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Engineering an Fc-inert feline IgG1 by targeted mutations: Application to anti-PD-1 antibody development 通过靶向突变设计fc惰性猫IgG1:应用于抗pd -1抗体的开发。
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-10-01 Epub Date: 2025-09-15 DOI: 10.1016/j.vetimm.2025.111000
Shoma Nishibori , Yoshiho Takeda , Masaya Igase , Takuya Mizuno
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.
免疫检查点抑制剂(ICIs)已经彻底改变了人类的癌症治疗;然而,对ICIs在猫中的研究仍然有限,并且尚未对猫肿瘤疾病进行临床试验。本研究开发了一种针对猫PD-1分子的小鼠单克隆抗体(克隆1A1-2),并将1A1-2的恒定区替换为猫IgG1的恒定区,生成了小鼠-猫嵌合抗体(1A1-2- figg1)。然而,猫服用1A1-2-fIgG1可能会通过补体依赖性细胞毒性、抗体依赖性细胞介导的细胞毒性和抗体依赖性细胞吞噬作用消耗表达pd -1的效应t细胞,因为猫的IgG1与CD64、CD16和C1q结合。我们设计了两个1A1-2-fIgG1突变体,在恒定区域进行氨基酸替换,以减少Fc片段与C1q或Fcγ rs之间的相互作用,并减轻这些效应功能。这些突变成功地消除了与CD64、CD32和CD16的结合,同时保留了对FcRn的亲和力,这对于维持血液中抗体的半衰期至关重要。此外,突变体表现出与C1q的结合受损。尽管有这些修饰,突变抗体有效地恢复了受刺激淋巴细胞中PD-1/PD-L1信号抑制的IFN-γ产生,使其达到与原始抗体相当的水平。这些发现表明,工程抗体在未来的临床应用中具有潜在的猫肿瘤。
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引用次数: 0
Temporal changes in biomarkers of oxidative stress and inflammation in pigs after intravenous administration of E. coli lipopolysaccharide 静脉注射大肠杆菌脂多糖后猪氧化应激和炎症生物标志物的时间变化。
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-10-01 Epub Date: 2025-09-15 DOI: 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.
产肠毒素大肠杆菌感染是猪断奶后腹泻的主要原因,并与全身炎症和氧化应激有关。本研究旨在表征炎症和氧化应激生物标志物在响应大肠杆菌脂多糖(LPS)挑战时的时间变化,为宿主免疫反应提供见解。10头母猪(27.9 kg BW, ~ 3月龄)以低剂量(0.75 µg LPS/kg BW)或中等剂量(1.50 µg LPS/kg BW)注射大肠杆菌O111:B4衍生的LPS。分别于0(注射前)和0.5 ~ 72 h(注射LPS后)通过静脉导管采集血样13份。测量直肠温度、血液细胞因子、急性期蛋白和氧化应激标志物。采用半靶向代谢组学方法研究氧化应激标志物,包括8-iso-前列腺素F₂α (8-iso-PGF₂α)。直肠温度在3 h时达到峰值,在8 h时恢复到注射前水平。血浆c反应蛋白(CRP)在12 h达到峰值,而接触珠蛋白在24 h达到峰值。猪主要急性期蛋白(Pig- map)在24 h (LOW)和36 h (MODERATE)达到峰值。丙二醛(MDA)在0.5 ~ 1 h之间达到峰值,并在12 h内恢复到注射前水平。细胞因子IL-6、IFN-γ、IL-10和IL-1β在注射后1 ~ 3 h达到峰值。此外,皮质醇迅速升高,在2 h时达到峰值。这些发现表明,LPS刺激后炎症和氧化应激标志物的时间反应不同,支持它们作为评估干预措施调节猪感染诱导的氧化应激的潜在生物标志物。
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引用次数: 0
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 评价聚合抗原BLSOmp31在新型笼状颗粒佐剂(ISPA卵黄)中配制,经肠外或粘膜给药对公羊布鲁氏菌的疗效
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-10-01 Epub Date: 2025-09-05 DOI: 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.
