Effect of vaccination with recombinant canine distemper virus vaccine immediately before exposure under shelter-like conditions

Vaccination with modified-live virus (MLV) canine distemper virus (CDV) vaccine has historically been recommended for animals in high-risk environments because of the rapid onset of immunity following vaccination. Recombinant CDV (rCDV) vaccine was deemed a suitable alternative to MLV-CDV vaccination in pet dogs, but insufficient data precluded its use where CDV was a serious threat to puppies, such as in shelters, kennels, and pet stores. In this study, dogs experimentally challenged hours after a single dose of rCDV or MLV vaccine became sick but recovered, whereas unvaccinated dogs became sick and died. Dogs vaccinated with a single dose of rCDV or MLV vaccine 1 week before being experimentally challenged remained healthy and showed no clinical signs. Dogs given one dose of rCDV vaccine hours before being placed in a CDV-contaminated environment did not become sick. These findings support the hypothesis that rCDV vaccine has a similar time-to-immunity as MLV-CDV vaccines and can likewise protect dogs in high-risk environments after one dose.     

Serologic response to a canarypox-vectored canine distemper virus vaccine in the giant panda (Ailuropoda melanoleuca).

The giant panda (Ailuropoda melanoleuca) is known to be susceptible to natural infection with canine distemper virus (CDV). Vaccination of giant pandas with conventional modified live CDV vaccines has been avoided due to the numerous carnivore species known to have become infected with CDV after vaccination. Serum-neutralizing antibodies to CDV were measured after s.c. and i.m. annual vaccination with a canarypox-vectored recombinant CDV vaccine in an adult male and female giant panda over the period of 2 yr. The vaccine proved to be safe, and serum-neutralizing antibody titers interpreted as protective against CDV disease were measured in each animal.     

犬瘟热的诊断及其预防免疫的研究进展

本文对犬瘟热（CD）的诊断、预防免疫和免疫失败的影响因素及犬瘟热病毒（CDV）的宿主范围进行了综述。CDV不仅感染陆生食肉动物，而且也感染水生食肉动物，并且其宿主范围还在不断扩大。CDV感染主要采用病毒分离、特异性病毒抗原或特异性核酸检测等方法确诊。疫苗包括灭活的CDV疫苗、麻疹病毒（MV）异源苗及CDV弱毒活苗。疫苗接种犬的免疫反应主要取决于毒株特性及犬的应答能力，只有弱毒活苗能诱导产生持久而坚强的保护力。尽管多年来CDV弱毒活苗的使用控制了CD的发生，但最近免疫过的犬发生CD的病例并不少见。分析免疫失败的原因，主要是母源抗体干扰、疫苗质量差、其它病毒的免疫抑制以及CDV流行株可能发生了变异等因素的影响。     

Three-year rabies duration of immunity in dogs following vaccination with a core combination vaccine against canine distemper virus, canine adenovirus type-1, canine parvovirus, and rabies virus

Thirty-two seronegative pups were vaccinated at 8 weeks of age with modified-live canine distemper virus (CDV), canine adenovirus type-2 (CAV-2), and canine parvovirus (CPV) vaccine and at 12 weeks with a modified-live CDV, CAV-2, CPV, and killed rabies virus vaccine. An additional 31 seronegative pups served as age-matched, nonvaccinated controls. All test dogs were strictly isolated for 3 years after receiving the second vaccination and then were challenged with virulent rabies virus. Clinical signs of rabies were prevented in 28 (88%) of the 32 vaccinated dogs. In contrast, 97% (30 of 31) of the control dogs died of rabies infection. These study results indicated that no immunogenic interference occurred between the modified-live vaccine components and the killed rabies virus component. Furthermore, these results indicated that the rabies component in the test vaccine provided protection against virulent rabies challenge in dogs 12 weeks of age or older for a minimum of 3 years following vaccination.     

Effects of chloramphenicol on the development of immune responses to canine distemper virus in Beagle pups

The effect of oral chloramphenicol (CHPC) on the development of immune responses to canine distemper virus (CDV) in Beagle pups was studied. Dogs were treated with CHPC for 14 days at a dose of 50 mg/kg, three times a day. Hematologic changes in CHPC-treated dogs included: polychromasia, anisocytosis, and target cell formation of red blood cells concurrent with vacuolation of lymphocytes and basophilic granule formation in neutrophils. Dogs given this therapy showed normal in vivo and in vitro immune responses after CDV vaccination and survived a virulent CDV challenge, whereas untreated, unvaccinated dogs became ill or died after challenge exposure. The results of this study indicate that CHPC therapy does not interfere with either the prechallenge immune response to attenuated viral antigen or the efficient immune mechanisms invoked during virulent virus challenge.     

