Efficacy of a temperature-sensitive modified-live bovine herpesvirus type-1 vaccine against abortion and stillbirth in pregnant heifers

OBJECTIVE: To evaluate the efficacy of a commercially available temperature-sensitive modified-live bovine herpesvirus type-1 (BHV-1) vaccine against BHV-1 challenge-induced abortion and stillbirth. DESIGN: Prospective randomized control trial. ANIMALS: 20 cycling, nonpregnant, BHV-1 seronegative heifers of various breeds and weights, 12 to 15 months old. PROCEDURE: Heifers were randomly assigned to a vaccinate (n = 10) or nonvaccinate control (n = 10) group. Seventeen to 26 days after members of the vaccinate group received a second dose of vaccine, all heifers were artificially inseminated. Heifers were challenged intravenously with Cooper strain BHV-1 between days 177 and 187 of gestation. Aborted fetuses and stillborn calves were necropsied, and tissues collected for histologic examination and virus isolation. Heifers, calves, and fetuses were tested for BHV-1 antibody throughout the study. RESULTS: The difference in number of abortions or stillbirths between vaccinated heifers (1/10) and control heifers (10/10) was significant (P < 0.003). Seven of 10 control heifers had a virus neutralization antibody titer to BHV-1 at abortion or stillbirth that declined or remained unchanged from their titer at a previous serologic evaluation (7 to 66 days earlier). CLINICAL IMPLICATIONS: Prebreeding vaccination of replacement heifers with modified-live BHV-1 vaccine provides fetal protection at 6 months of gestation (7 months after vaccination) and appears to be a reasonable precaution to control economic losses associated with BHV-1 infection. Abortions induced by BHV-1 are not necessarily associated with rising or markedly high virus neutralization antibody titers. These titers should be used cautiously when assessing the role of BHV-1 in bovine abortion and stillbirth.     

A long term epidemiological study of bovine viral diarrhoea infections in a large herd of dairy cattle

Epidemiological aspects of bovine viral diarrhoea virus (BVDV) infections were studied longitudinally in a large dairy herd for three years. At the start of the study, practically all the cows more than four years old had BVDV antibody titres, whereas the younger stock were almost all seronegative. The spread of the virus was monitored in a part of the population that contained only transiently viraemic cattle and in another part that contained persistently viraemic calves. Among the lactating cows the virus circulated for two-and-a-half years, although they had no direct contact with persistently viraemic cattle during this period. The highest transmission rate occurred when a large number of susceptible heifers was added to the population of cows that contained transiently viraemic cattle. The circulation of BVDV among the lactating cows ceased while 27 seronegative cows were still present. Both findings are in accordance with predictions from simple epidemic models. The susceptibility of the cows that remained seronegative was confirmed experimentally. In contrast with the limited circulation of BVDV caused by transiently viraemic cattle, virtually all susceptible cattle that came into contact with a persistently viraemic calf became seropositive within three months. Transplacental BVDV infections were not detected in the calves born to cows that had antibodies against the virus due to an infection that had occurred at least four years earlier. Transplacental transmission of BVDV did not occur in most of the pregnant cows that were infected before approximately the 60th day of gestation, but when cows became infected later in gestation the virus virtually always invaded the fetus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical and immunologic responses of vaccinated and unvaccinated calves to infection with a virulent type-II isolate of bovine viral diarrhea virus

OBJECTIVE: To determine efficacy of a modified-live type-I isolate of bovine viral diarrhea virus (BVDV) vaccine in protecting calves from infection with a virulent type-II isolate, and to determine which type of immune response (i.e., humoral or cellular) correlates with protection. DESIGN: Prospective study. ANIMALS: 28 neonatal Holstein and Holstein-cross calves. PROCEDURE: Within 18 hours of birth, calves received maternal colostrum or were fed pooled colostrum. On days 7 to 10 after birth, calves were determined to be seropositive (n = 16) or seronegative (12) for antibodies to BVDV on the basis of ELISA and virus neutralization test results. Seropositive and seronegative 10- to 14-day-old calves were then given a combined vaccine that contained a modified-live type-I isolate of BVDV or a similar vaccine that lacked protection against bovine viral diarrhea. All calves were inoculated intranasally approximately 21 days after vaccination with a virulent type-II isolate of BVDV. Clinical and immunologic variables, including clinical scores, rectal temperatures, results of CBC with lymphocyte subset analysis, antibody responses, and cell-mediated immune responses, were monitored for 14 days after inoculation. RESULTS: Seronegative-unvaccinated calves developed severe disease and required euthanasia. Vaccination of seronegative calves with a modified-live type-I isolate had a disease-sparing effect as did passive transfer of colostral antibodies to BVDV. Clinical scores were not significantly different between seropositive-vaccinated and seropositive-unvaccinated calves after viral inoculation. CLINICAL IMPLICATIONS: A single dose of a modified-live type-I isolate of BVDV vaccine protects young calves from clinical signs of disease associated with type-II isolates.     

Immunopotentiation of bovine respiratory disease virus vaccines by interleukin-1 beta and interleukin-2

Three experiments, using 85 crossbred beef calves, were conducted to evaluate the adjuvanticity of single, multiple, and combined doses of recombinant bovine IL-1 beta (rBoIL-1 beta) and recombinant bovine IL-2 (rBoIL-2), with a modified-live bovine herpesvirus-1/parainfluenza-3 (BHV-1/PI-3) virus vaccine and a killed bovine viral diarrhea (BVD) virus vaccine. Cytokines were administered intramuscularly at vaccination but at different injection sites. All cytokine treatments increased non-major histocompatibility complex (MHC)-restricted cytolytic capability of peripheral blood mononuclear cells (PBMC) against virus-infected target cells and serum neutralizing (SN) antibody titers to BHV-1 and BVD virus. Multiple, consecutive injections of rBoIL-2 generally showed the greatest adjuvant effect, and no additive effect was observed when rBoIL-1 beta and rBoIL-2 were administered together. In a challenge experiment, calves were vaccinated with a modified-live BHV-1/PI-3 vaccine and infected with BHV-1 on Day 21. Cytokine-treated calves had higher SN antibody titers to BHV-1 than did the control calves at the time of challenge. Calves that were administered rBoIL-2 on 5 consecutive days shed less BHV-1 and had the highest SN antibody titer to BHV-1 (Day 28). These data suggest that rBoIL-1 beta and rBoIL-2 may be useful immunoadjuvants for bovine respiratory disease virus vaccines.     

