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Expanding tropism: Avian B cells as novel cellular target of infectious bronchitis virus 趋向性扩展:禽B细胞是传染性支气管炎病毒的新细胞靶点。
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-18 DOI: 10.1016/j.vetimm.2025.111005
Sufna M. Suhail, Motamed E. Mahmoud, Ishara M. Isham, Ahmed Ali, Muhammad Farooq, Anne Shehara Perera, Lahiru W. Waduge, Luke Xiu, Susan C. Cork, Ashish Gupta, Mohamed Faizal Abdul-Careem
Infectious bronchitis virus (IBV) causes infectious bronchitis (IB), which is a major concern for the global poultry industry as a result of substantial economic losses. Although epithelial cells were described as the primary target cells of IBV, other susceptible cell types including macrophages and monocytes, have been identified, where productive infection impairs cellular functions. Avian B cells are central to antibody-mediated immunity in chickens against pathogens, including IBV; however, it remains unknown if IBV can infect and replicate in B cells. This study investigated whether Delmarva (DMV)/1639 IBV can infect B cells in the bursa of Fabricius (BF) in vivo and in DT–40 cells in vitro. In vivo, a significantly higher viral genome load was observed in the BF at 3 days post-infection (dpi), with similar result in sorted B cells from the BF. Viral RNA was found to be localized within B cells of the BF using an in situ hybridization combined with immunohistochemistry. In vitro, a comparable trend in viral genome load was observed in infected DT–40 cells and culture supernatants up to 72 h post-infection (hpi). Immunofluorescence assay revealed a significantly higher percentage of DT–40 cells expressing IBV nucleoprotein. Inoculation of DT-40 cells with virus-containing supernatant confirmed infectivity as did inoculation of embryonated eggs, which resulted in IBV-specific lesions including dwarfing and stunting. These findings demonstrate that IBV can infect and replicate productively in avian B cells; however further studies are warranted to elucidate the impact of IBV infection on B cell function and its role in disease pathogenesis.
传染性支气管炎病毒(IBV)引起传染性支气管炎(IB),这是全球家禽业关注的一个主要问题,造成了巨大的经济损失。虽然上皮细胞被描述为IBV的主要靶细胞,但其他易感细胞类型,包括巨噬细胞和单核细胞,已被确定,其中生产性感染损害细胞功能。禽B细胞是鸡对病原体(包括IBV)的抗体介导免疫的核心;然而,IBV是否能感染B细胞并在B细胞中复制尚不清楚。本实验研究了Delmarva (DMV)/1639 IBV是否能在体内感染法氏囊(BF) B细胞,并在体外感染DT-40细胞。在体内,在感染后3天(dpi), BF中观察到明显更高的病毒基因组载量,从BF中分类的B细胞也有类似的结果。利用原位杂交结合免疫组化技术,发现病毒RNA在BF的B细胞内定位。在体外,在感染后72 h (hpi)感染的DT-40细胞和培养上清中观察到病毒基因组负荷的类似趋势。免疫荧光分析显示,表达IBV核蛋白的DT-40细胞比例显著提高。用含病毒的上清液接种DT-40细胞证实了感染能力,接种胚卵也证实了感染能力,导致ibv特异性病变,包括矮化和发育迟缓。这些结果表明,IBV可以感染并在禽B细胞中高效复制;然而,IBV感染对B细胞功能的影响及其在疾病发病机制中的作用有待进一步研究。
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引用次数: 0
A DIVA-compatible Mycobacterium bovis triple mutant vaccine confers protection against bovine tuberculosis in mouse model 一种diva兼容的牛分枝杆菌三突变疫苗在小鼠模型中对牛结核病具有保护作用
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-17 DOI: 10.1016/j.vetimm.2025.111001
Federico Carlos Blanco , Renée Onnainty , María Rocío Marini , Laura Inés Klepp , Rosana Valeria Rocha , Luciana Andrea Villafañe , Cristina Lourdes Vazquez , Ana Canal , Gladys Granero , Fabiana Bigi
