The vaccination and challenge with bovine viral diarrhea virus (BVDV) of calves previously infected with a non-cytopathic BVDV.

Four calves were infected with noncytopathic (NCP) New York-1 strain of bovine viral diarrhea virus (BVDV). During the observation period of one month the calves remained clinically normal but the virus was repeatedly recovered from their pharyngeal swabbings and blood. Thirty days following infection the four calves were vaccinated, together with two uninfected calves, with a modified-live vaccine containing cytopathic (CP) BVDV, infectious bovine rhinotracheitis virus and parainfluenza-3 virus. No detrimental effects were observed after vaccination. Forty-three days after vaccination the calves were challenged by exposure either with the CP TVM-2 strain or the NCP New York-1 strain of BVDV. The vaccinated calves remained healthy throughout the 60-day observation period.     

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.     

Enhancement of infectious bovine keratoconjunctivitis by modified-live infectious bovine rhinotracheitis virus vaccine

The effects of a modified-live infectious bovine rhinotracheitis virus vaccine (administered ocularly or intranasally) on experimentally induced infectious bovine keratoconjunctivitis were evaluated. The modified-live infectious bovine rhinotracheitis virus vaccine was administered to 13 male Holstein calves (intranasally in 4 and ocularly in 9; day 0). Five calves were not vaccinated and served as controls. Calves were examined daily and, starting on day 4, Moraxella bovis was administered ocularly to all 18 calves once daily for 4 days. The eyes of all calves were assigned a clinical score, and the ocular secretions were evaluated for presence of infectious bovine rhinotracheitis virus and M bovis daily until day 19. The severity of the ocular lesions was estimated by scoring the lesions clinically and by determining the protein concentration, myeloperoxidase activity, and WBC count in the tears. By day 5, conjunctivitis, chemosis, and epiphora were observed in all of the calves vaccinated ocularly. The calves vaccinated intranasally developed conjunctival plaques, but did not develop chemosis or photophobia. All of the calves developed keratitis after inoculation with M bovis. The median lesion scores were greater in both groups of vaccinated calves than in the controls. Corneal perforations developed exclusively in the vaccinated calves. The frequency of M bovis isolation from ocular secretions was significantly (P less than 0.05) greater in the vaccinated calves than in the controls. The tears from the intranasally vaccinated calves contained the highest myeloperoxidase activity and WBC count. The mean protein concentration in the tears of vaccinated calves was not significantly different from that in tears of controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunization against bovine herpesvirus-1 infection. Preliminary tests in calves with a DNA vaccine

A bovine herpesvirus-1 (BHV-1) vaccine expressing glycoprotein D, the form with the transmembrane anchor removed, was evaluated for inducing immunity in calves. The plasmid encoding gD of BHV-1 was injected three times to nine calves, using three animals for each of the following routes: intramuscularly (i.m.), intradermally (i.d.), or intranasally (i.n.). Three additional calves were given the plasmid vector only and served as unvaccinated controls. When calves were subjected to challenge infection with BHV-1, all vaccinated calves as well as the controls developed a typical severe form of infectious bovine rhinotracheitis. However, compared to the controls, the vaccinated calves showed earlier clearance of challenge virus. Moreover, the calves given the vaccine i.m. developed neutralizing antibody to BHV-1 between 21 and 42 days following the first injection of vaccine, whereas in calves vaccinated either i.d. or i.n., as well as the controls, antibody first appeared in their sera 14 days post-challenge infection.     

Comparative serological response in calves to eight commercial vaccines against infectious bovine rhinotracheitis, parainfluenza-3, bovine respiratory syncytial, and bovine viral diarrhea viruses

A field trial was conducted to compare the serological responses in calves to eight commercial vaccines against infectious bovine rhinotracheitis virus (IBRV), parainfluenza-3 virus (PI3V), bovine respiratory syncytial virus (BRSV), and/or bovine viral diarrhea virus (BVDV). Calves given IBRV, P13V, BRSV, and BVDV vaccines had significantly higher antibodies to these viruses than unvaccinated controls; however, serological responses to killed BVDV vaccines were low. Calves with preexisting antibodies to IBRV, PI3V, BRSV, and the Singer strain of BVDV had lower seroconversion rates following vaccination than calves that were seronegative initially.

