牛传染性鼻气管炎病毒基因工程疫苗研究进展

牛传染性鼻气管炎病毒属于疱疹病毒I型,可导致牛发生高度接触性、病毒性传染病,病牛和带毒牛是主要传染源,感染牛出现结膜炎、脑炎和流产等临床症状,危害较大。牛传染性鼻气管炎病毒具有潜伏感染特征,可以潜伏在三叉神经节等部位,在机体抵抗力下降时就会发病,潜伏感染的牛可以长期带毒并不断向外界排毒。控制该病主要通过疫苗免疫,当前牛传染性鼻气管炎疫苗主要包括传统的灭活苗、弱毒苗以及基因工程疫苗,其中基因工程疫苗是一种新型疫苗,包括基因缺失疫苗、活载体疫苗、亚单位疫苗及DNA疫苗,各种疫苗各有优点。本文主要综述牛传染性鼻气管炎基因工程疫苗的最新研究进展,为该病的综合防控奠定基础,供参考。     

牛传染性鼻气管炎疫苗的研究进展

牛传染性鼻气管炎(infectious bovine rhinotracheitis,IBR)是由牛传染性鼻气管炎病毒(infectious bovine rhinotracheitis virus,IBRV)即牛疱疹病毒1型(BoHV-1)感染所引起的一种高度接触性传染病。该病给我国养牛业带来了巨大的经济损失。由于缺乏有效的治疗性药物,疫苗免疫仍然是防控该病的有效措施。当前,牛传染性鼻气管炎疫苗主要包括灭活疫苗、弱毒疫苗2种常规疫苗和亚单位疫苗、DNA疫苗、IBRV基因缺失疫苗、病毒活载体疫苗4种基因工程疫苗,各种疫苗各有优点。现对上述疫苗的最新研究进展进行综述,以期为IBRV疫苗的研究与开发提供参考。     

牛传染性鼻气管炎疫苗研究进展

牛传染性鼻气管炎(IBR)是由牛传染性鼻气管炎病毒(IBRV)感染家养牛引起的一种热性接触性传染病。由于缺乏有效的治疗性药物,因此疫苗免疫仍然是防控该病的关键措施。针对该病常用的疫苗主要有灭活疫苗和活疫苗,而基因缺失活疫苗由于具有免疫标识,已成为新型疫苗研发的主流方向。一些发达国家已利用基因缺失标记疫苗,如IBRV gE缺失疫苗,进行免疫根除计划并净化了该病。然而,由于现存的疫苗仍存在免疫抑制与潜伏感染等问题,亟需研制更有效的标记疫苗。论文就牛传染性鼻气管炎病毒的病原学特征、免疫抑制及疫苗研发进展进行综述,以期为IBR有效疫苗的研发及其在防控上的应用提供参考。     

牛传染性鼻气管炎诊断方法研究进展

牛传染性鼻气管炎(IBR)是由牛传染性鼻气管炎病毒(IBRV),即牛疱疹病毒1型(BoHV-1)所引起的以上呼吸道炎症为主的一种牛的急性、热性、接触性传染病,呈世界性流行。IBR的早期准确诊断,对该病的防控具有不可忽视的作用。目前,IBR的诊断方法主要包括病原学诊断和血清学诊断方法。病原学诊断具有特异和敏感及准确等特点,而血清学诊断具有敏感、快速、方便和价廉等特点。为了实施IBR的净化和根除计划,部分国家和地区已逐渐采用IBR基因缺失疫苗,配套使用鉴别诊断方法来鉴别IBR疫苗免疫和自然感染。论文就牛传染性鼻气管炎常用诊断方法的研究进展进行综述,以期为IBR的诊断和防控提供参考。     

三种疱疹病毒基因缺失疫苗的研究进展

当前伪狂犬病、牛传染性鼻气管炎等疱疹病毒基因缺失疫苗得以成功开发和广泛应用,鸡传染性喉气管炎病毒基因缺失疫苗的研究也取得一定的进展。基因缺失疫苗较灭活疫苗、弱毒疫苗在安全性、免疫原性、鉴别诊断等方面都具有明显的优势。基因缺失疫苗的开发和应用将为有效防控和彻底根除这些动物疫病带来了希望。     

鸡传染性喉气管炎基因工程疫苗的研究与应用

论述了鸡传染性喉气管炎亚单位疫苗、基因缺失疫苗、重组病毒活载体疫苗、基因疫苗的研究和应用进展情况,表明应用基因工程疫苗免疫可以从根本上改变鸡传染性喉气管炎的防治现状,使传染性喉气管炎的根除成为可能。     