Bovine tuberculosis (bTB) is a pulmonary infectious disease caused by Mycobacterium bovis, affecting cattle and a wide range of mammals, including humans. Despite its significant impact on global livestock production, no commercial vaccine is currently available, partly due to potential interference with standard diagnostic tests. In this study, we evaluated the protective efficacy of a triple M. bovis mutant lacking the immunodominant antigens ESAT-6 and CFP-10, as well as the virulence factor Ag85A. This mutant is compatible with DIVA (Differentiation of Infected from Vaccinated Animals) diagnostics based on ESAT-6 and CFP-10 detection. The triple mutant was assayed both alone and in a heterologous prime-boost regimen using recombinant Ag85A conjugated to chitosan nanocapsules. Protection was assessed by quantifying M. bovis colony-forming units (CFUs) in the lungs and spleen following challenge. Organ homogenates were cultured on solid media, and CFUs were enumerated at five and ten weeks post-plating. At five weeks, all vaccinated groups demonstrated comparable protection in the lungs. In the spleen, both the triple mutant and BCG groups showed reduced CFU counts compared to the unvaccinated group. By ten weeks, lung protection was most pronounced in the prime-boost and BCG groups, whereas spleen protection was restricted to the prime-boost group. At this stage, persistence of the triple mutant was detected in both lungs and spleen, highlighting the need for further evaluation of its residual virulence. Post-challenge immune responses were assessed by measuring CD4 +KLRG1-CXCL3 + T cells, a subset previously associated with protective immunity against tuberculosis, among other T cell populations evaluated. Vaccinated mice exhibited a significant expansion of this population compared to unvaccinated controls. Notably, higher frequencies of these cells correlated with reduced pulmonary bacterial burden, reinforcing their potential as a biomarker of protective immunity.
牛结核病(bTB)是一种由牛分枝杆菌引起的肺部传染病,影响牛和包括人类在内的多种哺乳动物。尽管它对全球畜牧业生产产生重大影响,但目前还没有商用疫苗,部分原因是标准诊断测试可能受到干扰。在这项研究中,我们评估了缺乏免疫优势抗原ESAT-6和CFP-10以及毒力因子Ag85A的三种牛分枝杆菌突变体的保护效果。该突变体与基于ESAT-6和CFP-10检测的DIVA(受感染动物与接种动物的区分)诊断兼容。利用重组Ag85A偶联壳聚糖纳米胶囊对三突变体进行了单独和异源启动-增强方案的检测。通过对肺部和脾脏中的牛支原体集落形成单位(cfu)进行量化来评估保护作用。在固体培养基上培养器官匀浆,并在镀后5周和10周枚举cfu。在五周时,所有接种组的肺部都显示出相当的保护作用。在脾脏中,与未接种疫苗组相比,三重突变组和卡介苗组均显示CFU计数减少。到第10周时,肺保护在初始强化组和卡介苗组最为明显,而脾脏保护仅限于初始强化组。在这个阶段,在肺和脾脏中检测到三重突变体的持久性,强调需要进一步评估其残留毒力。通过测量CD4 +KLRG1-CXCL3 + T细胞(先前与结核病保护性免疫相关的一个亚群)和其他评估的T细胞群来评估攻击后免疫应答。与未接种疫苗的对照组相比,接种疫苗的小鼠表现出显著的种群扩张。值得注意的是,这些细胞的高频率与肺部细菌负荷的减少相关,增强了它们作为保护性免疫生物标志物的潜力。
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引用次数: 0
A DIVA-compatible Mycobacterium bovis triple mutant vaccine confers protection against bovine tuberculosis in mouse model 一种diva兼容的牛分枝杆菌三突变疫苗在小鼠模型中对牛结核病具有保护作用
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-17 DOI: 10.1016/j.vetimm.2025.111001
Federico Carlos Blanco , Renée Onnainty , María Rocío Marini , Laura Inés Klepp , Rosana Valeria Rocha , Luciana Andrea Villafañe , Cristina Lourdes Vazquez , Ana Canal , Gladys Granero , Fabiana Bigi
