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。     

牛传染性鼻气管炎基因工程疫苗研究进展

牛传染性鼻气管炎是由牛疱疹病毒1型感染而引起的高传染性疾病。该病临床症状以呼吸道炎症为主,另外伴有结膜炎、流产、脑炎等并发症。20世纪50年代早期,美国科罗拉多州某些牧场首次发现该病。目前缺乏有效的治疗性药物,对动物实施疫苗免疫是防控该病较理想的方法。目前,某些国家仍然使用传统疫苗,然而,经过基因改造的糖蛋白E基因缺失疫苗已在欧盟上市,该疫苗分为活苗和灭活苗两种。文章着重对牛传染性鼻气管炎基因缺失疫苗、亚单位疫苗、活载体疫苗及DNA疫苗最新的研究进行评述。     

Bovine herpes virus-1 (BoHV-1) in cattle–a review with emphasis on reproductive impacts and the emergence of infection in Ireland and the United Kingdom

Bovine reproductive disease attributable to bovine herpes virus-1 (BoHV-1) was first described in Germany in the 19^th century, being recognised primarily as the cause of infectious vulvovaginitis and balanoposthitis until the mid-1950s when a more virulent strain of the virus (BoHV-1.1) associated with respiratory disease (infectious bovine rhinotracheitis; IBR) emerged in the western United States. Subsequently, IBR emerged as a clinical condition in Europe, from the 1970s onward. While the ability of BoHV-1 to produce respiratory disease is now well recognised, the potential negative outcomes of infection on fertility and reproduction are less frequently considered. This review was conducted against the background of the prioritization of disease caused by BoHV-1 as one of several diseases to be addressed by Animal Health Ireland, with the twin goals of summarizing the published literature on the potential outcomes of infection at different stages of breeding and pregnancy, and of describing the emergence of BoHV-1 as a significant pathogen in Ireland and the UK.     

A specific PCR to differentiate between gE negative vaccine and wildtype bovine herpesvirus type 1 strains

In the context of infectious bovine rhinotracheitis (IBR) control programmes using glycoprotein E (gE) deleted marker vaccines, a PCR assay was developed to allow the genotypic differentiation between wildtype bovine herpesvirus type 1 (BoHV-1) and gE negative strains. This assay is based on the PCR amplification of a 281 bp DNA fragment within the gE gene. The specificity of the amplification was confirmed by restriction endonuclease analysis and nucleotide sequencing of the PCR product. Its ability to determine the gE genotype of BoHV-1 strains was demonstrated on isolates coming from 20 experimental calves infected with four different BoHV-1 strains. This PCR assay may be a useful tool for monitoring the spread of live marker vaccine and the gE genotype of viral field isolates.     

Infectious bovine rhinotracheitis (IBR) in the canton of Jura: an epidemiological outbreak investigation

Following an abortion in a beef herd in the summer of 2009, three outbreaks of infectious bovine rhinotracheitis (IBR) were diagnosed in the cantons of Jura and Neuchatel. An epidemiological outbreak investigation was conducted with the aims to identify the source of introduction of the bovine herpes virus 1 (BoHV-1) into the affected herds and to prevent further spread of the disease. The attack rates in the three outbreak farms were 0.89, 0.28 and 0, respectively. BoHV-1 could be isolated from nasal swabs of two animals originating from one of the affected farms. Comparative restriction enzyme analysis revealed slight differences between the isolates of the two animals, but a high similarity to previous BoHV-1 isolates from the canton of Jura, as well as to a French BoHV-1 isolate. This IBR outbreak has shown the importance of reporting and analyzing abortions. The current disease outbreaks recall the main risk factors for the spread of IBR in Switzerland: purchase and movement of bovines and semen of often unknown IBR status.     

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 rhino-tracheitis 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...     

Recent developments in fish vaccinology

During the last 10 to 20 years vaccination has become established as an important method for prevention of infectious diseases in farmed fish, mainly salmonid species. So far, most commercial vaccines have been inactivated vaccines administered by injection or immersion. Bacterial infections caused by Gram-negative bacteria such as Vibrio sp., Aeromonas sp., and Yersinia sp. have been effectively controlled by vaccination. With furunculosis, the success is attributed to the use of injectable vaccines containing adjuvants. Vaccines against virus infections, including infectious pancreatic necrosis, have also been used in commercial fish farming. Vaccines against several other bacterial and viral infections have been studied and found to be technically feasible. Pasteurellosis, streptococcosis (lactococcosis) and infections with iridoviruses are candidate diseases for control by immunoprophylaxis in the near future. The overall positive effect of vaccination in farmed fish is reduced mortality. However, for the future of the fish farming industry it is also important that vaccination contributes to a sustainable biological production with negligible consumption of antibiotics. A potential side-effect associated with injectable vaccines is local reactions in the peritoneal cavity. The paper presents recent developments in immunoprophylaxis of fish and some problems that should be addressed by the research community in the years to come.     