Serological responses in calves to IBRV, PI3V, BRSV, and BVDV differed among various commercial vaccines. Antibody titers to IBRV were higher in calves vaccinated with modified-live IBRV vaccines than in those vaccinated with killed IBRV vaccines. Following double vaccination with modified-live IBRV and PI3V vaccines, seroconversion rates and antibody titers to IBRV and PI3V were higher in calves vaccinated intramuscularly than in those vaccinated intranasally. Calves given Cattlemaster 4 had significantly higher titers to BRSV and PI3V, and lower titers to BVDV, than calves given Cattlemaster 3, suggesting that the addition of BRSV to Cattlemaster 4 caused some interaction among antigens.

     

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.     

Bovine recombinant interleukin-2 augments immunity and resistance to bovine herpesvirus infection

The in vivo administration of bovine recombinant interleukin-2 (rIL-2) was evaluated in calves vaccinated and then challenged with bovine herpesvirus-1 (BHV-1). In Experiment 1, 24 calves were allotted to four groups: control; bovine rIL-2; BHV-1 vaccine (modified-live); and bovine rIL-2 + BHV-1 vaccine. Serum neutralizing antibody titers to BHV-1 were increased sixfold, and virus shedding was fourfold less in calves vaccinated and treated with rIL-2 (25 micrograms/kg, intramuscularly) when compared to calves that received vaccine only. Treatment with rIL-2 induced lymphokine-activated killer activity that was eliminated by pretreating effector cells with complement and a monoclonal antibody (B26A) specific for the sheep red blood cell receptor. The rIL-2 treatment in BHV-1-vaccinated calves increased the calves' ability to withstand a BHV-1 challenge. However, during treatment with rIL-2, calves developed diarrhea and mild fever that abated after IL-2 treatment was stopped. A second experiment was then conducted to determine a dose of rIL-2 that would enhance immunity to BHV-1 without causing adverse side effects. Twenty-five calves were allotted to five groups that received injections of rIL-2 at 0.0, 25.0, 2.5, 0.25, or 0.025 micrograms kg-1 day-1 for 5 days. All calves received a modified-live BHV-1 vaccine. Calves treated with 25.0 micrograms kg-1 day-1 showed similar adverse side effects as in the first experiment but all other calves were normal. Compared to control calves, those treated with 25.0, 2.5, and 0.25 micrograms kg-1 day-1 of rIL-2 had higher (P less than 0.05) serum antibody titers to BHV-1 and following challenge lower (P less than 0.05) BHV-1 titers in nasal secretions; additionally, clinical disease as evidenced by nasal and ocular discharge was less severe (P less than 0.05). In vitro cytotoxic responses against BHV-1-infected bovine kidney cells were increased (P less than 0.05) in calves treated with rIL-2 in a dose dependent manner. These data suggest that bovine rIL-2 at 2.5 to 0.25 micrograms/kg may be an effective adjuvant to immunization.     

牛传染性鼻气管炎病毒LNM株致弱疫苗免疫效力的研究

为检测牛传染性鼻气管炎病毒(IBRV)抗体在免疫牛体内的产生及其消长规律,评价IBRV LNM株致弱疫苗的保护效力,并确定免疫持续期,本实验对免疫试验组牛每头颈部肌肉接种制备的IBRV LNM株致弱疫苗104.5 TCID50/mL,监测血清抗体效价,进行免疫期的确定。在疫苗免疫后的6个月、9个月和12个月分别抽取3头免疫组和两头对照组牛采用IBRV-LN01/08强毒株进行攻毒试验,每头牛的攻毒剂量为107.0 TCID50/mL。结果显示疫苗免疫后12个月时,中和抗体效价仍维持在1∶11以上。攻毒结果显示3个时间点强毒攻击后,疫苗对免疫牛均具有良好的保护力。研究表明IBRV弱毒疫苗可有效地保护免疫牛抵抗IBRV强毒株的攻毒,其免疫持续期最少为12个月。     