牛传染性鼻气管炎病毒(gN-TK-gG-)三基因缺失突变株的构建

牛传染性鼻气管炎是由牛疱疹病毒Ⅰ型(BoHV-1)引起的一种牛的传染病,可导致严重的经济损失。疫苗接种是用于防控该病的重要手段,但现有疫苗在多个方面都有改进的余地。本试验利用pBoHV-1BAC载体和4次Red E/T重组,依次构建了BoHV-1gN~-(CT~-)、BoHV-1gN~-(CT~-30-32-)、BoHV-1gN~-TK-和BoHV-1gN~-TKgG-基因缺失突变株,其中gN缺失了胞外区30~32位氨基酸、胞质尾区CT端,TK基因缺失了1 079bp,gG基因缺失了1 335bp。pBoHV-1gN~-TK-gG-经磷酸钙法转染MDBK细胞后,出现细胞病变,成功拯救出三基因缺失病毒株BoHV-1gN~-TK-gG-。研究结果为牛传染性鼻气管炎新型基因缺失标记疫苗的开发奠定了基础。     

牛传染性鼻气管炎概述

牛传染性鼻气管炎(IBR)是由牛疱疹病毒I型(BoHV-I)引起的一种急性接触性疾病。主要从临床症状、流行病学特点、疫病动态、病原学、分子生物学、诊断和防控措施等方面来论述牛传染性鼻气管炎,以期为该病诊断、防控、疫苗研究提供参考。     

牛传染性鼻气管炎诊断方法的研究进展

牛传染性鼻气管炎是由牛传染性鼻气管炎病毒引起的一种牛的热性、急性、接触性传染病。该病是世界动物卫生组织(OIE)规定的必须上报的疾病之一,在我国也被列为二类疫病。牛传染性鼻气管炎可降低牛的肥育率、繁殖率和产奶量,给养牛业造成了重大经济损失。从病毒的分离鉴定、血清学以及分子生物学等方面对该病的诊断方法进行综述,以期为牛传染性鼻气管炎的检测和防控提供参考。     

牛传染性鼻气管炎诊断方法研究进展

牛传染性鼻气管炎是由牛传染性鼻气管炎病毒引起的一种牛的热性、急性、接触性传染病。该病是世界动物卫生组织(OIE)规定的必须上报的疾病之一,在我国也被列为二类疫病。牛传染性鼻气管炎可降低牛的肥育率、繁殖率和产奶量,给养牛业造成了重大经济损失。从病毒的分离鉴定、血清学以及分子生物学等方面对该病的诊断方法进行综述,以期为牛传染性鼻气管炎的检测和防控提供参考。     

Maternal immunity to infectious bovine rhinotracheitis and bovine viral diarrhea viruses: duration and effect on vaccination in young calves.

The immune response to modified live-virus bovine viral diarrhea (BVD) vaccine and infectious bovine rhinotracheitis (IBR) vaccine was examined in calves that had received passive maternal antibodies to these viruses. Blood serum samples from vaccinated and control (nonvaccinated) calves were examined for more than 1 year to determine the rate of decline of passive anti-BVD and anti-IBR antibodies and the effect that vaccination had on these antibody titers. The control calves lost their antibodies to BVD and IBR viruses at the rate of one half their remaining antibody titer every 21 days. Calves serologically responded to BVD vaccine at a time when maternal antibody titers remained between 1:96 and 1:20. However, animals did not seroconvert to the IBR vaccine until maternal antibodies had decreased and become undetectable. Evidence is presented to show that although passive immunity will inhibit IBR vaccination, priming for a secondary response will occur so that on subsequent vaccination, at a time when maternal antibodies have disappeared, the animals will respond anamnestically to IBR vaccination.     

