Duration of active and colostrum-derived passive antibodies to bovine viral diarrhea virus in calves.

Duration of active and colostrum-derived passive antibodies to bovine viral diarrhea virus was studied in 14 calves. Five calves born with actively induced antibodies to bovine viral diarrhea virus retained high titers during the year of observation. Colostrum-derived antibodies to bovine viral diarrhea virus in nine calves declined at an expected rate for the first four to six months of age. However, titers of six of these calves increased at five to eight months of age and either remained constant or increased through one year of age. Bovine viral diarrhea virus antibody titers of the other three calves declined at a constant rate to less than 1:4 by nine to 12 months of age.     

牛病毒性腹泻病毒弱毒活疫苗免疫持续期的研究

为检测牛病毒性腹泻病毒(BVDV)弱毒活疫苗在免疫牛体内抗体产生及其消长规律,评价弱毒疫苗的保护效力,并确定免疫持续期,本试验对免疫试验牛每头颈部肌肉接种BVDV SM株弱毒疫苗104.5TCID50,监测血清抗体效价,进行免疫持续期的确定。在疫苗免疫后的6个月、9个月和12个月,分别抽取5头免疫组和5头对照组牛,采用BVDV-JL强毒株进行攻毒试验,每头牛攻毒剂量为6×107.0TCID50/mL。结果显示疫苗免疫后12个月时血清中和抗体效价仍维持在1∶1048以上。攻毒结果显示,在3个不同时间点进行强毒攻击后,免疫组所有动物白细胞数量都没有下降也没有分离到病毒,而对照组动物白细胞数下降均超过30%,6个月和9个月时动物血清中均能分离到病毒,而12个月对照组动物由于年龄大,没有分离到病毒,因此暂定此疫苗的免疫持续期为9个月。     

牛病毒性腹泻弱毒活疫苗免疫持续期的研究

为检测牛病毒性腹泻病毒(BVDV)弱毒活疫苗在免疫牛体内抗体产生及其消长规律,评价弱毒疫苗的保护效力,并确定免疫持续期,本试验对免疫试验牛每头颈部肌肉接种BVDV SM株弱毒疫苗10^4.5TCID₅₀/头,监测血清抗体效价,进行免疫持续期的确定。在疫苗免疫后的6、9和12个月分别抽取5头免疫组和5头对照组牛采用BVDV-JL强毒株进行攻毒试验,每头牛攻毒剂量为6×10^7.0 TCID₅₀/mL。结果显示疫苗免疫后12个月时血清中和抗体效价仍维持在1∶1048以上,攻毒结果显示3个时间点强毒攻击后,免疫组所有动物白细胞数量都没有下降也没有分离到病毒,而对照组动物白细胞数下降均超过30%,6和9个月动物均分离到病毒,而12个月对照组动物由于年龄大,没有分离到病毒,因此暂定此疫苗的免疫持续期为9个月。     

A study of some pathogenetic aspects of bovine viral diarrhea virus infection

The cytopathic (CP) TVM-2 strain of bovine viral diarrhea virus (BVDV) induced in calves a severe disease, characterized by the clinical picture which is usually reported for the acute primary infection observed under natural conditions. In contrast, the calves inoculated with a different biotype of BVDV, the non-cytopathic (NCP) New York-1 strain, remained clinically normal with the only evidence of virus replication in these calves being the recovery of the virus from their pharyngeal swabbings and blood and also the detection of specific neutralizing antibody in their serums. When calves were immunosuppressed with dexamethasone (DMS), they underwent an overt systemic disease of such a severity that in most of the cases it ended with the death of the animals. This result was obtained with either the CP and the NCP strain of BVDV. Finally, the mixed infection that was obtained in the calves with the CP and the NCP BVDV did not result in any particular unexpected pathological situation. It was speculated that the immunosuppressive activity of BVDV could be a property peculiar to certain isolates of the virus.     

Differences in virulence between two noncytopathic bovine viral diarrhea viruses in calves.