Comparison of the immunizing effectiveness of subunit vaccine and inactivated viral oil vaccine against infectious rhinotracheitis of cattle

Trials were conducted on rabbits and cattle to compare the immunizing effectiveness of the subunit vaccine against infectious bovine rhinotracheitis (IBR), representing antigens separated by the solubilization of the IBR virus-infected cells by means of Triton X-100 with oil adjuvant, with the inactivated oil IBR vaccine. The rabbits inoculated and re-vaccinated with both vaccines in an interval of three weeks produced neutralizing antibodies in medium titres, the values of these antibodies were balanced in both groups. Cattle immunized with the subunit vaccine reacted to the inoculation and re-vaccination by producing serum antibodies of higher titres, as compared with the cattle inoculated with the virus vaccine; secretory antibodies were detected only after re-vaccination and had balanced values in both test groups. After intranasal infection with the virulent virus performed after 14 days from re-vaccination, the calves inoculated with the subunit and virus vaccines were protected against clinical disease whereas the non-inoculated control calves fell ill with symptoms characteristic of IBR. The immunized animals of both experimental groups had a smaller amount of virus p.i. in nasal secretions and for a shorter time than the control non-inoculated calves. The intensity of multiplication and persistence of infectious virus excretion were the same in both experimental groups.     

Distribution of latent bovine herpesvirus 2 DNA in tissues of experimentally infected sheep

The biology of latent infection by bovine herpesvirus 2 (BoHV-2), the agent of mammillitis in cows, remains largely unknown. We herein report attempts to reactivate the latent infection and investigated the sites of BoHV-2 latency in experimentally infected sheep. Ewes inoculated with BoHV-2 in the udder’s skin shed virus for up to five days, developed mammillitis and seroconverted. However, attempts to reactivate latent infection by dexamethasone administration at day 40 pi failed. Nevertheless, viral DNA - and not infectious virus - was detected by PCR in several nerve ganglia and/or regional lymph nodes (LNs) of all animals at day 40 post-reactivation. Likewise, lambs previously inoculated with BoHV-2 in the nose harbored latent viral DNA in trigeminal ganglia, tonsils and regional LNs. These results demonstrate that BoHV-2 establishes latent infection in nerve ganglia and in regional lymphoid tissues, yet virus reactivation is not easily achieved by standard protocols used.     

鸡传染性法氏囊病新型疫苗的研究进展

鸡传染性法氏囊病(IBD)是由鸡传染性法氏囊病病毒(IBDV)引起的雏鸡的一种高度接触性传染病,自1962年报道以来,世界上主要养禽国家和地区均有流行,给养禽业带来严重经济损失。目前,IBD防控的主要方法是采用疫苗接种,使易感雏鸡获得主动或被动免疫保护,因此疫苗的质量对临床上IBD的防控起着至关重要的作用。虽然各国均有较好的商品化疫苗,但随着IBDV毒株的不断变异,商品化疫苗的抗原性与流行毒株不能完全匹配,临床上免疫失败时有发生,因此迫切需要研发与临床流行毒株相匹配的新型疫苗用于IBD的防控。对近期IBD的基因缺失苗、亚单位疫苗、DNA疫苗以及活载体疫苗等新型疫苗的研究进展进行概述,以此为IBD新型疫苗的研究提供参考。     

Prevalence of antibodies to infectious bovine rhinotracheitis, parainfluenza 3, bovine respiratory syncytial, and bovine viral diarrhea viruses in cattle in Saskatchewan and Alberta

A total of 1745 healthy cattle from 295 farms in Saskatchewan and Alberta was tested by ELISA for antibodies to four viruses. Antibodies to infectious bovine rhinotracheitis (IBR) virus were found in 37.8% of sera (59.5% of properties), to parainfluenza 3 (PI3) virus in 93.9% of sera (99.7% of properties), to bovine respiratory syncytial (BRS) virus in 78.5% of sera (86.6% of properties), and to bovine viral diarrhea (BVD) virus in 40.6% of sera (66.7% of properties)

The prevalence of PI3 viral antibodies among Saskatchewan cattle was not affected by district of origin, breed, sex, age, or vaccination practices, though BRS viral antibodies appeared less frequent in young, male, and unvaccinated animals. Antibodies to IBR and BVD viruses were less prevalent in the Prince Albert/Tisdale districts and in young, male, and unvaccinated animals, but were more common in Holstein cattle. Antibodies to IBR virus appeared less frequent in Herefords. Antibodies were more prevalent in cattle which had been vaccinated against IBR, BRS, and BVD virus infections.

