Advances in FIV vaccine technology

Advances in vaccine technology are occurring in the molecular techniques used to develop vaccines and in the assessment of vaccine efficacy, allowing more complete characterization of vaccine-induced immunity correlating to protection. FIV vaccine development has closely mirrored and occasionally surpassed the development of HIV-1 vaccine, leading to first licensed technology. This review will discuss technological advances in vaccine designs, challenge infection assessment, and characterization of vaccine immunity in the context of the protection detected with prototype and commercial dual-subtype FIV vaccines and in relation to HIV-1.     

Bovine leukemia virus: A major silent threat to proper immune responses in cattle

Bovine leukemia virus (BLV) infection is widespread in the US dairy industry and the majority of producers do not actively try to manage or reduce BLV incidence within their herds. However, BLV is estimated to cost the dairy industry hundreds of millions of dollars annually and this is likely a conservative estimate. BLV is not thought to cause animal distress or serious pathology unless infection progresses to leukemia or lymphoma. However, a wealth of research supports the notion that BLV infection causes widespread abnormal immune function. BLV infection can impact cells of both the innate and adaptive immune system and alter proper functioning of uninfected cells. Despite strong evidence of abnormal immune signaling and functioning, little research has investigated the large-scale effects of BLV infection on host immunity and resistance to other infectious diseases. This review focuses on mechanisms of immune suppression associated with BLV infection, specifically aberrant signaling, proliferation and apoptosis, and the implications of switching from BLV latency to activation. In addition, this review will highlight underdeveloped areas of research relating to BLV infection and how it causes immune suppression.     

辣蓼黄酮对小鼠免疫功能调节作用的研究

为探讨辣蓼中黄酮类化合物对小鼠免疫功能的调节作用,试验用环磷酰胺(CTX)建立小鼠免疫抑制模型.以4种不同剂量(25、50、100和150mg/kg)的辣蓼黄酮正丁醇部分(n-butanol part of flavonoids,FNB)对小鼠灌胃给药,发现免疫抑制小鼠的脏器指数和血清中的细胞因子水平均有不同程度的升高...     

In vivo functions of the auxiliary genes and regulatory elements of feline immunodeficiency virus

Feline immunodeficiency virus (FIV) is a widespread lentivirus of domestic cats that causes an acquired immunodeficiency syndrome (AIDS)-like disease similar to human AIDS caused by human immunodeficiency virus. FIV has a complex genome structure including structural, enzymatic and auxiliary genes and regulatory elements. In this article, we review the in vivo roles of some of these FIV auxiliary genes and regulatory elements, especially focusing on the dUTPase, vif, and ORF-A genes and AP-1 binding site in the enhancer region of the long terminal repeat, by comparison with those of other non-primate lentiviruses. These genes and elements are considered to be important for viral replication, immunological response and pathogenesis in cats.     

Effects of age and immune suppression of sheep on fecundity, hatching and larval feeding of different strains of Haemonchus contortus

The effects of host age and immune suppression on abomasal parasitic infection in sheep were investigated following single experimental oral infections with MHco3 (ISE), MHco4 (WRS) and MHco10 (CAVR) strains of Haemonchus contortus in naïve 5-month-old crossbred lambs (n = 1 per group) and 15-month-old Greyface sheep treated with methyl prednisolone acetate (n = 2 per group) or without corticosteroid treatment (n = 2 per group). Adult female H. contortus in 5-month-old lambs (n = 1 per group) shed on average 6.5, 3.1 and 8.0 times more eggs than in 15-month-old sheep (n = 4 per group) following infection with MHco3 (ISE), MHco4 (WRS) and MHco10 (CAVR) strains of H. contortus, respectively, over a period of 28 days following the commencement of patency. There was no obvious effect of age of sheep or corticosteroid treatment on the abomasal establishment of H. contortus or on in vitro assays for egg hatching or larval feeding at different concentrations of anthelmintics, although statistical analysis could not be performed due to the small group sizes.     