A noncytopathic bovine viral diarrhea virus (BVDV), BVDV-890, isolated from a yearling heifer that died with extensive internal hemorrhages, was compared for virulence in calves with noncytopathic BVDV-TGAN, isolated from an apparently healthy persistently infected calf. After challenge exposure with BVDV-890, nonimmune calves (n = 7) developed fever > 40 C, diarrhea, leukopenia, lymphopenia, neutropenia, and thrombocytopenia. Most calves (n = 6) died or were euthanatized by 19 days after challenge exposure. Challenge exposure with BVDV-890 did not induce disease in 2 calves that had congenital persistent infection with BVDV or in 3 calves that had neutralizing antibody titer > 4 against BVDV-890. After challenge exposure with BVDV-TGAN, nonimmune calves (n = 7) developed fever > 40 C and, rarely, diarrhea or lymphopenia. All of those calves survived challenge exposure. The average maximal titer of BVDV-890 isolated from serum was 1,000 times that of BVDV-TGAN. In calves infected with BVDV-890, the average maximal percentages of lymphocytes and platelets associated with virus were greater than those found in calves infected with BVDV-TGAN. Additional findings of epidemiologic significance were prolonged shedding of virus and delayed production of viral-neutralizing antibody in 1 calf challenge-exposed with BVDV-890. Also, after production of neutralizing antibody, mutant virus that was refractory to neutralization was isolated from calves challenge-exposed with BVDV-TGAN.     

Prolonged excretion and failure of cross-protection between distinct serotypes of bovine rotavirus

Four newborn calves were experimentally infected with two distinct serotypes of bovine rotavirus (BRV-1 and BRV-2). Initially, three colostrum-deprived calves were inoculated orally with either BRV-1 or BRV-2; all developed severe diarrhea and produced serotype-specific neutralizing antibodies. Fecal virus was first demonstrated by immunofluorescence the day after inoculation. The virus titers reached a maximum of 10(5.2)-10(6.6) fluorescent focus forming units g-1 of feces 2-5 days after inoculation and then decreased. Fecal virus was detected in low titers beyond 28 days after inoculation despite the development of serum neutralizing antibodies. One calf, which had acquired specific active immunity against BRV-1 following oral infection, was further infected orally with BRV-2 4 weeks later. The calf again manifested diarrhea, excreted BRV-2 and showed an increase in serum neutralizing antibody against BRV-2. These results indicated that calves infected with either BRV-1 or BRV-2 do not have cross-protection to infection with heterologous BRV, and that recurrence of the disease can occur. The possible mechanisms of the persistence of BRV in calves and its role in the epidemiology of this infection are discussed.     

Comparison of levels and duration of detection of antibodies to bovine viral diarrhea virus 1, bovine viral diarrhea virus 2, bovine respiratory syncytial virus,bovine herpesvirus 1, and bovine parainfluenza virus 3 in calves fed maternal colostrum or a colostrum-replacement product

Colostrum-replacement products are an alternative to provide passive immunity to neonatal calves; however, their ability to provide adequate levels of antibodies recognizing respiratory viruses has not been described. The objective of this study was to compare the serum levels of IgG at 2 d of age and the duration of detection of antibodies to bovine viral diarrhea virus 1 (BVDV-1), bovine viral diarrhea virus 2 (BVDV-2), bovine respiratory syncytial virus (BRSV), bovine herpesvirus 1 (BHV-1), and bovine parainfluenza virus 3 (BPIV-3) in calves fed maternal colostrum (MC) or a colostrum replacement (CR) at birth. Forty newborn male Holstein calves were assigned to the CR or the MC group. Group CR (n = 20) received 2 packets of colostrum replacement (100 g of IgG per 470-g packet), while group MC (n = 20) received 3.8 L of maternal colostrum. Blood samples for detection of IgG and virus antibodies were collected from each calf at birth, at 2 and 7 d, and monthly until the calves became seronegative. Calves in the MC group had greater IgG concentrations at 2 d of age. The apparent efficiency of absorption of IgG was greater in the MC group than in the CR group, although the difference was not significant. Calves in the CR group had greater concentrations of BVDV neutralizing antibodies during the first 4 mo of life. The levels of antibodies to BRSV, BHV-1, and BPIV-3 were similar in the 2 groups. The mean time to seronegativity was similar for each virus in the 2 groups; however, greater variation was observed in the antibody levels and in the duration of detection of immunity in the MC group than in the CR group. Thus, the CR product provided calves with more uniform levels and duration of antibodies to common bovine respiratory viruses.     

Investigation of an outbreak of mucosal disease in a beef cattle herd in southwestern Saskatchewan.

