.1016/j.vetimm.2025.110983","DOIUrl":"10.1016/j.vetimm.2025.110983","url":null,"abstract":"<div><h3>Aims</h3><div>To evaluate the humoral immune response to the initial Lumpy skin disease (LSD) vaccination in three cattle breeds, namely Korean native cattle (Hanwoo), Holstein, and Jersey, up to 18 weeks post-vaccination.</div></div><div><h3>Methods</h3><div>Overall, 65 cattle were vaccinated with the live attenuated Neethling strain of the LSD vaccine (Lumpyvax®, MSD Animal Health). Antibody titers were measured using ELISA from blood samples collected before and at 3, 6, 9, 12, and 18 weeks post-vaccination. Pre-vaccination complete blood count parameters were analyzed to determine their correlation with antibody responses.</div></div><div><h3>Results</h3><div>Significant breed-specific differences were observed in antibody titers and seropositivity rates. Eighteen weeks post-vaccination, Holstein cattle exhibited the most significant increase in LSD antibody concentrations, followed by Hanwoo and Jersey cattle (<em>p</em> < 0.05). Additionally, Holstein cattle achieved the highest seroconversion rates (73.3 %), whereas Hanwoo cattle showed the lowest seropositivity (33.3 %) during the same period. Additionally, pre-vaccination immune cell profiles, particularly lymphocyte and basophil levels, were correlated with antibody responses, emphasizing the role of innate immunity in vaccine efficacy.</div></div><div><h3>Conclusions</h3><div>We should consider breed-specific immune responses and pre-vaccination immune cell profiles when developing vaccination strategies. Tailored approaches may enhance vaccine efficacy and improve disease control across different cattle breeds.</div></div><div><h3>Clinical Relevance</h3><div>We evaluated the antibody titers across different cattle breeds following LSD vaccination, providing critical insights into breed-specific vaccine efficacy. These findings support the development of tailored vaccination strategies, contributing to improved disease prevention, control measures, and overall livestock productivity.</div></div>","PeriodicalId":23511,"journal":{"name":"Veterinary immunology and immunopathology","volume":"287 ","pages":"Article 110983"},"PeriodicalIF":1.4,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-07-04DOI: 10.1016/j.vetimm.2025.110974
Stacey C. Engel , Tanya J. Kerr , Gian D. van der Spuy , Tracey Jooste , Peter E. Buss , Jennifer L. Johns , Michele A. Miller , Léanie Kleynhans
Understanding immune responses to infectious diseases, such as tuberculosis (TB), is essential for developing diagnostic tests and studying disease progression. Although TB affects African savanna elephants (Loxodonta africana), few studies have investigated immune cells and function in this species, especially in the respiratory tract. Techniques for isolating immune cells from elephant bronchoalveolar lavage (BAL) samples have not been previously reported. Therefore, this study aimed to develop and optimise a protocol to isolate and characterise alveolar cell types in BAL fluid collected from free-ranging, African savanna elephants. The optimised protocol incorporated a mucin digestion step, filtration, Ficoll gradient separation and wash steps to remove contaminants and successfully isolate viable populations of alveolar mononuclear cells. The isolated cells were stained with Rapi-Diff and microscopically examined to differentiate and characterise each cell type present. Cells isolated from healthy African elephant BAL samples, using this method, were predominantly alveolar macrophages (92.5 – 100.0 %) followed by lymphocytes (0.0 – 6.0 %), neutrophils (0.0 – 3.0 %) and eosinophils (0.0 – 1.0 %). This study provides the first optimised protocol for the isolation of alveolar mononuclear cells for future investigations into local immune responses to respiratory diseases such as tuberculosis.
{"title":"Optimisation of bronchoalveolar lavage fluid preparation for mononuclear cell isolation and cytologic evaluation in free-ranging African elephants (Loxodonta africana)","authors":"Stacey C. Engel , Tanya J. Kerr , Gian D. van der Spuy , Tracey Jooste , Peter E. Buss , Jennifer L. Johns , Michele A. Miller , Léanie Kleynhans","doi":"10.1016/j.vetimm.2025.110974","DOIUrl":"10.1016/j.vetimm.2025.110974","url":null,"abstract":"<div><div>Understanding immune responses to infectious diseases, such as tuberculosis (TB), is essential for developing diagnostic tests and studying disease progression. Although TB affects African savanna elephants (<em>Loxodonta africana)</em>, few studies have investigated immune cells and function in this species, especially in the respiratory tract. Techniques for isolating immune cells from elephant bronchoalveolar lavage (BAL) samples have not been previously reported. Therefore, this study aimed to develop and optimise a protocol to isolate and characterise alveolar cell types in BAL fluid collected from free-ranging, African savanna elephants. The optimised protocol incorporated a mucin digestion step, filtration, Ficoll gradient separation and wash steps to remove contaminants and successfully isolate viable populations of alveolar mononuclear cells. The isolated cells were stained with Rapi-Diff and microscopically examined to differentiate and characterise each cell type present. Cells isolated from healthy African elephant BAL samples, using this method, were predominantly alveolar macrophages (92.5 – 100.0 %) followed by lymphocytes (0.0 – 6.0 %), neutrophils (0.0 – 3.0 %) and eosinophils (0.0 – 1.0 %). This study provides the first optimised protocol for the isolation of alveolar mononuclear cells for future investigations into local immune responses to respiratory diseases such as tuberculosis.</div></div>","PeriodicalId":23511,"journal":{"name":"Veterinary immunology and immunopathology","volume":"286 ","pages":"Article 110974"},"PeriodicalIF":1.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01Epub Date: 2025-08-05DOI: 10.1016/j.vetimm.2025.110981