鸡布鲁氏菌(B. ovis)是绵羊传染性附睾炎的病原,是全世界鸡群生殖障碍的主要原因。虽然减毒后的melitensis Rev.1菌株对该病原体具有异源保护作用,但它有重要的缺点。亚单位疫苗可以提供一种更安全的替代方案,考虑到“同一个健康”的做法。聚合体BLSOmp31先前被确定为对抗该病原体的保护性免疫原。在我们之前对BALB/c小鼠的研究中,我们评估了一种名为ISPA的新型笼状颗粒佐剂中配制的BLSOmp31的性能。在本研究中,我们使用了一种新的低成本ISPA变体ISPA蛋黄(BLSOmp31/ISPA蛋黄)配制的BLSOmp31。该制剂通过皮下和眼路给予公羊。我们评估了全身和粘膜免疫反应,并评估了其对鹅双球菌的保护能力。两种途径给药BLSOmp31/ISPA蛋黄均可诱导全身和可变粘膜IgG和IgA抗体应答,对血清学诊断无干扰。此外,该配方诱导了显著的特异性细胞免疫反应,并增加了外周血单核细胞中具有混合Th1/Th2谱的细胞因子基因的相对表达水平。虽然该疫苗不能预防实验感染B. ovis,但与通过眼路接种和未接种的公羊相比,经肠外免疫的公羊感染器官较少,生殖器官的组织病理学改变也较轻。相比之下,该制剂,无论是通过SC还是CONJ途径给药,都可以减少通过精液消除卵巢双球菌,并将感染传播的风险降至最低。
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引用次数: 0
Comparative efficacy of a field-strain matched bivalent inactivated vaccine against contemporary newcastle disease and infectious bronchitis viruses in Egypt 一种野毒株匹配二价灭活疫苗在埃及对现代新城疫和传染性支气管炎病毒的比较疗效。
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-10-01 Epub Date: 2025-09-16 DOI: 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.
背景:新城疫病毒(NDV)和传染性支气管炎病毒(IBV)每年给全球家禽业造成超过10亿美元的经济损失。在埃及,家禽生产仍然面临主要威胁。新出现的变异菌株日益挑战当前的疫苗接种策略,需要采取更有效的控制措施。方法:我们对一种新型二价灭活疫苗(谷Vac IB3 NDVg7)与一种市售二价疫苗进行了对比,该疫苗含有最新的野地分离株(NDV基因型VII和IBV变种- ii)。选用71日龄商品雏鸡,随机分为7组(n = 10)。1、4、2、5组分别接种新型疫苗和市售疫苗,3、6组为未接种对照组,7组为阴性对照组。接种疫苗后3周,各组分别接种NDV-B7-RLQP-CH-EG-12或IBV-Eg/15170F-SP1/2015。使用标准化方案评估保护率、病毒脱落、纤毛抑制和免疫反应。结果:新型疫苗具有显著的保护作用(90-100 %,P )。结论:采用现代田间毒株的新型二价疫苗可显著增强对当前NDV和IBV变体的保护作用,为改善流行地区的疾病控制提供了一种有希望的策略。这些发现证明了疫苗毒株与流行野地病毒匹配的重要性,并为下一代家禽疫苗的开发提供了框架。
{"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 ,&nbsp;Mahmoud Samir ,&nbsp;Salah Zakaria ,&nbsp;Hassna Maged ,&nbsp;Nahed Yehia ,&nbsp;Mohamed Taha ,&nbsp;Ahmed A. El-Sanousi ,&nbsp;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 &lt; 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 &lt; 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 &lt; 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 &lt; 0.01) and IBV (4612.6 ± 839.35 vs 3340.5 ± 1650.16 ELISA units, P &lt; 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}
引用次数: 0
Upregulation of heat stress and inflammatory genes expression, clinical and hemato- biochemical changes in cattle with heat intolerance syndrome following FMD infection in Egypt 埃及口蹄疫感染后热不耐受综合征牛的热应激和炎症基因表达上调、临床和血液生化变化
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-10-01 Epub Date: 2025-09-11 DOI: 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.
背景:本研究旨在证实埃及牛的热不耐受(HI)综合征与口蹄疫之间的关系,并描述奶牛的临床、血流变、生化和激素变化,以及热应激和慢性炎症相关基因的表达,以试图理解和解释急性口蹄疫恢复后与HI相关的病理生理变化。方法:选取17头HI病奶牛和10头表面健康奶牛。研究中的动物都接受了仔细的临床检查。采用酶联免疫吸附试验(ELISA),通过对口蹄疫病毒的中和抗体证实了HI奶牛先前对口蹄疫的影响。结果:热耐受不足、喘气、流涎、被毛干燥粗糙、虚弱、喂养不足、产奶量下降是HI奶牛最一致的临床表现。结论:热休克和炎症基因的表达上调以及激素失衡是流行地区控制HI的良好指标。
{"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 ,&nbsp;Shaimaa Kamel ,&nbsp;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 &lt; 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 &lt; 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 &lt; 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}
引用次数: 0
Characterising the innate immune response in breech strike resistant and non-selected sheep to the sheep blowfly (Lucilia cuprina) 抗臀击和非选择羊对羊蝇的先天免疫反应的特征
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-01 Epub Date: 2025-08-06 DOI: 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.