Bovine tuberculosis (bTB) is a pulmonary infectious disease caused by Mycobacterium bovis, affecting cattle and a wide range of mammals, including humans. Despite its significant impact on global livestock production, no commercial vaccine is currently available, partly due to potential interference with standard diagnostic tests. In this study, we evaluated the protective efficacy of a triple M. bovis mutant lacking the immunodominant antigens ESAT-6 and CFP-10, as well as the virulence factor Ag85A. This mutant is compatible with DIVA (Differentiation of Infected from Vaccinated Animals) diagnostics based on ESAT-6 and CFP-10 detection. The triple mutant was assayed both alone and in a heterologous prime-boost regimen using recombinant Ag85A conjugated to chitosan nanocapsules. Protection was assessed by quantifying M. bovis colony-forming units (CFUs) in the lungs and spleen following challenge. Organ homogenates were cultured on solid media, and CFUs were enumerated at five and ten weeks post-plating. At five weeks, all vaccinated groups demonstrated comparable protection in the lungs. In the spleen, both the triple mutant and BCG groups showed reduced CFU counts compared to the unvaccinated group. By ten weeks, lung protection was most pronounced in the prime-boost and BCG groups, whereas spleen protection was restricted to the prime-boost group. At this stage, persistence of the triple mutant was detected in both lungs and spleen, highlighting the need for further evaluation of its residual virulence. Post-challenge immune responses were assessed by measuring CD4 +KLRG1-CXCL3 + T cells, a subset previously associated with protective immunity against tuberculosis, among other T cell populations evaluated. Vaccinated mice exhibited a significant expansion of this population compared to unvaccinated controls. Notably, higher frequencies of these cells correlated with reduced pulmonary bacterial burden, reinforcing their potential as a biomarker of protective immunity.
牛结核病(bTB)是一种由牛分枝杆菌引起的肺部传染病,影响牛和包括人类在内的多种哺乳动物。尽管它对全球畜牧业生产产生重大影响,但目前还没有商用疫苗,部分原因是标准诊断测试可能受到干扰。在这项研究中,我们评估了缺乏免疫优势抗原ESAT-6和CFP-10以及毒力因子Ag85A的三种牛分枝杆菌突变体的保护效果。该突变体与基于ESAT-6和CFP-10检测的DIVA(受感染动物与接种动物的区分)诊断兼容。利用重组Ag85A偶联壳聚糖纳米胶囊对三突变体进行了单独和异源启动-增强方案的检测。通过对肺部和脾脏中的牛支原体集落形成单位(cfu)进行量化来评估保护作用。在固体培养基上培养器官匀浆,并在镀后5周和10周枚举cfu。在五周时,所有接种组的肺部都显示出相当的保护作用。在脾脏中,与未接种疫苗组相比,三重突变组和卡介苗组均显示CFU计数减少。到第10周时,肺保护在初始强化组和卡介苗组最为明显,而脾脏保护仅限于初始强化组。在这个阶段,在肺和脾脏中检测到三重突变体的持久性,强调需要进一步评估其残留毒力。通过测量CD4 +KLRG1-CXCL3 + T细胞(先前与结核病保护性免疫相关的一个亚群)和其他评估的T细胞群来评估攻击后免疫应答。与未接种疫苗的对照组相比,接种疫苗的小鼠表现出显著的种群扩张。值得注意的是,这些细胞的高频率与肺部细菌负荷的减少相关,增强了它们作为保护性免疫生物标志物的潜力。
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引用次数: 0
GM-CSF-adjuvanted Newcastle disease virus-vectored bivalent vaccine elicits enhanced dual immunity against Newcastle disease and infectious bursal disease in chickens gm - csf佐剂的新城疫病毒载体二价疫苗增强了鸡对新城疫和传染性法氏囊病的双重免疫。
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-16 DOI: 10.1016/j.vetimm.2025.111002
Qing Wu , Jinmiao Liu , Weiyue Cao , Jiaxin Li , Huimin Li , Yuhan Jin , Zhitong Li , Xinyu Li , Wenying Sun , Lin Bai , Xinyuan Shen , Xiaochen Guo , Guiping Ren