Effect of age at the time of vaccination on antibody titers and feedlot performance in beef calves

OBJECTIVE: To compare antibody responses, feedlot morbidity and mortality rates, feedlot performance, and carcass value for calves vaccinated with 1 of 2 vaccination strategies and for unvaccinated control calves. DESIGN: Randomized controlled clinical trial. ANIMALS: 451 beef steers and heifers. PROCEDURES: Calves were vaccinated with a modified-live infectious bovine rhinotracheitis virus (IBRV), bovine viral diarrhea virus types 1 (BVDV1) and 2 (BVDV2), parainfluenza type 3 virus, and bovine respiratory syncytial virus vaccine and Mannheimia haemolytica and Pasteurella multocida bacterin-toxoid at approximately 67 and 190 days of age (group 1; n = 151) or at approximately 167 and 190 days of age (group 2; 150) or were not vaccinated (control; 150). Serum antibody titers were measured at approximately 2, 67, 167, 190, and 232 days of age. Morbidity and mortality rates, feedlot performance, and carcass value were recorded for 361 calves shipped to feedlots. RESULTS: Percentages of calves seroconverting to IBRV, BVDV1, and BVDV2 were significantly higher for groups 1 and 2 than for the control group. Mean treatment costs were significantly lower for vaccinated than for control calves, and mean mortality rate was significantly higher for control calves than for group 1 calves. Feedlot performance and carcass value did not vary significantly among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that vaccination of beef calves with a 5-antigen modified-live virus vaccine at 67 and 190 days of age was as effective in terms of immunologic responses as was vaccination at 167 and 190 days of age.     

Induction of antigen-specific T-cell subset activation to bovine respiratory disease viruses by a modified-live virus vaccine

OBJECTIVE: To determine the efficacy of a modified-live virus vaccine containing bovine herpes virus 1 (BHV-1), bovine respiratory syncytial virus (BRSV), parainfluenza virus 3, and bovine viral diarrhea virus (BVDV) types 1 and 2 to induce neutralizing antibodies and cell-mediated immunity in na?ve cattle and protect against BHV-1 challenge. ANIMALS: 17 calves. PROCEDURES: 8 calves were mock-vaccinated with saline (0.9% NaCl) solution (control calves), and 9 calves were vaccinated at 15 to 16 weeks of age. All calves were challenged with BHV-1 25 weeks after vaccination. Neutralizing antibodies and T-cell responsiveness were tested on the day of vaccination and periodically after vaccination and BHV-1 challenge. Specific T-cell responses were evaluated by comparing CD25 upregulation and intracellular interferon-gamma expression by 5-color flow cytometry. Titration of BHV-1 in nasal secretions was performed daily after challenge. Results-Vaccinated calves seroconverted by week 4 after vaccination. Antigen-specific cell-mediated immune responses, by CD25 expression index, were significantly higher in vaccinated calves than control calves. Compared with control calves, antigen-specific interferon-gamma expression was significantly higher in calves during weeks 4 to 8 after vaccination, declining by week 24. After BHV-1 challenge, both neutralizing antibodies and T-cell responses of vaccinated calves had anamnestic responses to BHV-1. Vaccinated calves shed virus in nasal secretions at significantly lower titers for a shorter period and had significantly lower rectal temperatures than control calves. CONCLUSION AND CLINICAL RELEVANCE: A single dose of vaccine effectively induced humoral and cellular immune responses against BHV-1, BRSV, and BVDV types 1 and 2 and protected calves after BHV-1 challenge for 6 months after vaccination.     