Mass mortality in seals caused by a newly discovered morbillivirus

During a recent disease outbreak among harbour seals (Phoca vitulina) in the North and Baltic seas, more than 17,000 animals have died. The clinical symptoms and pathological findings were similar to those of distemper in dogs. Based on a seroepizootiological study, using a canine distemper virus (CDV) neutralization assay, it was shown that CDV or a closely related morbillivirus (phocid distemper virus-PDV) was the primary cause of the disease. The virus was isolated in cell culture from the organs of dead seals and characterized as a morbillivirus by serology (immunofluorescence neutralization and enzyme-linked immunosorbent assays) and by negative contrast electron microscopy. Experimental infection of SPF dogs resulted in the development of mild clinical signs of distemper and CDV-neutralizing antibodies. The disease was reproduced in seals by experimental inoculation of organ material from animals that had died during the outbreak. However, seals that had been vaccinated with experimental inactivated CDV vaccines were protected against this challenge. This fulfilled the last of Koch's postulates, confirming that the morbillivirus isolated from the seal organs, was the primary cause of the disease outbreak. The recent demonstration of the presence of a similar virus in Lake Baikal seals (Phoca sibirica), which infected these Siberian seals 1 year before the northwestern European seals were infected, raises new questions about the origin of this infectious disease in pinnipeds.     

Three-year duration of immunity in dogs following vaccination against canine adenovirus type-1, canine parvovirus, and canine distemper virus

A challenge-of-immunity study was conducted to demonstrate immunity in dogs 3 years after their second vaccination with a new multivalent, modified-live vaccine containing canine adenovirus type 2 (CAV-2), canine parvovirus (CPV), and canine distemper virus (CDV). Twenty-three seronegative pups were vaccinated at 7 and 11 weeks of age. Eighteen seronegative pups, randomized into groups of six dogs, served as challenge controls. Dogs were kept in strict isolation for 3 years following the vaccination and then challenged sequentially with virulent canine adenovirus type 1 (CAV-1), CPV, and CDV. For each viral challenge, a separate group of six control dogs was also challenged. Clinical signs of CAV-1, CPV, and CDV infections were prevented in 100% of vaccinated dogs, demonstrating that the multivalent, modified-live test vaccine provided protection against virulent CAV-1, CPV, and CDV challenge in dogs 7 weeks of age or older for a minimum of 3 years following second vaccination.     

Vaccine-associated canine distemper infection in a litter of African hunting dogs (Lycaon pictus)

Four, 57 days old, African hunting dog puppies (Lycaon pictus) from one litter died within three weeks following vaccination with modified-live canine distemper virus (CDV) and killed canine adenovirus type 1, canine parvovirus and Leptospira icterohemorrhagiae and canicola. 18 days post vaccination, the animals developed neurologic disease characterized by episodes of grand mal seizures and circling. Macroscopic, histological and immunohistochemical studies revealed acute systemic CDV infection with acute encephalopathy. Virus isolation attempts using primary dog kidney cells, lung macrophages and Vero cells were negative. Therefore, the question whether the infection was the result of vaccination or natural infection remains open. The benefits and risks regarding the use of modified-live CDV vaccines and killed canine distemper vaccines in exotic carnivores are briefly discussed.     

表达犬瘟热病毒H基因重组新城疫病毒的构建及其免疫原性研究

为研制安全、有效的新型犬瘟热疫苗,本研究利用新城疫病毒(NDV) LaSota弱毒疫苗株反向遗传操作系统,构建出表达犬瘟热病毒(CDV)弱毒疫苗株Rockborn-20/8血凝素(H)蛋白的重组病毒rLa-CDV-H,并对其生物学特性进行鉴定,评估其作为犬瘟热活载体疫苗的安全性和有效性.通过免疫荧光和western blot试验证明了CDV H蛋白的正确表达;重组病毒株保持了LaSota亲本株的低致病性和高滴度鸡胚生长特性;重组病毒rLa-CDV-H接种12周龄比格犬后,可以诱导显著的CDV中和抗体反应.本研究表明重组病毒rLa-CDV-H具有作为犬瘟热重组病毒活载体疫苗的潜力.     