A Controlled Field Study Using Live Virus Vaccines and an Antiserum in a Preconditioning Program

Thirty-five vaccinates and 29 control beef calves from five farms were studied. Vaccinates in group 1 received a modified live virus vaccine against infectious bovine rhinotracheitis (IBR) and bovine virus diarrhea (BVD) 30 days after shipment; vaccinates in groups 2, 3 and 4 received live virus vaccines agains IBR and bovine parainfluenza 3 (PI3) seven to 17 days before shipment. Half of group 5 were given bovine origin antiserum containing antibodies against IBR, BVD and PI3. Three weeks later, the animals that had received serum were given a live modified vaccine containing IBR, BVD and PI3. In group 1, WBC counts were lower in the vaccinates than in the controls for two weeks after vaccination. WBC counts in groups 3 and 4 were higher in vaccinates than in controls after addition to the feedlot. Seroconversions to BVD virus occured in all groups. Clinical disease apparently due to BVD affected one vaccinated calf in group 2 and eight calves in group 5. Combined weight gains were significantly higher in three groups of calves vaccinated before shipment compared to unvaccinated control animals after addition to the feedlot. Vaccination with IBR and PI3 live virus vaccines should be given at least 17 days before shipment to feedlots containing infected cattle. Antiserum containing antibodies against the three viruses showed no apparent advantage in preventing clinical respiratory disease over control calves not receiving the serum.     

Experimental Infection of Calves with Bovine Viral Diarrhoea Virus Type-2 (BVDV-2) Isolated from a Contaminated Vaccine

A non-cytopathic strain of BVDV-2 was isolated from a batch of live infectious bovine rhinotracheitis (IBR) vaccine, and inoculated intranasally into four 3-month-old calves. Severe signs of disease developed by days 4 and 6 in three of the calves, free of BVDV and antibodies to BVDV, that had been exposed to the virus. These calves survived the acute phase of the infection and progressively recovered. BVDV was consistently isolated, or the respective viral RNA was detected, in the buffy coats from blood samples collected starting from days 2 or 4 up to days 11 or 14 after the experimental infection. Viral RNA was also detected in sera from these infected calves until the presence in the serum of virus neutralizing antibodies was demonstrated. By contrast, the only calf having pre-existing neutralizing antibodies to BVDV at the start of the study was protected from the disease. No virus was detected at any time after experimental inoculation of this calf. Genomic characterization of the BVDV-2 isolated in cell cultures, or detected in sera from the experimentally infected animals, revealed 100% homology in the nucleotide sequence with the BVDV-2 detected as a contaminant of the live IBR virus vaccine. These findings provided evidence of the infective nature of the contaminant BVDV-2 and of its potential to generate disease outbreaks when inoculated into susceptible animals.     

Active and Passive Immunity to Bovine Viral Respiratory Diseases in Beef Calves After Shipment

Fifteen steers were vaccinated after shipment with a modified live virus vaccine containing infectious bovine rhinotracheitis (IBR), bovine virus diarrhea (BVD), and bovine myxovirus parainfluenza-3 (PI3), and 16 unvaccinated steers were kept as controls. Geometric mean titers one month after vaccination were highest to BVD, followed by PI3 and IBR. Weight gains were higher during 30 days after vaccination in the controls. One case of acute respiratory disease developed in one vaccinated calf. Revaccination 79 days after the first dose increased antibody to PI3 and BVD virus but not IBR. In a second trial, no clinical respiratory disease developed after shipment of 13 heifers that received an antibacterial-antiviral antiserum or in the 12 controls. Weight gains 30 days after shipment were identical in both groups.     

Identification of a mutant bovine herpesvirus-1 (BHV-1) in post-arrival outbreaks of IBR in feedlot calves and protection with conventional vaccination.

Outbreaks of infectious bovine rhinotracheitis (IBR) have recently been observed in vaccinated feedlot calves in Alberta a few months post-arrival. To investigate the cause of these outbreaks, lung and tracheal tissues were collected from calves that died of IBR during a post-arrival outbreak of disease. Bovine herpesvirus-1 (BHV-1), the causative agent of IBR, was isolated from 6 out of 15 tissues. Of these 6 isolates, 5 failed to react with a monoclonal antibody specific for one of the epitopes on glycoprotein D, one of the most important antigens of BHV-1. The ability of one of these mutant BHV-1 isolates to cause disease in calves vaccinated with a modified-live IBR vaccine was assessed in an experimental challenge study. After one vaccination, the majority of the calves developed humoral and cellular immune responses. Secondary vaccination resulted in a substantially enhanced level of immunity in all animals. Three months after the second vaccination, calves were either challenged with one of the mutant isolates or with a conventional challenge strain of BHV-1. Regardless of the type of virus used for challenge, vaccinated calves experienced significantly (P < 0.05) less weight loss and temperature rises, had lower nasal scores, and shed less virus than non-vaccinated animals. The only statistically significant (P < 0.05) difference between the 2 challenge viruses was the amount of virus shed, which was higher in non-vaccinated calves challenged with the mutant virus than in those challenged with the conventional virus. These data show that calves vaccinated with a modified-live IBR vaccine are protected from challenge with either the mutant or the conventional virus.     