This study describes the epidemiological investigation of an outbreak of mucosal disease that occurred on a ranch in southwestern Saskatchewan. Over a six-month period during the fall and winter of 1991-1992, in a herd of 515 beef cattle and 96 bison, 20 yearling cattle from a group of 105 housed in one feedlot pen died from mucosal disease. A further eight yearlings were slaughtered for salvage because they were at risk of dying from mucosal disease. Mucosal disease mortalities were the first observed evidence of fetal infections with bovine viral diarrhea virus in this herd. Animals that died from mucosal disease exhibited signs of ill thrift prior to death. Deaths from mucosal disease were confined to the progeny of one herd of beef cows. Following an outbreak of fetal infection with bovine viral diarrhea virus during 1989-1990, at least 28 (22%) of the 128 calves born from this herd of cows in the spring of 1990 were persistently infected with bovine viral diarrhea virus. However, only one calf born from this herd in 1991, and five calves born from all herds in 1992 were persistently infected. Of the five persistently infected calves born in 1992, three were born to persistently infected replacement heifers born in 1990. These heifers calved without assistance in 1992, but only one of their calves survived past three days of age, and it was persistently infected. In January 1992, 82% of the total herd had reciprocal antibody titers to bovine viral diarrhea virus of > or = 1024 which suggested a high level of herd immunity to bovine viral diarrhea virus.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vitro and in vivo immune responses in neonatally thymectomized holstein-friesian calves exposed to bovine viral diarrhea virus

Neonatally thymectomized and normal Holstein-Friesian calves were exposed to bovine viral diarrhea virus and challenged 22 days later. Baseline values in non-specific mitogen induced lymphocyte blastogenesis and serologic responses to tetanus toxoid and Brucella abortus strain 19 were established in neonatally thymectomized and normal calves.Neither viral recovery nor protective antibody production followed the very low level primary exposure to bovine viral diarrhea virus. The expected clinical response to an appropriate challenge inoculum did not occur, however, suggesting an immune response to bovine viral diarrhea virus had been initiated by the primary exposure. Five of eight calves developed protective serum levels of bovine viral diarrhea antibody. This may represent an example of immunologic priming. Exposure to low levels of bovine viral diarrhea virus also has potential implications in the pathogenesis of chronic bovine viral diarrhea wherein low level exposure may interfere with the development of protective levels of bovine viral diarrhea antibody as was observed in three calves.Circulating lymphocyte concentrations and results of non-specific mitogen stimulation of lymphocytes revealed a reduced phytohemagglutinin response in conjunction with a slightly increased response to bacterial lipopolysaccharide and pokeweed mitogen in the presence of moderate lymphopenia. The capacity of lymphocytes to respond to phytohemagglutinin was unchanged but an increased total response, as occurred in control thymectomized and intact calves, did not occur.The response to tetanus toxoid, a thymus-independent antigen, was increased following exposure to bovine viral diarrhea virus, perhaps reflecting an alteration in thymic-independent regulation. The lack of a differential response to Brucella abortus strain 19 implied competence in thymus-dependent helper cells.     

Characterization of protection from systemic infection and disease by use of a modified-live noncytopathic bovine viral diarrhea virus type 1 vaccine in experimentally infected calves

OBJECTIVE: To evaluate protection against systemic infection and clinical disease provided by use of a modified-live noncytopathic bovine viral diarrhea virus (BVDV) type 1 vaccine in calves challenged with NY-1 BVDV. ANIMALS: 10 calves, 5 to 7 months of age. PROCEDURES: Calves were allocated (n = 5/group) to be nonvaccinated or vaccinated SC on day 0 with BVDV type 1 (WRL strain). Calves in both groups were challenged intranasally with NY-1 BVDV on day 21. Calves' rectal temperatures and clinical signs of disease were recorded daily, total and differential WBC and platelet counts were performed, and serum neutralizing antibody titers against NY-1 BVDV were determined. Histologic examinations and immunohistochemical analyses to detect gross lesions and distribution of viral antigens, respectively, were performed. RESULTS: After challenge exposure to NY-1 BVDV, nonvaccinated calves developed high rectal temperatures, increased respiratory rates, viremia, leukopenia, lymphopenia, and infection of the thymus. Vaccinated calves did not develop high rectal temperatures or clinical signs of respiratory tract disease. Vaccinated calves appeared to be protected against systemic replication of virus in that they did not develop leukopenia, lymphopenia, viremia, or infection of target organs, and infectious virus was not detected in peripheral blood mononuclear cells or the thymus. CONCLUSIONS AND CLINICAL RELEVANCE: The modified-live BVDV vaccine protected calves against systemic infection and disease after experimental challenge exposure with NY-1 BVDV. The vaccine protected calves against infection and viremia and prevented infection of target lymphoid cells.     

Immunofluorescence of bovine virus diarrhea viral antigen in white blood cells from experimentally infected immunocompetent calves.