Effects of prednisolone on the development of immune responses to canine distemper virus in beagle pups

Effects of oral prednisolone (OP) on the development of immune responses of Beagle pups to canine distemper virus (CDV) were studied. Dogs were treated with OP for 21 days, twice a day for the first 7 days, once a day for the next 7 days, and on alternate days for the last 7 days. Dogs given dosages of OP (1 mg/kg and 10 mg/kg) showed a normal in vivo immunogenic response after CDV vaccination and survived a virulent CDV challenge exposure, whereas non-treated, nonvaccinated dogs became ill or died after challenge exposure. The most marked effect of corticosteroid treatment on the immune system was the graded phytoimmunosuppressive effect upon the lymphocyte blast transformation test.     

Canine parvovirus type 2 vaccine protects against virulent challenge with type 2c virus

The ability of dogs vaccinated with a live attenuated CPV type 2 (Nobivac Intervet) vaccine to resist challenge with a current CPV2c isolate was investigated. Six SPF beagle dogs were given the minimum recommended course of vaccination, comprising a single inoculation of vaccine (Nobivac Lepto+Nobivac Pi) at 8-10 weeks of age followed 3 weeks later with a parvovirus vaccine in combination with distemper, adenovirus and parainfluenza virus (Nobivac DHPPi) and a repeat leptospirosis vaccine. Six control dogs were kept unvaccinated. All animals were challenged orally with a type 2c isolate of CPV and monitored for clinical signs, virus shedding, white blood cell fluctuations and serological responses. All vaccinated dogs were fully protected; showing no clinical signs nor shedding challenge virus in the faeces, in contrast to control animals, which displayed all the typical signs of infection with pathogenic CPV and shed challenge virus in the faeces.     

犬瘟热的临床诊断技术与疫苗研究进展

犬瘟热是由犬瘟热病毒引起的犬科、鼬科和浣熊科等动物的一种高度接触性烈性传染病。该病在临床上可根据临床症状和流行特点作出初步诊断,结合病原学检查和血清学诊断即可确诊。目前一直缺少治疗犬瘟热的有效药物,所以犬瘟热的预防主要依靠接种疫苗。结合已有研究报道,总结了犬瘟热的临床诊断技术和犬瘟热疫苗方面的研究进展,以期为兽医同仁提供参考。     

Pathogenesis of two strains of lion (Panthera leo) morbillivirus in ferrets (Mustela putorius furo)

Canine distemper virus (CDV) was previously considered to have a host range restricted to the canid family. In 1994, the virus was associated with sporadic outbreaks of distemper in captive felids. However, after severe mortality occurred in the Serengeti lions (Panthera leo), attention became focused on the pathogenesis of the virus and a concerted effort was made to identify the virus as CDV or a closely related feline morbillivirus. The present study was designed to explore the susceptibility of ferrets to challenge with two morbilliviruses isolated from lions and the protective effects of a modified-live mink distemper vaccine. Because mortality in ferrets infected with pathogenic CDV approaches 100%, the ferret was selected as a test animal. Two strains of lion morbillivirus were used as a challenge, A92-27/20 (California lion isolate) and A94-11/13 (Serengeti lion isolate). The two strains of lion morbillivirus were antigenically related to CDV (Rockborn strain), and ferrets were susceptible to both of the viruses when inoculated intraperitoneally. The inoculated ferrets were anorectic at 5-6 days postinoculation (PI), exhibited oculonasal discharge at 9-12 days PI, and became moribund at 12-22 days PI. Severe bilateral conjunctivitis was the typical clinical sign. Inclusion bodies characteristic of morbillivirus (eosinophilic, intranuclear, and intracytoplasmic) were distributed in many epithelial cells, including those of the skin, conjunctiva, gallbladder, liver, pancreas, stomach, trachea, lung, urinary bladder, and kidney. Virus was reisolated from selected lung tissues collected at necropsy and identified by CDV-specific immunofluorescence. Ferrets vaccinated with the mink distemper vaccine (Onderstepoort strain) were protected from challenge with the two lion strains, adding further support to the premise that the viruses are closely related to CDV.     

Comparative analyses of canine distemper viral isolates from clinical cases of canine distemper in vaccinated dogs

Sequence and phylogenetic analyses of three isolates of canine distemper virus (CDV) isolated from three dogs with a vaccination history were compared with the same analyses of vaccine virus isolated from a vaccine used for dogs. The three dogs showed clinical signs of a recent major type of CD in Japan, including oculonasal discharge and diarrhea, and pathological findings including non-suppurative encephalitis, pneumonia, mild gastroenteritis and lymphoid depletion. Inclusion bodies were in the stomach without inflammation and encephalitis was without clinical signs. One of the highest titers of CDV in different organs of the three dogs was commonly systemic lymphatic organs, including the spleen, lymph nodes and tonsils. New isolates of CDV joined to the clades of the Asia 1 group that is far from the vaccine group. These results surely indicate that wild strains of CDV from dogs with a vaccination history were not reversed vaccine virus, and that the dogs showed characteristics of recent CD in Japan.     