The relatively small number of cattle sampled from Alberta had a similar prevalence of antibodies to PI3 and BRS viruses to that seen in cattle in Saskatchewan, though IBR and BVD prevalence rates were lower.

     

Molecular characterisation of a field strain of bubaline herpesvirus isolated from buffaloes (Bubalus bubalis) after pharmacological reactivation

Two healthy buffaloes (Bubalus bubalis) in a herd which had not been vaccinated against infectious bovine rhinotracheitis (IBR), were selected for their seropositivity for anti-bovine herpesvirus type 1 (BoHV-1) glycoprotein E antibodies, and injected intramuscularly daily with dexamethasone for five consecutive days (day 1 to day 5) to reactivate any latent herpesvirus. Blood samples and nasal and vaginal swabs were collected daily from day 5 to day 15 from each buffalo for virological examination. All the vaginal swabs and blood samples were negative, but 13 of the 22 nasal swabs were positive; a cytopathic effect was observed in primary cultures of bovine fetal lung cells, and the viral isolates were identified as a herpesvirus by PCR. The viral strains were characterised by the sequence analysis of the genes coding for glycoproteins D and B, and the gene sequences were then used for phylogenetic analysis. The isolates from both buffaloes appeared identical at the level of the two genes, and were more closely related to bovine herpesvirus type 5 than to BoHV-1.     

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.     

Bovine herpesvirus 4 immediate early 2 (Rta) gene is an essential gene and is duplicated in bovine herpesvirus 4 isolate U

The ORF50/Rta gene has been shown to be an essential gene for many gammaherpesviruses. Although the BoHV-4 ORF50/Rta homolog, immediate early gene 2 (IE2), has been shown to activate several BoHV-4 early and late promoters in cotransfection assays, there is no direct proof of its indispensability for progression of the virus to the lytic replication cycle in the context of the viral genome. In the present communication, replication defective BoHV-4-V.test IE2 mutants were efficiently rescued, with respect to production of infectious virus and DNA replication, upon the expression of BoHV-4 ORF50/Rta in trans. Surprisingly, in the course of our studies, we discovered that the IE2 gene is duplicated in the genome of BoHV-4-U.     

Efficacy of an inactivated,recombinant bovine herpesvirus type 5 (BoHV-5) vaccine

Bovine herpesvirus type 5 (BoHV-5) is the causative agent of bovine herpetic encephalitis. In countries where BoHV-5 is prevalent, attempts to vaccinate cattle to prevent clinical signs from BoHV-5-induced disease have relied essentially on vaccination with BoHV-1 vaccines. However, such practice has been shown not to confer full protection to BoHV-5 challenge. In the present study, an inactivated, oil adjuvanted vaccine prepared with a recombinant BoHV-5 from which the genes coding for glycoprotein I (gI), glycoprotein E (gE) and membrane protein US9 were deleted (BoHV-5 gI/gE/US9⁻), was evaluated in cattle in a vaccination/challenge experiment. The vaccine was prepared from a virus suspension containing a pre-inactivation antigenic mass equivalent to 10^7.69 TCID₅₀/dose. Three mL of the inactivated vaccine were administered subcutaneously to eight calves serologically negative for BoHV-5 (vaccinated group). Four other calves were mock-vaccinated with an equivalent preparation without viral antigens (control group). Both groups were boostered 28 days later. Neither clinical signs of disease nor adverse effects were observed during or after vaccination. A specific serological response, revealed by the development of neutralizing antibodies, was detected in all vaccinated animals after the first dose of vaccine, whereas control animals remained seronegative. Calves were subsequently challenged on day 77 post-vaccination (pv) with 10^9.25 TCID₅₀ of the wild-type BoHV-5 (parental strain EVI 88/95). After challenge, vaccinated cattle displayed mild signs of respiratory disease, whereas the control group developed respiratory disease and severe encephalitis, which led to culling of 2/4 calves. Searches for viral DNA in the central nervous system (CNS) of vaccinated calves indicated that wild-type BoHV-5 did not replicate, whereas in CNS tissues of calves on the control group, viral DNA was widely distributed. BoHV-5 shedding in nasal secretions was significantly lower in vaccinated calves than in the control group on days 2, 3, 4 and 6 post-challenge (pc). In addition, the duration of virus shedding was significantly shorter in the vaccinated (7 days) than in controls (12 days). Attempts to reactivate latent infection by administration of dexamethasone at 147 days pv led to recrudescence of mild signs of respiratory disease in both vaccinated and control groups. Infectious virus shedding in nasal secretions was detected at reactivation and was significantly lower in vaccinated cattle than in controls on days 11–13 post-reactivation (pr). It is concluded that the inactivated vaccine prepared with the BoHV-5 gI/gE/US9⁻ recombinant was capable of conferring protection to encephalitis when vaccinated cattle were challenged with a large infectious dose of the parental wild type BoHV-5. However, it did not avoid the establishment of latency nor impeded dexamethasone-induced reactivation of the virus, despite a significant reduction in virus shedding after challenge and at reactivation on vaccinated calves.     