相同免疫程序在猪伪狂犬病阳性场和阴性场免疫效果分析

为确定猪伪狂犬病常用免疫程序是否在阴性场和阳性场均适宜,分别于猪伪狂犬病阴性场和阳性场选取胎次、日龄、母源抗体水平相近的90头仔猪进行试验。两组采用相同的免疫程序,分别于仔猪2、4、6、8、11、13周龄采血检测PRV-gB/gE抗体。结果显示,伪狂犬病阴性场商品猪2、4、6、8周龄PRV-gB抗体阳性率分别为100%、90%、60%、40%,经过2次免疫,阴性场商品猪PRV-gB抗体阳性率上升至100%。伪狂犬病阳性场商品猪2、4、6、8、11、13周龄PRV-gE抗体阳性率分别为72.7%、73.3%、60%、60%、6%、0;PRV-gB抗体阳性率在2、4、6、8周龄均为100%,11周龄下降至60%,13周龄下降至13.3%,与PRV-gE抗体变化趋势一致。由此可知,猪伪狂犬病常用免疫程序在阴性场取得较好的免疫效果。     

Oral Recombinant Feline Interferon-Omega as an alternative immune modulation therapy in FIV positive cats: Clinical and laboratory evaluation

Recombinant-Feline Interferon-Omega (rFeIFN-ω) is an immune-modulator licensed for use subcutaneously in Feline Immunodeficiency virus (FIV) therapy. Despite oral protocols have been suggested, little is known about such use in FIV-infected cats. This study aimed to evaluate the clinical improvement, laboratory findings, concurrent viral excretion and acute phase proteins (APPs) in naturally FIV-infected cats under oral rFeIFN-ω therapy (0.1 MU/cat rFeIFN-ω PO, SID, 90 days). 11 FIV-positive cats were treated with oral rFeIFN-ω (PO Group). Results were compared to previous data from 7 FIV-positive cats treated with the subcutaneous licensed protocol (SC Group). Initial clinical scores were similar in both groups. Independently of the protocol, rFeIFN-ω induced a significant clinical improvement of treated cats. Concurrent viral excretion and APP’s variation were not significant in the PO Group. Oral rFeIFN-ω can be an effective alternative therapy for FIV-infected cats, being also an option for treatment follow-up in cats submitted to the licensed protocol.     

Diagnosing feline immunodeficiency virus (FIV) infection in FIV-vaccinated and FIV-unvaccinated cats using saliva

We recently showed that two immunochromatography point-of-care FIV antibody test kits (Witness FeLV/FIV and Anigen Rapid FIV/FeLV) were able to correctly assign FIV infection status, irrespective of FIV vaccination history, using whole blood as the diagnostic specimen. A third FIV antibody test kit, SNAP FIV/FeLV Combo (an enzyme-linked immunosorbent assay [ELISA]), was unable to differentiate antibodies produced in response to FIV vaccination from those incited by FIV infection. The aim of this study was to determine if saliva is a suitable diagnostic specimen using the same well characterized feline cohort. FIV infection status of these cats had been determined previously using a combination of serology, polymerase chain reaction (PCR) testing and virus isolation. This final assignment was then compared to results obtained using saliva as the diagnostic specimen utilizing the same three point-of-care FIV antibody test kits and commercially available PCR assay (FIV RealPCR). In a population of cats where one third (117/356; 33%) were FIV-vaccinated, both immunochromatography test kits accurately diagnosed FIV infection using saliva via a centrifugation method, irrespective of FIV vaccination history. For FIV diagnosis using saliva, the specificity of Anigen Rapid FIV/FeLV and Witness FeLV/FIV was 100%, while the sensitivity of these kits was 96% and 92% respectively. SNAP FIV/FeLV Combo had a specificity of 98% and sensitivity of 44%, while FIV RealPCR testing had a specificity of 100% and sensitivity of 72% using saliva. A revised direct method of saliva testing was trialed on a subset of FIV-infected cats (n = 14), resulting in 14, 7 and 0 FIV positive results using Anigen Rapid FIV/FeLV, Witness FeLV/FIV and SNAP FIV/FeLV Combo, respectively. These results demonstrate that saliva can be used to diagnose FIV infection, irrespective of FIV vaccination history, using either a centrifugation method (Anigen Rapid FIV/FeLV and Witness FeLV/FIV) or a direct method (Anigen Rapid FIV/FeLV). Collection of a saliva specimen therefore provides an acceptable alternative to venipuncture (i) in fractious cats where saliva may be easier to obtain than whole blood, (ii) in settings when a veterinarian or trained technician is unavailable to collect blood and (iii) in shelters where FIV testing is undertaken prior to adoption but additional blood testing is not required.     