The use of immunomodulators in the control of infectious bovine rhinotracheitis

Three experiments have been carried out to verify the effectiveness of an immunomodulator, Baypamun (Bayer AG) in limiting the spread of Bovine herpesvirus-1 (BHV-1), the causal agent of infectious bovine rhinotracheitis (IBR). In the first experiment, four calves infected with BHV-1 developed severe disease whereas four calves given Baypamun simultaneously with the virus had less severe disease. Four other calves in contact with the infected calves became severely ill but another four given Baypamun were only mildly affected. In the second experiment three calves infected with BHV-1, which reacted with typical disease, were allowed to remain in contact with six calves. All six calves were given Baypamun at various times following the exposure to BHV-1 infection and all showed a much reduced reaction with two treated for 4 days developing no clinical disease. Finally, in the third experiment one calf vaccinated one month before the start of the experiment did not develop any signs of disease when housed together with a calf experimentally infected with BHV-1. Of four other calves, vaccinated when the infected calf showed the first signs of disease, only the two given Baypamun in addition to the vaccine, were protected from clinical disease whereas the two given vaccine only developed classical signs of IBR. In the three experiments the virus shedding by the Baypamun-treated calves resulted to be significantly reduced.     

Vaccination of calves against bovine herpesvirus-1: assessment of the protective value of eight vaccines

Eight separate, but related experiments, were carried out in which groups of six calves were vaccinated with one of eight commercial vaccines. In each experiment the vaccinated calves were subsequently exposed to three calves infected with virulent bovine herpesvirus-1 (BHV-1). In each experiment, all infected donor calves developed a typical severe infectious bovine rhinotracheitis (IBR) infection and excreted virus in their nasal secretions of up to 10(8.00) TCID50/0.1 ml. One live BHV-1 gE-negative vaccine (A) and three modified live vaccines (B, C, D), administered intranasally, all protected against clinical disease. The calves vaccinated with one vaccine (C) also did not excrete virus in the nasal secretions, whereas the calves protected by vaccines A, B and D excreted virus in their nasal secretions but at low titres (10(0.66)-10(1.24) TCID50/0.1 ml). A fourth modified live vaccine (E), given intramuscularly, failed to prevent mild clinical disease in the calves which also excreted virus in the nasal secretions at titre of 10(1.00) TCID50/0.1 ml. An analogous result was given by the calves vaccinated with either of the two inactivated vaccines (F and G) or with a BHV-1 subunit vaccine (H). All calves developed mild clinical signs and excreted virus at titres of 10(2.20)-10(3.12) TCID50/0.1 ml. Calves vaccinated with C vaccine were subsequently given dexamethasone, following which virus was recovered from their nasal secretions. The virus isolates did not cause disease when calves were infected and appeared to be closely related to the vaccine strain.     

Reactivation of infectious bovine rhinotracheitis virus by transport

Transport was studied as a cause of reactivation of infectious bovine rhinotracheitis virus (Bovine herpesvirus-1; BHV-1) in heifers vaccinated 2-6 months before transport, using a double dose of the thermosensitive (ts) vaccine strain (Tracherine). Eight out of 19 animals showed ts strain re-excretion over a period of 1-3 days, beginning, in 5 out of the 8 heifers, the day after transport. In 14 other heifers, only sera were examined by sero-neutralisation: only 1 out of these 14 animals showed a rise in BHV-1 neutralising antibodies. Transport can therefore be considered as a stimulus of BHV-1 reactivation.     