A study to evaluate the detection of bovine virus diarrhea viral antigen using immunofluorescence testing of white blood cells was conducted. Five colostrum-deprived calves were inoculated intravenously with a cytopathic strain of the virus. Lymphocyte and buffy coat smears were prepared daily for direct immunofluorescent staining for detection of antigen. Lymphocytes were separated from heparinized blood using a Ficoll density procedure. Buffy coat smears were prepared from centrifuged blood samples collected using ethylenediaminetetraacetic acid as an anticoagulant. Bovine viral diarrhea virus antigen was detected by immunofluorescence between 3 and 11 days postinfection in lymphocyte smears and 3 to 12 days postinfection in buffy coat smears. Isolation of virus from both lymphocytes and buffy coat preparations correlated with detection of immunofluorescence. Serum neutralizing antibody to bovine virus diarrhea virus was detected on day 10 postinfection. Buffy coat smears were as sensitive as lymphocyte smears for the detection of antigen by immunofluorescence. It appeared that immunofluorescent staining of white blood cells was an effective method of detecting bovine virus diarrhea viral antigen.     

Effect of maternal antibody upon vaccination with infectious bovine rhinotracheitis and bovine virus diarrhea vaccines.

This report presents the normal rate of decay of maternal antibody and the influence of maternal antibody on responses to a single vaccination with modified-live bovine virus diarrhea and infectious bovine rhinotracheitis virus vaccines at 196 days of age and on response to vaccinations with the same vaccines given twice at 84 and 196 days of age. Passive immunity decreased to near zero over the first six months of life for both bovine virus diarrhea and infectious bovine rhinotracheitis controls. All calves seroconverted to bovine virus diarrhea vaccine at 84 days of age, even though high levels (greater than 1:32) of maternal antibodies were present. These calves did not seroconvert to infectious bovine rhinotracheitis vaccine at 84 days of age when high levels (less than 1:16) of maternal antibodies were present. Calves responded well to bovine virus diarrhea and infectious bovine rhinotracheitis vaccines given only once at 196 days of age after passive immunity disappeared. Calves which were revaccinated with infectious bovine rhinotracheitis seroconverted showing a more rapid response than the single vaccinates. Those revaccinated with bovine virus diarrhea showed an immediate response of small magnitude.     

Association of bovine viral diarrhea virus with multiple viral infections in bovine respiratory disease outbreaks

We investigated eleven outbreaks of naturally occurring bovine respiratory diseases in calves and adult animals in the St-Hyacinthe area of Quebec. Specific antibodies to bovine herpesvirus-1, bovine viral diarrhea virus, respiratory syncytial virus, parainfluenza type 3 virus, reovirus type 3, and serotypes 1 to 7 of bovine adenovirus were found in paired sera from diseased animals. Several bovine viruses with respiratory tropism were involved concomitantly in herds during an outbreak of bovine respiratory disease. In addition, concomitant fourfold rises of antibody titers were frequently observed to two or more viral agents in seroconverted calves (61%) or adult animals (38%). Bovine viral diarrhea virus was found to be the most frequent viral agent associated with multiple viral infection in calves only (92%).     

Correlation between maternal serum antibodies and protection against bovine rotavirus diarrhea in calves

The correlation between maternal serum antibodies in beef calves at 2 days old and protection against diarrhea induced by natural bovine rotavirus (BRV) infection was examined. Virus neutralizing (VN) antibody titers against BRV in sera from calves that developed diarrhea by BRV infection within 14 days of age (BRV-diarrheal calves) were significantly lower than those from calves that had no diarrhea. In the BRV-diarrheal calves, a positive correlation was found between the VN antibody titers and age of the onset of diarrhea. There were negative correlations between the VN antibody titers and duration of the diarrhea, VN antibody titers and cumulative diarrhea scores, and the VN antibody titers and duration of virus shedding. These results suggest that the VN antibody titers against BRV in newborn calf serum could be an indicator of protection against BRV-induced diarrhea.     