多糖的免疫调节作用与研究进展

动植物中存在着广泛的免疫活性多糖。近年来多糖在促进和调节机体免疫功能方面已有较大的进展,本文主要就多糖对免疫器官、免疫细胞、免疫分子、免疫信息等方面的调节作用作一综述。     

Adaptive immunity to Anaplasma pathogens and immune dysregulation: implications for bacterial persistence

Anaplasma marginale is an obligate intraerythrocytic bacterium that infects ruminants, and notably causes severe economic losses in cattle worldwide. Anaplasma phagocytophilum infects neutrophils and causes disease in many mammals, including ruminants, dogs, cats, horses, and humans. Both bacteria cause persistent infection - infected cattle never clear A. marginale and A. phagocytophilum can also cause persistent infection in ruminants and other animals for several years. This review describes correlates of the protective immune response to these two pathogens as well as subversion and dysregulation of the immune response following infection that likely contribute to long-term persistence. I also compare the immune dysfunction observed with intraerythrocytic A. marginale to that observed in other models of chronic infection resulting in high antigen loads, including malaria, a disease caused by another intraerythrocytic pathogen.     

Cutaneous immune mechanisms in canine leishmaniosis due to Leishmania infantum

Canine leishmaniosis (CanL) caused by the parasite Leishmania infantum is a systemic disease with variable clinical signs. The disease is endemic in the Mediterranean countries and dogs are the main domestic reservoir of the parasite. The quite complicated immune response against the parasite is crucial for the evolution of CanL infection with the skin playing a major role in its immunopathogenesis.After the inoculation of Leishmania promastigotes into the dermis by sand fly bites, complement factors, Langerhan's cells, neutrophils, fibroblasts and keratinocytes are involved in the activation of the innate arm of the skin immune system, with the macrophages and dendritic cells to play a major key role.The effective activation of cellular immunity is the cornerstone of dog's resistance against the parasite. Promastigotes reaching the dermis are engulfed, processed and transferred by APCs to draining lymph nodes to stimulate naïve T-cells for proliferation and differentiation into armed effector T-cells. Th1 cells activate the infected macrophages to kill Leishmania, whereas Th2 cells divert the immune response to humoral immunity and down regulation of cellular immunity with Th1 cell anergy. Inhibition of co-stimulatory molecules expression by infected macrophages contributes to T-cell anergy. In canine subclinical infections cutaneous lymphocytic infiltrate and parasites are absent, as opposed to dogs with clinical leishmaniosis. CD8+ cells constitute a significant population of cellular immunity in CanL since they outnumber CD4+ cells in the dermis, producing IFN-γ in sub clinically infected dogs and high levels of IL-4 in dogs with clinical leishmaniosis.Numerous B-lymphocytes have been shown to heavily infiltrate the dermis at least in exfoliative dermatitis in CanL. A mixed Th1/Th2 cytokine profile has been found in the dermis of naturally infected with L. infantum dogs. In the skin of dogs with clinical leishmaniosis, where plasma cells outnumber T lymphocytes in the dermal infiltrate, there is an overproduction of IL-4, IL-13 and TNF-α leading to Th2-biased humoral immune response. The issue of humoral immunity polarization in CanL remains controversial. Much still needs to be learned about other mechanisms underlying the complex interaction between the skin immune system and the parasite.     