臀裂是影响产羊毛羊的主要寄生问题。虽然皮肤皱纹和粪便污染是公认的危险因素,但绵羊个体之间的易感性差异仍未得到解释。本研究比较了遗传选择的3岁美利奴母羊在短暂的铜露西莉亚幼虫攻击后的早期免疫反应与未选择的母羊的免疫反应。在14只羊(7只抗臀击羊和7只未选择的羊)背部的4个随机位置用铜乳杆菌卵攻卵。植入后31 h,从每只羊的4个感染部位和4个模拟部位(不含蝇卵的牙塞)采集皮肤活检,并使用免疫组织化学染色分析不同的细胞生物标志物。使用Milliplex羊细胞因子/趋化因子试验分析这些位点的局部细胞因子反应。在幼虫取食部位观察到白细胞的浸润,主要由中性粒细胞组成。淋巴细胞中表达T细胞标志物CD4、CD1、CD8、T19、γδ-T细胞以及B细胞标志物CD45R的数量明显高于模拟位点。促炎细胞因子IL-1α、IL-6、IL-17a和化学引诱剂IL-8、MIP-1α显著升高。这些结果表明,在短暂的幼虫攻击后,绵羊会产生选择性的先天免疫反应,这在臀击抵抗羊和非选择羊中是相似的,这表明在臀击抵抗羊中观察到的对蝇击的抗性不太可能主要由组织水平的局部先天免疫机制介导。
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引用次数: 0
Prognostic and diagnostic value of systemic inflammatory blood markers (NLR, MLR, PLR, AISI, SIRI, and SII) in feline arterial thromboembolism. 全身炎症血液标志物(NLR、MLR、PLR、AISI、SIRI和SII)在猫动脉血栓栓塞中的预后和诊断价值。
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-01 Epub Date: 2025-08-05 DOI: 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.

猫动脉血栓栓塞(FATE)是一个具有挑战性的问题,需要紧急干预。这项研究评估了炎症标志物在猫动脉血栓栓塞(FATE)中的预后价值,这是一种毁灭性的心脏并发症,通常需要安乐死。我们分析了FATE猫(n = 25)与对照组(n = 10)的炎症比率(NLR、MLR、PLR、AISI、SIRI、SII)和超声心动图测量结果。FATE患者表现出明显升高的炎症标志物和心脏测量。NLR与LAMAX (r = 0.629)、LA:Ao比(r = 0.489)、IVSD (r = 0.422)、LVPWD (r = 0.607)有较强的相关性。其他炎症比率也与心脏测量结果相似。NLR成为最准确的诊断生物标志物(AUC = 1.000)。中位生存时间为334天。使用LAMAX >18 mm的猫存活时间缩短(213天对333天)。与中度NLR (5-8;低NLR (2, MLR >0.15, PLR >80, AISI >276, SIRI >1.08, SII >441)提示预后不良。这些可获得的生物标志物可帮助临床医生对FATE患者进行紧急诊断、确认和预测。
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引用次数: 0
Breed-specific humoral immune responses to lumpy skin disease vaccination and its associated factors in cattle 牛瘤状皮肤病疫苗接种对品种特异性体液免疫反应及其相关因素
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-01 Epub Date: 2025-08-06 DOI: 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.
目的评价三个牛品种,即韩国本土牛(Hanwoo)、荷斯坦牛和泽西牛,在接种后18周内对最初的肿块性皮肤病(LSD)疫苗的体液免疫反应。方法选用65头牛接种LSD疫苗(Lumpyvax®,MSD Animal Health)的针刺减毒活株。在接种前和接种后3、6、9、12和18周采集血液样本,采用ELISA法测定抗体滴度。分析接种前全血细胞计数参数以确定其与抗体反应的相关性。结果在抗体滴度和血清阳性率方面存在明显的品种特异性差异。接种18周后,荷斯坦牛的LSD抗体浓度升高最为显著,其次是韩宇牛和泽西牛(p <; 0.05)。此外,在同一时期,荷斯坦牛的血清转化率最高(73.3 %),而韩宇牛的血清阳性率最低(33.3% %)。此外,接种前免疫细胞谱,特别是淋巴细胞和嗜碱性粒细胞水平,与抗体反应相关,强调了先天免疫在疫苗效力中的作用。结论在制定疫苗接种策略时应考虑品种特异性免疫反应和疫苗接种前免疫细胞谱。量身定制的方法可以提高疫苗效力,改善不同牛品种的疾病控制。临床相关性我们评估了不同牛品种接种LSD后的抗体滴度,为品种特异性疫苗的有效性提供了重要见解。这些发现支持制定有针对性的疫苗接种战略,有助于改善疾病预防、控制措施和整体牲畜生产力。
{"title":"Breed-specific humoral immune responses to lumpy skin disease vaccination and its associated factors in cattle","authors":"Eun-Yeong Bok ,&nbsp;Mooyoung Jung ,&nbsp;Ui-Hyung Kim ,&nbsp;Han Gyu Lee ,&nbsp;Yoon Jung Do ,&nbsp;Young-Bum Son ,&nbsp;Yoonyoung Choi ,&nbsp;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> &lt; 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}
引用次数: 0
Optimisation of bronchoalveolar lavage fluid preparation for mononuclear cell isolation and cytologic evaluation in free-ranging African elephants (Loxodonta africana) 自由放养非洲象支气管肺泡灌洗液制备单核细胞分离及细胞学评价的优化
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-08-01 Epub Date: 2025-07-04 DOI: 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.