Robson Sfaciotti Barducci , Anderson Aparecido Dias Santos , Letícia Graziele Pacheco , Thaila Cristina Putarov , João Fernando Albers Koch , Francine Carla Cadoná , Samay Zillmann Rocha Costa , Eduardo Kelm Battisti , Fernando Jonas Sutili
This study evaluated the effects of a β-glucan, proanthocyanidin, and saponin-based additive on growth performance, innate immunity, intestinal morphometry, water quality, and disease resistance in rainbow trout (Oncorhynchus mykiss). Experimental groups were designated GPS 1 (1.35 g/kg), GPS 2 (2.025 g/kg), and GPS 3 (2.7 g/kg) based on the additive’s key ingredients, with a non-supplemented control (CO) for comparison. Fish were fed these diets for 90 days. Fish fed GPS 2 exhibited significantly higher final weight, weight gain, and specific growth rate than CO. Plasma hemolytic activity (complement activity) was highest in GPS 1 and GPS 2. Lysozyme and myeloperoxidase activity were significantly greater in GPS 1. GPS 3 showed the highest superoxide anion production in blood leukocytes and elevated reactive oxygen species levels in plasma, but also the lowest free circulating DNA (dsDNA) concentrations. Intestinal morphometry analysis revealed greater villous height in GPS 1, followed by GPS 2, while villous density and total absorptive surface area were highest in GPS 2, followed by GPS 1. The intraepithelial lymphocyte score was significantly higher in GPS 3 than in CO. Water quality analysis showed significantly lower ammonia and nitrite levels in all supplemented groups after 48 h in a closed-system assay designed to evaluate nitrogenous waste accumulation. The bacterial challenge revealed higher survival rates in the supplemented groups (GPS 1: 95 %; GPS 2 and GPS 3: 100 %) compared to CO (70 %). In conclusion, GPS 2 provided the most balanced benefits, optimizing growth, immune response, intestinal integrity, and survival. GPS 3 appeared to induce a predominantly oxidative immune response, accompanied by an increase in intraepithelial lymphocyte density, suggesting enhanced mucosal immune activity. GPS 1 exhibited a robust immune response alongside improvements in intestinal histology. Overall, all three tested inclusion levels provided health and performance benefits when compared to the control group.
{"title":"Functional additive containing β-glucan, proanthocyanidins and saponins improves growth, immunity and gut health in rainbow trout","authors":"Robson Sfaciotti Barducci , Anderson Aparecido Dias Santos , Letícia Graziele Pacheco , Thaila Cristina Putarov , João Fernando Albers Koch , Francine Carla Cadoná , Samay Zillmann Rocha Costa , Eduardo Kelm Battisti , Fernando Jonas Sutili","doi":"10.1016/j.vetimm.2025.110981","DOIUrl":"10.1016/j.vetimm.2025.110981","url":null,"abstract":"<div><div>This study evaluated the effects of a β-glucan, proanthocyanidin, and saponin-based additive on growth performance, innate immunity, intestinal morphometry, water quality, and disease resistance in rainbow trout (<em>Oncorhynchus mykiss</em>). Experimental groups were designated GPS 1 (1.35 g/kg), GPS 2 (2.025 g/kg), and GPS 3 (2.7 g/kg) based on the additive’s key ingredients, with a non-supplemented control (CO) for comparison. Fish were fed these diets for 90 days. Fish fed GPS 2 exhibited significantly higher final weight, weight gain, and specific growth rate than CO. Plasma hemolytic activity (complement activity) was highest in GPS 1 and GPS 2. Lysozyme and myeloperoxidase activity were significantly greater in GPS 1. GPS 3 showed the highest superoxide anion production in blood leukocytes and elevated reactive oxygen species levels in plasma, but also the lowest free circulating DNA (dsDNA) concentrations. Intestinal morphometry analysis revealed greater villous height in GPS 1, followed by GPS 2, while villous density and total absorptive surface area were highest in GPS 2, followed by GPS 1. The intraepithelial lymphocyte score was significantly higher in GPS 3 than in CO. Water quality analysis showed significantly lower ammonia and nitrite levels in all supplemented groups after 48 h in a closed-system assay designed to evaluate nitrogenous waste accumulation. The bacterial challenge revealed higher survival rates in the supplemented groups (GPS 1: 95 %; GPS 2 and GPS 3: 100 %) compared to CO (70 %). In conclusion, GPS 2 provided the most balanced benefits, optimizing growth, immune response, intestinal integrity, and survival. GPS 3 appeared to induce a predominantly oxidative immune response, accompanied by an increase in intraepithelial lymphocyte density, suggesting enhanced mucosal immune activity. GPS 1 exhibited a robust immune response alongside improvements in intestinal histology. Overall, all three tested inclusion levels provided health and performance benefits when compared to the control group.</div></div>","PeriodicalId":23511,"journal":{"name":"Veterinary immunology and immunopathology","volume":"286 ","pages":"Article 110981"},"PeriodicalIF":1.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}