Thrombocytopenia and hemorrhages in veal calves infected with bovine viral diarrhea virus

The relationship between bovine viral diarrhea virus (BVDV) infection and thrombocytopenia was studied in 18 veal calves experimentally infected with BVDV. All calves were free of BVDV, and 13 calves were free of serum neutralizing antibodies to BVDV before virus inoculation. Calves were inoculated at approximately 10 days of age, and platelet counts were monitored over a period of several weeks. Ten additional calves housed in close proximity were kept as uninoculated controls. A profound decrease in platelet counts by 3 to 11 days after inoculation was seen in all calves that had neutralizing antibody titers less than 1:32 before infection. Severe thrombocytopenia (less than 5,000 platelets/microliter) was seen in 12 calves, 11 of which also developed hemorrhages. Necropsy findings in 3 severely thrombocytopenic calves that died included multiple hemorrhages throughout the body. Calves that recovered had increased platelet counts, and in most instances, a corresponding increase in neutralizing antibody titers to BVDV. At 11 days after inoculation, BVDV was detected on platelets by use of immunofluorescence, but evidence of surface-bound immunoglobulin was not found. The results suggest that a nonimmunoglobulin-mediated method of platelet destruction or sequestration develops as a sequela to BVDV infection.     

Effect of levamisole on induced bovine viral diarrhea

The effect of levamisole in calves experimentally infected with bovine viral diarrhea virus was evaluated in a double-blind study. The infection was mild and there was no difference in severity of infection or speed of recovery between levamisole-treated and 0.9% NaCl solution-treated (control) calves. Also, the serum antibody titers and viral recovery data of these calves were comparable. The white blood cell counts were consistently higher in the treated group than in the control group, with the difference peaking on postinoculation day 15. The detection of marked lymphopenia in control calves but not in levamisole-treated calves indicated a potential use of levamisole in bovine viral diarrhea.     

Virological Examination of Bovine Mammary Lymph Nodes

Mammary lymph nodes from 42 Hereford cows culled for poor reproductive performance were examined for cytopathogenic virus and hemadsorption. No evidence of viral infection was detected using the methods employed. Serum from all the animals gave positive reactions to the hemagglutination-inhibition test for bovine myxovirus parainfluenza 3. Six of 12 had neutralizing antibody against bovine virus diarrhea virus, but none of the 12 had neutralizing antibodies against infectious bovine rhinotracheitis virus.     

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.     

Effect of passive immunity on the development of a protective immune response against bovine viral diarrhea virus in calves

OBJECTIVE: To determine whether passively acquired antibodies prevent development of a protective immune response to live virus in calves. ANIMALS: 18 calves. PROCEDURES: Calves were caught immediately after birth and tested free of bovine viral diarrhea virus (BVDV) and serum antibodies against BVDV. Within 48 hours, 12 calves were fed colostrum that contained antibodies against BVDV and 6 calves received BVDV antibody free milk replacer. Three milk replacer fed and 6 colostrum fed calves were exposed to virulent BVDV2-1373 at 2 to 5 weeks of life when passively acquired serum antibody titers were high. After serum antibody titers against BVDV had decayed to undetectable concentrations (at 7 to 9 months of age), the 3 remaining milk replacer fed calves, 6 colostrum fed calves previously exposed to BVDV2-1373, and 6 colostrum fed calves that had not been exposed to the virus were inoculated with BVDV2-1373. RESULTS: Passively acquired antibodies prevented clinical disease in inoculated colostrum fed calves at 2 to 5 weeks of life. Serum antibody titers did not increase in these calves following virus inoculation, and serum antibody titers decayed at the same rate as in noninoculated colostrum fed calves. Inoculated colostrum fed calves were still protected from clinical disease after serum antibody titers had decayed to nondetectable concentrations. Same age colostrum fed calves that had not been previously exposed to the virus were not protected. CONCLUSIONS AND CLINICAL RELEVANCE: A protective immune response was mounted in calves with passive immunity, but was not reflected by serum antibodies titers. This finding has implications for evaluating vaccine efficacy and immune status.     

Natural infection of pigs with bovine viral diarrhea virus and its differential diagnosis from hog cholera.

Natural infection of pigs with bovine viral diarrhea virus (BVDV) through contact with infected cattle has caused problems in diagnosing hog cholera (HC). Low cross-reacting serum antibody titers against HC caused by BVDV infection were found in clinically normal pigs as well as those suspected of having HC. Bovine viral diarrhea virus was isolated from specimen tissues and initially identified as HC virus (HCV), using the fluorescent antibody cell culture technique. Additional cell cultures, as well as pig and calf trials, were necessary to identify it as BVDV. The isolate caused clinical signs of illness in the calves, whereas the pigs remained healthy. Bovine viral diarrhea virus may be detected in tissue sections or isolated in cell cultures and confirmed as HCV, using the HC fluorescent antibody conjugate. Laboratories performing the neutralization test for HC should use discretion when interpreting HC titers unless BVD titers are determined on the same serums.