Pestivirus and alphaherpesvirus infections in Swedish reindeer (Rangifer tarandus tarandus L.)

Herding semi-domesticated reindeer has economic and social value for Sami people in the northern territories of Fennoscandia. However, with the intensification of reindeer husbandry, interspecies transmission of pathogens between reindeer and domestic animals may become a problem, especially for countries such as Sweden, Norway, and Finland where pestivirus and alphaherpesvirus have been eradicated in domestic ruminants. This study, which included 1158 Swedish reindeer, showed relatively high prevalence of antibodies against bovine viral diarrhoea virus (BVDV) (32%) and bovine herpesvirus-1 (BoHV-1) (53%). Adult animals were more often seropositive for BVDV and BoHV-1 (50% and 78%, respectively) than were calves (18 and 11%, respectively). While the seroprevalence of alphaherpesvirus was similar in different herding districts, pestivirus seropositivity was highest in the South and diminished towards the North of the Swedish reindeer herding area. High correlation of the seropositivity against both pathogens at both individual and herd levels may indicate possible mutual synergetic effects and may be explained by the immunosuppressive nature of the viruses. While alphaherpesvirus seroprevalence was probably related to putative cervid herpesvirus 2 (CvHV-2), the pestivirus infecting reindeer remains undefined. The virus neutralisation test of reindeer sera using different pestivirus strains, revealed higher titres against Border disease virus strains like 137/4 (BDV-1) and Reindeer-1 (BDV-2) than against BVDV-1. However, the virus was not identified by real time RT-PCR in any of the samples (n=276) from seronegative reindeers. The study showed that pestivirus and alphaherpesvirus infections are endemic in the Swedish reindeer population.     

Viral aetiologies for bovine respiratory disease

Extract

Bovine respiratory disease (BRD) is a major health problem of cattle all over the world. Financial losses arise from the loss in production, cost of treatment and mortality. Incidence varies with seasons, the highest occurring in autumn and winter. Virus infections such as infectious bovine rhinotracheitis (IBR), parainfluenza 3 (P13) and bovine respiratory syncytial (BRS) viruses have all been incriminated as causes for BRD. It has been suggested that bovine viral diarrhoea (BVD) virus may also contribute to BRD because of its immunosuppressive effects, thus increasing the susceptibility of the host to other respiratory pathogens.     

Seroepidemiological study of bovine respiratory viruses (BRSV, BoHV-1, PI-3V, BVDV, and BAV-3) in dairy cattle in central region of Iran (Esfahan province)

Respiratory diseases in calves are responsible for major economic losses in both beef and dairy production. Several viruses, such as bovine respiratory syncytial virus (BRSV), bovine herpes virus-1 (BoHV-1), bovine parainfluenza virus-3 (BPI-3V), bovine viral diarrhea virus (BVDV), and bovine adenoviruses (BAV), are detected in most clinical cases with respiratory signs. The aim of this study is to define seroprevalences of five major viral causes of bovine respiratory infections in cattle in central region of Iran (Esfahan province). The population targeted was 642 dairy cows (Holstein–Friesian) from 25 farms. Samples of blood serum from female cattle were examined. Sera were tested by commercial ELISA kits to detect antibody against BRSV, BoHV-1, BPI-3V, BVDV, and BAV-3. The results were analyzed by Chi-square test. In the present study, seroprevalences of BRSV, BoHV-1, PI3V, BVDV, and BAV-3 were 51.1%, 72%, 84.4%, 49.2%, and 55.6%, respectively. The present study shows that infections of bovine respiratory viruses are very common in cattle in Esfahan.