鱼类免疫系统的研究进展

免疫系统是指机体识别自身和非自身物质以抵御病害生物入侵和感染的一个防御系统,它的主要功能是防御和维护自身的稳定。鱼类的免疫系统主要包括：免疫组织和器官、细胞免疫、体液免疫因子三大类。本文就鱼类免疫系统的三个方面及与免疫系统有关的黏膜免疫、营养免疫等方面作一概述。     

Methods for diagnosis of canine leishmaniasis and immune response to infection

Canine leishmaniasis (CanL) caused by Leishmania infantum (syn. L. chagasi, in Latin America), which is transmitted by the bite of phlebotomine sand flies, is endemic and affects millions of dogs in Europe, Asia, North Africa and South America. It is an emergent disease in North America. Early detection and treatment of infected animals may be critical in controlling the spread of the disease and is an essential part of human zoonotic visceral leishmaniasis control. The laboratory diagnosis of CanL still poses a challenge, despite progress made in the development of several direct and indirect methods. An effective diagnosis test, apart of being able to confirm a clinical suspicion in a single patient as well as to detect infection in asymptomatic dogs, should have high sensitivity, specificity and reproducibility; it must be simple, easy to perform, non-expensive, feasible in regional laboratories or adaptable for field conditions. Ideally, it should detect all Leishmania-infected dogs, preferentially using non-invasive collection of biological samples. In this paper we review the advantages and shortcomings of the available procedures for CanL diagnosis in the different phases, e.g. pre-patent and patent period of the infection and methods to determine the related immune response.     

Cloning of feline FOXP3 and detection of expression in CD4+CD25+ regulatory T cells

Feline and primate immunodeficiency viruses (FIVs, SIVs, and HIV) are transmitted via direct contact (e.g. fighting, sexual contact, and mother–offspring transmission). This dynamic likely poses a behavioral barrier to cross-species transmission in the wild. Recently, several host intracellular anti-viral proteins that contribute to species-specificity of primate lentiviruses have been identified revealing adaptive mechanisms that further limit spread of lentiviruses between species. Consistent with these inter-species transmission barriers, phylogenetic evidence supports the prediction that FIV transmission is an exceedingly rare event between free-ranging cat species, though it has occurred occasionally in captive settings. Recently we documented that puma and bobcats in Southern California share an FIV strain, providing an opportunity to evaluate evolution of both viral strains and host intracellular restriction proteins. These studies are facilitated by the availability of the 2× cat genome sequence annotation. In addition, concurrent viral and host genetic analyses have been used to track patterns of migration of the host species and barriers to transmission of the virus within the African lion. These studies illustrate the utility of FIV as a model to discover the variables necessary for establishment and control of lentiviral infections in new species.     

Crossbreeding parameters of general immune response traits in White Leghorn chickens

Crossbreeding parameters of immune response traits were estimated from a set of well characterized crossbred populations derived from three chicken lines selected over 12 generations for three different general immune response traits and their F1, F2 and backcrosses. The three traits investigated were the selection criteria from each of the lines, i.e. antibody response to the Newcastle disease virus vaccine 3 weeks after vaccination (ND3), cell-mediated immune response (response to phytohemagglutinin, PHA) and phagocytic activity measured as carbon clearance (CC). Crossbreeding parameters included direct and maternal additive line effects, direct and maternal heterosis as well as direct epistatic recombination loss. They were estimated as linear combinations of genetic group effects estimated using animal model methodology. Significant line differences were obtained for ND3 and, to a lesser extent, CC. They were mainly due to direct effects, maternal effects being significant for none of the 3 traits. Significantly negative direct heterosis effects were also observed for ND3 and CC, but not for PHA. Maternal heterosis effects were not estimated for CC. They were non significant for PHA, and negative and significant (− 0.78 ± 0.24) for ND3. The significant favourable recombination gain estimated for ND3 (3.21 ± 0.88) indicates that epistatic interactions could be important for this trait.The present work shows that it was worthwhile to complete second generation crosses to be able to assess to what extent immunity gained by selection is maintained in advanced crossbred generations, and to compare the transmission of immune traits implicated in different aspects of immunity.     