A study on latency in calves by five vaccines against bovine herpesvirus-1 infection

Four bovine herpesvirus-1 (BHV-1) commercial vaccines, three of which (vaccines B, D, E) were modified live vaccines (MLV) and one (vaccine A) identified as a live strain of BHV-1 gE negative, were used for vaccination of calves, using three calves for each vaccine. Three months after vaccination calves were subjected to dexamethasone (DMS) treatment following which virus was recovered from calves inoculated with vaccine B and from those given vaccine D. No virus reactivation was obtained in calves, which received vaccines A or E. The DNA extracted from the two reactivated viruses was subjected to restriction endonuclease analysis. The restriction pattern of the isolate obtained from calves vaccinated with vaccine D differs significantly from that of the original vaccine, whereas the reactivated virus from calves given vaccine B conserved the general pattern of the original vaccine strain. For each reactivated virus in this experiment (B and D) as well as for the isolate obtained from calves vaccinated with a further MLV (vaccine C) in a previous trial, three calves were inoculated. No clinical signs of disease were detected in any of the inoculated calves during the observation period. When the nine calves were exposed 40 days later to challenge infection with virulent BHV-1, they remained healthy and no virus was isolated from their nasal swabbings. These results indicate that some BHV-1 vaccines considered in the project can establish latency in the vaccinated calves, however, the latency does not appear to interfere with the original properties of the vaccines in terms of safety and efficacy.     

Longevity of protective immunity to experimental bovine herpesvirus-1 infection following inoculation with a combination modified-live virus vaccine in beef calves

OBJECTIVE: To determine whether a combination viral vaccine containing modified-live bovine herpesvirus-1 (BHV-1) would protect calves from infection with a recent field isolate of BHV-1. DESIGN: Randomized controlled trial. ANIMALS: Sixty 4- to 6-month-old beef calves. PROCEDURE: Calves were inoculated with a placebo 42 and 20 days prior to challenge (group 1; n = 10) or with the combination vaccine 42 and 20 days prior to challenge (group 2; 10), 146 and 126 days prior to challenge (group 3; 10), 117 and 96 days prior to challenge (group 4; 10), 86 and 65 days prior to challenge (group 5; 10), or 126 days prior to challenge (group 6; 10). All calves were challenged with BHV-1 via aerosol. Clinical signs, immune responses, and nasal shedding of virus were monitored for 14 days after challenge. RESULTS: Vaccination elicited increases in BHV-1-specific IgG antibody titers. Challenge with BHV-1 resulted in mild respiratory tract disease in all groups, but vaccinated calves had less severe signs of clinical disease. Extent and duration of nasal BHV-1 shedding following challenge was significantly lower in vaccinated calves than in control calves. In calves that received 2 doses of the vaccine, the degree of protection varied with the interval between the last vaccination and challenge, as evidenced by increases in risk of clinical signs and extent and duration of viral shedding. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that this combination vaccine provided protection from infection with virulent BHV-1 and significantly reduced nasal shedding of the virus for at least 126 days after vaccination.     

Evaluation of inactivated infectious bovine rhinotracheitis vaccines.

Sixty-five calves of approximately three months of age and of mixed sex were vaccinated twice at four week intervals with either attenuated or inactivated infectious bovine rhinotracheitis vaccines. Following initial vaccination there was no demonstrable serum infectious bovine rhinotracheitis titer in any of the calves receiving the inactivated vaccine with 20.7% of the calves receiving the attenuated vaccines having demonstrable titers. Following a second administration of vaccine at eight weeks post-initial vaccination 63.9% of the calves receiving the inactivated vaccine had no demonstrable titer with 72.4% of the calves receiving the attenuated vaccine exhibiting a blood titer of four or greater.     

Investigation of possible vaccine-induced epizootics of infectious bovine rhinotracheitis, using restriction endonuclease analysis of viral DNA

Viral DNA was extracted from each of 14 modified-live (ML) bovine herpesvirus 1 vaccines, representing all of the ML infectious bovine rhinotracheitis virus (IBRV) vaccines licensed by the US Department of Agriculture for use in cattle. Restriction endonucleases Pst I and Bgl II were used to establish restriction enzyme patterns for the vaccinal viruses. Viral DNA from isolates obtained from 6 field samples of IBRV (1 from Colorado, 1 from West Virginia, 3 from Wisconsin, 1 from South Dakota) were digested with restriction endonucleases, and patterns were compared to evaluate the role of vaccinal virus in these field epizootics of infectious bovine rhinotracheitis. Animals from which field samples were obtained had been vaccinated with ML IBRV vaccine before the epizootic of infectious bovine rhinotracheitis occurred in the herds. In 2 of the 6 field samples, DNA restriction endonuclease analyses patterns from the isolates were indistinguishable from the pattern for the vaccinal viruses used. In the remaining 4 field samples, DNA restriction endonuclease analyses patterns of the IBRV from isolates were different from those of the vaccinal viruses.     