了解对传染病(如结核病)的免疫反应对于开发诊断测试和研究疾病进展至关重要。尽管结核病影响非洲草原象(Loxodonta africana),但很少有研究调查该物种的免疫细胞和功能,特别是呼吸道的免疫细胞和功能。从大象支气管肺泡灌洗液(BAL)样本中分离免疫细胞的技术以前没有报道。因此,本研究旨在开发和优化一种方案,以分离和表征从自由放养的非洲稀树草原象收集的BAL液中的肺泡细胞类型。优化的方案包括粘蛋白消化步骤,过滤,菲科尔梯度分离和洗涤步骤,以去除污染物,并成功分离肺泡单核细胞的活菌群。将分离的细胞用Rapi-Diff染色,并在显微镜下观察每种细胞类型的分化和特征。用这种方法从健康非洲象BAL样本中分离的细胞主要是肺泡巨噬细胞(92.5 ~ 100.0 %),其次是淋巴细胞(0.0 ~ 6.0 %)、中性粒细胞(0.0 ~ 3.0 %)和嗜酸性粒细胞(0.0 ~ 1.0 %)。这项研究为肺泡单核细胞的分离提供了第一个优化的方案,用于未来对呼吸系统疾病(如结核病)局部免疫反应的研究。
{"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 ,&nbsp;Tanya J. Kerr ,&nbsp;Gian D. van der Spuy ,&nbsp;Tracey Jooste ,&nbsp;Peter E. Buss ,&nbsp;Jennifer L. Johns ,&nbsp;Michele A. Miller ,&nbsp;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}
引用次数: 0
Functional additive containing β-glucan, proanthocyanidins and saponins improves growth, immunity and gut health in rainbow trout 含有β-葡聚糖、原花青素和皂苷的功能性添加剂促进虹鳟鱼生长、免疫和肠道健康
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-08-01 Epub Date: 2025-08-05 DOI: 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.
本研究评估了β-葡聚糖、原花青素和皂素添加剂对虹鳟生长性能、先天免疫、肠道形态、水质和抗病性的影响。根据添加剂的关键成分选择GPS 1(1.35 g/kg)、GPS 2(2.025 g/kg)和GPS 3(2.7 g/kg)试验组,并以不添加CO作为对照。饲喂这些饲料90天。饲用GPS 2的鱼的最终体重、增重和特定生长率均显著高于饲用CO。血浆溶血活性(补体活性)以GPS 1和GPS 2最高。溶菌酶和髓过氧化物酶活性显著高于gps1。GPS 3显示出血液白细胞超氧阴离子产量最高,血浆活性氧水平升高,但游离循环DNA (dsDNA)浓度最低。肠道形态分析显示,GPS 1组的绒毛高度最高,GPS 2组次之,GPS 2组的绒毛密度和总吸收表面积最高,GPS 1组次之。在GPS 3中,上皮内淋巴细胞评分显著高于CO。水质分析显示,在48 h后,所有补充组的氨和亚硝酸盐水平均显著降低。细菌攻击显示,补充组的存活率更高(GPS 1:95 %;GPS 2和GPS 3: 100 %)与CO(70 %)相比。综上所述,GPS 2提供了最平衡的效益,优化了生长、免疫反应、肠道完整性和生存。GPS 3似乎诱导了主要的氧化免疫反应,并伴有上皮内淋巴细胞密度的增加,表明粘膜免疫活性增强。GPS 1在肠道组织学改善的同时表现出强大的免疫反应。总的来说,与对照组相比,所有三个测试的纳入水平都提供了健康和性能方面的好处。
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引用次数: 0
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Veterinary immunology and immunopathology
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