水貂犬瘟热Vero细胞活疫苗(CDV3-CL株,悬浮培养)临床安全性和免疫效力评价

为评价水貂犬瘟热Vero细胞活疫苗(CDV3-CL株,悬浮培养)冻干制剂在临床应用中的安全性和免疫效果,分别在吉林、辽宁两省选择饲养规模相似的3个毛皮兽场进行疫苗安全性(10头份)和免疫效力实验(1头份)研究,接种后观察动物的临床症状,检测抗体水平并随机选择部分水貂进行攻毒试验。结果显示,超剂量接种水貂未见有明显的临床症状,对水貂的生产性能无明显影响;水貂免疫疫苗后21 d即可获得达到免疫保护的抗体水平;免疫180 d仍能维持较高水平的抗体,且能够保护动物抵抗强毒攻击。试验表明,水貂犬瘟热Vero细胞活疫苗(CDV3-CL株,悬浮培养)冻干制剂具有较好的临床保护效果。     

Serologic response of domestic ferrets (Mustela putorius furo) to canine distemper and rabies virus vaccines

Nine unrelated 12-week-old naive domestic ferrets (Mustela putorius furo) were used to evaluate the serologic responses to commercial canine distemper virus (CDV) and rabies virus (RV) vaccines. Five of the ferrets (group 1) were inoculated 3 times at 2-week intervals with a multivalent modified-live virus vaccine of canine cell-line origin, containing CDV and an inactivated RV vaccine. Four of the ferrets (group 2) were inoculated once with the multivalent modified-live virus vaccine containing CDV and were not inoculated with the RV vaccine. Both group-1 and group-2 ferrets seroconverted to the CDV component of the vaccine. Group-1 ferrets also seroconverted after RV vaccination and maintained serum antibody titers to both CDV and RV for at least 7 months. Domestic ferret sera were found to have IgG epitopes similar to sera of domestic dogs and cats. Domestic ferret sera did not contain antibodies to feline coronavirus or FeLV antigens.     

Influence of vaccination route on the efficacy of Aujeszky's disease deletion-mutant vaccine.

In order to compare the effect of the route of immunization on the efficacy of a modified live Aujeszky's disease (AD) vaccine, which had deletions in both thymidine kinase (TK-) and glycoprotein gIII genes (gpIII-), 20 six-week-old pigs were vaccinated by either the intramuscular (IM) (n = 10) or subcutaneous (SC) (n = 10) route. All the animals, including five non-vaccinated control animals, were challenged with virulent AD virus 22 days after vaccination. Four of five non-vaccinated animals died within 12 days after challenge. Although none of vaccinated animals died, three of animals in the SC group exhibited clinical signs, and average daily gains in the SC group were depressed. The animals in the IM group were not found to shed challenge virus, but those in the SC group shed the virus up to 9 days. Virus neutralizing antibody titers in the vaccinated animals were low or non-detectable by 21 days after vaccination. A glycoprotein gII (gpII) screening ELISA detected gpII antibody in all animals in the IM group. While, only 30% of animals in the SC group were positive by the same test. The results of this study indicate that TK-, gpIII modified live AD virus vaccine is effective against challenge with virulent AD virus; however, vaccination by the SC route reduced vaccine efficacy in comparison with IM route.     

Use of recombinant vaccinia-rabies virus for oral vaccination of fox cubs (Vulpes vulpes, L) against rabies

Thirteen fox cubs were orally administered 10(7.2) plaque-forming units of live vaccinia-rabies glycoprotein recombinant virus. On Day 28 post-vaccination, all but 1 cub had produced rabies virus antibodies. Twelve animals were intramuscularly inoculated with 10(3.2) mouse intracerebral LD50 of rabies virus suspension on Days 33 (5 foxes), 180 (4 foxes) or 360 (3 foxes) after vaccination. Eleven of them resisted rabies challenge. Unvaccinated foxes, either put in contact with 1 vaccinated animal or used as controls, died after challenge applied on Day 33. The absence of horizontal transmission of this vaccine strain and its innocuity to cubs were also demonstrated.