Evaluation of protection against virulent bovine viral diarrhea virus type 2 in calves that had maternal antibodies and were vaccinated with a modified-live vaccine

OBJECTIVE: To evaluate the efficacy of an adjuvanted modified-live bovine viral diarrhea virus (BVDV) vaccine against challenge with a virulent type 2 BVDV strain in calves with or without maternal antibodies against the virus. DESIGN: Challenge study. ANIMALS: 23 crossbred dairy calves. PROCEDURES: Calves were fed colostrum containing antibodies against BVDV or colostrum without anti-BVDV antibodies within 6 hours of birth and again 8 to 12 hours after the first feeding. Calves were vaccinated with a commercial modified-live virus combination vaccine or a sham vaccine at approximately 5 weeks of age and challenged with virulent type 2 BVDV 3.5 months after vaccination. Clinical signs of BVDV infection, development of viremia, and variation in WBC counts were recorded for 14 days after challenge exposure. RESULTS: Calves that received colostrum free of anti-BVDV antibodies and were vaccinated with the sham vaccine developed severe disease (4 of the 7 calves died or were euthanatized). Calves that received colostrum free of anti-BVDV antibodies and were vaccinated and calves that received colostrum with anti-BVDV antibodies and were vaccinated developed only mild or no clinical signs of disease. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the modified-live virus vaccine induced a strong protective immune response in young calves, even when plasma concentrations of maternal antibody were high. In addition, all vaccinated calves were protected against viral shedding, whereas control calves vaccinated with the sham vaccine shed virus for an extended period of time.     

The serological response to foot-and-mouth disease vaccination is not affected by simultaneous infectious bovine rhinotracheitis/adenovirus/parainfluenza 3 vaccination

Young calves were simultaneously vaccinated by subcutaneous route against foot-and-mouth disease (FMD) and against infectious bovine rhinotracheitis/adenovirus/parainfluenza-3 (IBR/Adeno/PI-3) by intranasal route. The serological response against the 3 FMD virus types of the FMD vaccine was clearly positive. There was no significant difference between results of simultaneous FMD and IBR/Adeno/PI-3 vaccination and FMD vaccination only.     

A bovine respiratory virus vaccination trial

A respiratory virus vaccination trial was carried out in a commercial calf-rearing unit with a history of virus pneumonia. The effects of vaccination on the incidence of virus respiratory disease and growth rate were assessed. Forty-four bought-in calves were allocated to groups and treated as follows: A, unvaccinated controls; B, intranasal temperature-sensitive infectious bovine rhinotracheitis (IBR) vaccine at three and 10 weeks; C, intranasal temperature-sensitive combined IBR and parainfluenza-3 (PI3) vaccine at three and 10 weeks; D, intranasal temperature-sensitive combined IBR and PI3 vaccine at three and 10 weeks plus live attenuated bovine respiratory syncytial (BRS) virus vaccine intramuscularly at seven, 10 and 16 weeks. Two outbreaks of virus pneumonia occurred, one at three to four months of age associated with BRS virus and the other at four to five months of age with PI3 virus. During these outbreaks the incidence of pneumonia was lower and the number of days of elevated temperature and the number of treatments were significantly less in groups vaccinated against the associated virus. Despite these findings there were no significant differences between the growth rates of the groups either during the outbreaks of virus pneumonia or during the 10 month period to slaughter.