2012～2013年辽宁省猪瘟免疫抗体监测分析

本研究采用抗体阻断ELISA方法对2012年和2013年辽宁省猪瘟免疫抗体进行跟踪监测,结果表明,2012年和2013年辽宁省猪瘟免疫抗体合格率均高于国家免疫方案的要求,并且2013年的免疫效果好于2012年。从检测结果分析,种猪场和商品猪场猪瘟的免疫情况明显好于散养猪的猪瘟免疫,因此建议采取有效措施加强散养猪的猪瘟免疫工作。     

Characterization of immune response in Staphylococcus aureus chronically infected bovine mammary glands during active involution

The aim of this study was to characterize the immune response in Staphylococcus aureus chronically infected bovine mammary glands during active involution. Twenty-one Holstein non-pregnant cows in late lactation either uninfected or with chronic naturally acquired S. aureus intramammary infections (IMI) were included in this study. Cows were slaughtered at 7, 14 and 21 d after cessation of milking and samples for immunohistochemical analysis were taken. Protein expression of toll-like receptor 2 (TLR2) and TLR4 was significantly higher in S. aureus-infected quarters than in uninfected controls at the three involution stages studied. Protein expression of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1α and IL-17 was significantly affected by IMI; being higher in S. aureus-infected than uninfected quarters during all evaluated stages. In S. aureus-infected and uninfected quarters protein expression of lactoferrin increased from day 7–14 of involution, decreasing significantly to day 21 in mammary quarters with chronic infections. The number of monocytes-macrophages was significantly higher in S. aureus-infected than in uninfected control quarters at 7 and 21 d of involution. The number of T lymphocytes was significantly higher in S. aureus-infected than in uninfected quarters at 7 and 14 d of involution while the number of B lymphocytes was significantly higher in S. aureus-infected than in uninfected quarters during all evaluated stages, showing a progressive increase as involution advanced. These results demonstrated a sustained and exacerbated innate and adaptive immune response during chronic S. aureus IMI, playing a critical role in the infection control during active involution.     

桑枝皮多糖对小鼠的免疫调节试验

多糖对生物体具有免疫调节作用,从桑枝皮中可以提取获得多糖物质。分别以300、600、900 mg/kg剂量的桑枝皮多糖给正常小鼠和免疫抑制小鼠灌胃,对照组给予等量的蒸馏水,每天给药1次,连续给药7 d后检测观察小鼠体内部分生理生化指标的变化,探究桑枝皮多糖对小鼠的免疫调节作用机制。结果显示:桑枝皮多糖可增强正常小鼠因2,4-二硝基氟苯(DNFB)引起的迟发性变态反应以及免疫器官的发育和脾脏淋巴细胞增殖能力,试验组小鼠的血清溶血素抗体积数、碳廓清能力、NK细胞活性、白介素-2(IL-2)的浓度均显著高于对照组(P<0.05);桑枝皮多糖对免疫抑制试验小鼠的免疫功能也有一定的提升作用,除巨噬细胞吞食能力外,其他检测指标均有显著改善。试验结果还表明桑枝皮多糖改善小鼠免疫功能的生理生化指标,具有一定的量效关系。     

口服PHA复合物对犬细小病毒疫苗免疫效果的影响

为了更好地指导犬细小病毒病的防治,减少犬患细小病毒病的几率,本文通过试验验证了PHA（植物血凝素）复合物是否对犬细小病毒疫苗有增效作用。结果表明,PHA复合物与英特威二联苗联用可提高犬对英特威二联苗的抗体应答能力,可以更好地防治犬细小病毒病。