Analysis of symptoms associated with bovine herpesvirus 1 vaccination

Between 1 May 1998 and 22 February 1999, it was compulsory for Dutch cattle farmers to take measures against bovine herpesvirus 1 (BHV1). Cattle on farms that were not certified as infectious bovine rhinotracheitis (IBR)-free had to be vaccinated twice a year. During the vaccination programme, both farmers and veterinarians reported side-effects of the vaccine. These reports were collected by the Stichting IBR/BVD Schade (SIS; Foundation for IBR/BVD Damage) in order to draw up a damage report. In 1999 in total 6977 cattle farmers lodged complaints which they considered to be related to the vaccination against BHV1. On these farms, 15,150 herd vaccinations had been performed, 10,269 of which were associated with one or more symptoms. During the compulsory vaccination period, 13% of the herd vaccinations led to symptoms and complaints. In March 1999, a number of vaccine batches were found to be contaminated with bovine virus diarrhoea (BVD) virus. For the purposes of this analysis, a 'known contaminated' herd vaccination was defined as one in which at least one 'known contaminated' batch or lot of vaccine was used. In total, 987 of 1007 herds vaccinated with 'known contaminated' vaccines developed one or more symptoms compatible with acute BVD. There were no commonly seen combinations of symptoms. For this reason, and because the start and end dates were not reported for 55% of the symptoms, it was not possible to detect a symptom pattern. Therefore there were no 'suspect' batches of vaccine which, although not contaminated with BVD virus, gave rise to symptoms. The number of BVD symptoms was determined for those herds with vaccination-related symptoms. There was no difference in the distribution frequency between batch numbers or between 'known contaminated' batches and 'non-suspect' batches. The farmers' definition of chronic wasting was used in this investigation, with the inevitable large differences in definition. The symptom chronic 'wasting' was reported for 3209 of the 10,269 herds with vaccination-related symptoms. On 161 farms (164 herd vaccinations) 'chronic wasting' accounted for more than 20% of the symptoms. As expected, other symptoms were reported in addition to wasting. The symptom 'chronic wasting' was reported more often on forms where a 'known contaminated' vaccine was used. Inactivated vaccine was used for 154 herd vaccinations. In 34 cases, one or more symptoms of acute BVD were reported. The frequency was the same as that for live vaccines. The frequency of reported symptoms tended to be lower with the inactivated vaccine. On the basis of the SIS data, no relationship was found between vaccine batch and reported symptoms. This may be because (i) the classification of a vaccine as 'known contaminated', 'non-suspect', and 'not known' may not have been in keeping with the real status of the vaccine, (ii) farmers may have reported symptoms selectively, and (iii) there is no relationship with vaccination against BHV1.     

Evidence for an immunocompromising effect of bovine pestivirus on bovid herpesvirus 1 vaccination

Five calves were given live intranasal vaccine against bovid herpesvirus 1 (BHV1) two days after intranasal inoculation of bovine pestivirus (BVDV). Another 5 were vaccinated in the absence of BVDV. Control unvaccinated groups were also maintained. All calves were challenged with virulent BHV1. The unvaccinated calves developed signs of infectious bovine rhinotracheitis (IBR) and both vaccinated groups showed a similar degree of clinical protection from IBR. Those given BVDV before vaccination shed up to 140 times more BHV1 (P less than 0.01) in the nasal mucus following challenge than those which had received BHV1 vaccine alone. The epidemiological significance of this is discussed.     

Evidence for an immunocompromising effect of bovine pestivirus on bovid herpesvirus 1 vaccination

Five calves were given live intranasal vaccine against bovid herpesvirus 1 (BHV1) two days after intranasal inoculation of bovine pestivirus (BVDV). Another 5 were vaccinated in the absence of BVDV. Control unvaccinated groups were also maintained. All calves were challenged with virulent BHV1. The unvaccinated calves developed signs of infectious bovine rhinotracheitis (IBR) and both vaccinated groups showed a similar degree of clinical protection from IBR. Those given BVDV before vaccination shed up to 140 times more BHV1 (P<0.01) in the nasal mucus following challenge than those which had received BHV1 vaccine alone. The epidemiological significance of this is discussed.