Infectious bursal disease (IBD) and Newcastle disease (ND) are major infectious diseases that endanger poultry. Despite current vaccination efforts, both diseases still occur worldwide. We have developed bivalent vaccines capable of simultaneously preventing ND and IBD, which does not produce mutant IBDV. Using reverse genetics, we constructed a recombinant Newcastle disease virus (NDV) vector based on the common vaccine strain Clone30 to express the host-protective immunogen VP2L of the IBDV strain and chicken granulocyte-macrophage colony-stimulating factor (GM-CSF). The IBDV-encoded VP2L protein and chicken GM-CSF gene were inserted into different positions of the NDV full-length cDNA in various forms to achieve high-level expression. We successfully rescued the ND-AI bivalent vaccines (rClone30-VP2L(P/M)-GM-CSF(P/M), rClone30-VP2L(NP)-GM-CSF(P/M), rClone30-VP2L(P/M)-GM-CSF(NP) and rClone30-VP2L-IRES-GM-CSF(P/M)). The ND-AI bivalent vaccines maintained genetic stability after at least three consecutive passages in chicken embryos and was confirmed to express VP2L and GM-CSF proteins. The replication titers of the ND-AI bivalent vaccines in chicken embryos and cell cultures were comparable to those of the parental NDV strain rClone30. To assess the immunogenicity of the ND-AI bivalent vaccines, it was administered to 14-day-old commercial chicken chicks, and immune responses were continuously monitored for four weeks post-vaccination. By day 10 post-vaccination, the hemagglutination inhibition (HI) antibody titers of the recombinant NDV vaccine had far exceeded the theoretical protective threshold (4 log2) and remained at high levels for 28 days. Additionally, the levels of IBDV-specific antibodies in the ND-AI bivalent vaccines rapidly increased and remained at high titers for 14 days. Concurrently, the proliferation responses of B cells, CD4 + , and CD8 + T cells were enhanced, and the protein expression levels and mRNA transcription levels of inflammatory factors significantly increased. In summary, the ND-AI bivalent vaccines can stimulate the body to produce a stronger immune response, demonstrating its potential as a vaccine for IBD and ND. Additionally, the addition of GM-CSF can further enhance the immune response.
传染性法氏囊病(IBD)和新城疫(ND)是危害家禽的主要传染病。尽管目前努力接种疫苗,但这两种疾病仍在世界范围内发生。我们已经开发出能够同时预防ND和IBD的二价疫苗,它不会产生突变型IBDV。以新城疫病毒(NDV)常见疫苗株克隆30为基础,利用反向遗传学技术构建了重组新城疫病毒(NDV)载体,表达了新城疫病毒(IBDV)的宿主保护免疫原VP2L和鸡粒细胞-巨噬细胞集落刺激因子(GM-CSF)。将ibdv编码的VP2L蛋白和鸡GM-CSF基因以不同形式插入NDV全长cDNA的不同位置,实现高水平表达。我们成功拯救了ND-AI双价疫苗(rClone30-VP2L(P/M)-GM-CSF(P/M)、rClone30-VP2L(NP)-GM-CSF(P/M)、rClone30-VP2L(P/M)-GM-CSF(NP)和rClone30-VP2L- ires -GM-CSF(P/M))。ND-AI二价疫苗在鸡胚中至少连续传代三次后保持遗传稳定性,并被证实表达VP2L和GM-CSF蛋白。ND-AI二价疫苗在鸡胚和细胞培养物中的复制滴度与亲本NDV菌株rClone30相当。为了评估ND-AI二价疫苗的免疫原性,将其接种给14日龄的商品雏鸡,并在接种后4周内连续监测免疫反应。接种后第10天,重组新城疫疫苗的血凝抑制(HI)抗体滴度远远超过理论保护阈值(4 log2),并在28天内保持高水平。此外,ND-AI二价疫苗中ibdv特异性抗体的水平迅速上升,并在14天内保持高滴度。同时,B细胞、CD4 + 、CD8 + T细胞的增殖反应增强,炎症因子蛋白表达水平和mRNA转录水平显著升高。总之,ND- ai二价疫苗可刺激机体产生更强的免疫反应,显示其作为IBD和ND疫苗的潜力。此外,GM-CSF的加入可以进一步增强免疫应答。
{"title":"GM-CSF-adjuvanted Newcastle disease virus-vectored bivalent vaccine elicits enhanced dual immunity against Newcastle disease and infectious bursal disease in chickens","authors":"Qing Wu ,&nbsp;Jinmiao Liu ,&nbsp;Weiyue Cao ,&nbsp;Jiaxin Li ,&nbsp;Huimin Li ,&nbsp;Yuhan Jin ,&nbsp;Zhitong Li ,&nbsp;Xinyu Li ,&nbsp;Wenying Sun ,&nbsp;Lin Bai ,&nbsp;Xinyuan Shen ,&nbsp;Xiaochen Guo ,&nbsp;Guiping Ren","doi":"10.1016/j.vetimm.2025.111002","DOIUrl":"10.1016/j.vetimm.2025.111002","url":null,"abstract":"<div><div>Infectious bursal disease (IBD) and Newcastle disease (ND) are major infectious diseases that endanger poultry. Despite current vaccination efforts, both diseases still occur worldwide. We have developed bivalent vaccines capable of simultaneously preventing ND and IBD, which does not produce mutant IBDV. Using reverse genetics, we constructed a recombinant Newcastle disease virus (NDV) vector based on the common vaccine strain Clone30 to express the host-protective immunogen VP2L of the IBDV strain and chicken granulocyte-macrophage colony-stimulating factor (GM-CSF). The IBDV-encoded VP2L protein and chicken GM-CSF gene were inserted into different positions of the NDV full-length cDNA in various forms to achieve high-level expression. We successfully rescued the ND-AI bivalent vaccines (rClone30-VP2L(P/M)-GM-CSF(P/M), rClone30-VP2L(NP)-GM-CSF(P/M), rClone30-VP2L(P/M)-GM-CSF(NP) and rClone30-VP2L-IRES-GM-CSF(P/M)). The ND-AI bivalent vaccines maintained genetic stability after at least three consecutive passages in chicken embryos and was confirmed to express VP2L and GM-CSF proteins. The replication titers of the ND-AI bivalent vaccines in chicken embryos and cell cultures were comparable to those of the parental NDV strain rClone30. To assess the immunogenicity of the ND-AI bivalent vaccines, it was administered to 14-day-old commercial chicken chicks, and immune responses were continuously monitored for four weeks post-vaccination. By day 10 post-vaccination, the hemagglutination inhibition (HI) antibody titers of the recombinant NDV vaccine had far exceeded the theoretical protective threshold (4 log2) and remained at high levels for 28 days. Additionally, the levels of IBDV-specific antibodies in the ND-AI bivalent vaccines rapidly increased and remained at high titers for 14 days. Concurrently, the proliferation responses of B cells, CD4 + , and CD8 + T cells were enhanced, and the protein expression levels and mRNA transcription levels of inflammatory factors significantly increased. In summary, the ND-AI bivalent vaccines can stimulate the body to produce a stronger immune response, demonstrating its potential as a vaccine for IBD and ND. Additionally, the addition of GM-CSF can further enhance the immune response.</div></div>","PeriodicalId":23511,"journal":{"name":"Veterinary immunology and immunopathology","volume":"288 ","pages":"Article 111002"},"PeriodicalIF":1.4,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092541","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
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 : 2025-09-16 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。
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引用次数: 0
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 : 2025-09-15 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 : 2025-09-15 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
Post-vaccination sero-monitoring of bovine calves in Indian subcontinent: A review on progress towards brucellosis control 印度次大陆小牛疫苗接种后血清监测:布鲁氏菌病控制进展综述
IF 1.4 3区 农林科学 Q4 IMMUNOLOGY Pub Date : 2025-09-12 DOI: 10.1016/j.vetimm.2025.110999
Rajeswari Shome, Prabhakar Yellanur Konda, Shanmugam Gandu, Somy Skariah, Praveen Kumar Attiganahalli Muninarayanaswamy, Snigdha Madhaba Maharana, Nagalingam Mohandoss
Brucellosis caused by Brucella abortus remains a major zoonotic challenge in India, causing substantial economic losses in livestock and public health risks. Although India has implemented nationwide S19 vaccination in cattle and buffaloes, comprehensive evaluation of its effectiveness across different regions and between species has been lacking. This study sought to assess post-vaccination sero-conversion rates in calves of aged 4–8 months across five Indian states/union territories (UTs), examine species-specific differences in vaccine response between cattle and buffaloes, and generate practical recommendations to optimize the national brucellosis control program. A multi-phase sero-monitoring study analyzed 19,893 serum samples, comprising 16,085 cattle calves and 3609 buffalo calves during 2021–2024. The samples were collected from Andhra Pradesh, Chandigarh, Haryana, Odisha, and Tamil Nadu and tested using laboratory standardized indirect enzyme-linked immunosorbent assay (iELISA).Significant disparities were observed between species with overall sero-conversion rates of 75.87 % in cattle versus 67.22 % in buffaloes (p < 0.001). Tamil Nadu demonstrated exceptional performance (84.61 %; 95 % CI: 84.20–84.95), with districts like Namakkal achieving 100 % sero-conversion. Other regions showed varied efficacy: Chandigarh (80.77 %), Andhra Pradesh (69.52 %), and Haryana (69.43 %) consistently exhibited 10–15 % lower rates in buffaloes (p < 0.001). Odisha displayed notable phase-wise improvement (71.84 %; CI: 70.02–71.12), with Jagatsinghpur district reaching 97.85 % and buffalo calves improving from 17.64 % (Phase I) to 57.5 %. While, the S19 program achieves moderate efficacy but highlights species-specific disparities and replicable success models such as Tamil Nadu. Targeted buffalo vaccination strategies and adoption of best practices are recommended to achieve > 80 % vaccination coverage thereby herd immunity. Overall, this study provides an evidence-based framework for strengthening India’s brucellosis control program and contributing to global eradication efforts.
流产布鲁氏菌引起的布鲁氏菌病仍然是印度人畜共患疾病的一个主要挑战,造成牲畜方面的重大经济损失和公共卫生风险。尽管印度在全国范围内对牛和水牛实施了S19疫苗接种,但缺乏对其在不同地区和物种之间的有效性的全面评估。本研究旨在评估印度5个邦/联邦属地(ut) 4-8个月犊牛接种疫苗后的血清转化率,检查牛和水牛之间疫苗反应的物种特异性差异,并为优化国家布鲁氏菌病控制规划提出实用建议。一项多阶段血清监测研究分析了19893份血清样本,其中包括2021-2024年期间的16085头小牛和3609头水牛。样本采集自安得拉邦、昌迪加尔、哈里亚纳邦、奥里萨邦和泰米尔纳德邦,并使用实验室标准化间接酶联免疫吸附法(iELISA)进行检测。不同种属之间存在显著差异,牛的血清总转化率为75.87 %,而水牛为67.22 % (p  80 %,即群体免疫接种覆盖率)。总的来说,这项研究为加强印度的布鲁氏菌病控制规划和促进全球根除工作提供了一个基于证据的框架。
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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 : 2025-09-11 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。
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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 : 2025-09-05 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
期刊
Veterinary immunology and immunopathology
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