Congenital abnormalities in newborn calves after inoculation of pregnant cows with Akabane virus

A fresh isolate of Akabane virus was inoculated intravenously into 11 seronegative pregnant cows at 62 to 96 days of gestation. Two of the cows were slaughtered 18 days post-inoculation, and the fetuses were examined; the remaining cows were allowed to give birth. All the inoculated cows developed viremia and neutralizing antibody for the virus, indicating that the cows were actually infected with the virus, although fever or any other clinical abnormalities were not noted. The virus further infected the fetuses. This was proved by virus isolation in one of the two fetuses from the slaughtered cows, and polymyositis was noted in both fetuses. Six of seven calves born alive had anti-Akabane antibody in their precolostral sera, indicating that in utero infection with the virus took place in these calves. Some of the in utero-infected calves demonstrated congenital abnormalities such as cerebral defect, hydranencephaly, and arthrogryposis. These findings provide additional evidence that Akabane virus is the etiological agent of epizootic abortion and congenital arthrogryposis-hydranencephaly syndrome in cattle.     

Milk production and reproductive performance in dairy cows given bovine respiratory syncytial virus vaccine prior to parturition

OBJECTIVE: To assess the effect of vaccination against bovine respiratory syncytial virus on milk production, reproductive performance, and health in lactating dairy cows. DESIGN: Prospective randomized block design. ANIMALS: 385 Holstein dairy cows and heifers. PROCEDURE: Cows were grouped by lactation number, season of calving, and previous mature equivalent 305-day milk production (where appropriate). Prior to parturition, cows and heifers were randomly assigned to be vaccinated i.m. against infectious bovine rhinotracheitis, bovine viral diarrhea, and parainfluenza 3 viruses by use of a three-way vaccine, or to be vaccinated against those viruses as well as bovine respiratory syncytial virus, using a four-way vaccine. Milk production was measured daily through 305 days of lactation. Reproductive and medical records were reviewed to obtain insemination dates and record medical problems of cows in each vaccine treatment group. RESULTS: Compared with the three-way vaccine, administration of the four-way vaccine was associated with higher milk production (1.39 kg [3.06 lb] more milk/d) in first-parity cows during the first 21 weeks of lactation. Vaccination did not have any effect on milk production after the first 21 weeks of lactation in cows of any parity. Conception rates at first insemination were higher for four-way vaccinated first-parity cows than for three-way vaccinated first-parity cows (54.6 vs 32.7%). Compared with second-parity cows that received the three-way vaccine, first insemination conception rate was improved for second-parity cows vaccinated with the four-way vaccine (28.9 vs 47.8%, respectively). In cows of third or greater parity, first insemination conception rate was not different between the 2 vaccine treatment groups. CLINICAL IMPLICATIONS: Vaccination of heifers against bovine respiratory syncytial virus prior to partrition may increase milk production and first insemination conception rates.     

Stimulus specific adaptation in inferior temporal and medial temporal cortex of the monkey

We studied the early immunity induced by a live glycoprotein E (gE) negative bovine herpesvirus 1 (BHV1) marker vaccine. Three groups of specific-pathogen-free calves were either not vaccinated, or vaccinated two days or two hours before the introduction of a calf that was intranasally infected with wild-type BHV1 the day before. We quantified the shedding of gE-negative vaccine virus and of wild-type virus, using a double-staining immunoassay. In calves vaccinated two hours before the introduction of the infected calf, the shedding of wild-type virus was reduced, compared with that of the unvaccinated control calves. The shedding of wild-type virus was most significantly reduced in the calves that were vaccinated two days before: only very small amounts of wild-type virus were isolated. Wild-type virus was not detected at all in the samples from one of the five calves of that group. Furthermore, this calf was the only one in which we did not detect antibodies against gE. Hence, intranasal vaccination with a live gE-negative vaccine induced early immunity against a BHV1 contact infection. This suggests that this vaccine can be used efficaciously in the early stages of a BHV1 outbreak.     

Delirium and persistent dyskinesia induced by a lithium-neuroleptic interaction

Vaccination with live cytopathogenic (cp) bovine viral diarrhoea virus (BVDV) is often used for control of this disease. In animals which are persistently infected with noncytopathogenic (ncp) BVDV this can lead to the outbreak of mucosal disease (MD). To simulate vaccination of such animals and to monitor the clinical-virological course after superinfection, nine clinically healthy calves which were persistently viremic were superinfected with different cp BVDV strains. One animal succumbed to early onset MD within three weeks after superinfection. During the observation period of 18 months four animals developed severe clinical signs. While two animals developed late onset MD, the other two had to be euthanized due to clinical signs which could not be related to the superinfecting BVDV. These results indicated that after superinfection or vaccination of persistently infected calves with cp BVDV the probability of developing early and/or late onset MD is significantly increased. The risks arising from uncritical vaccination of herds with unknown virological status in relation with the control of BVDV conforming to the actual official guidelines are discussed.     

Detection of serum antibody responses in cattle with natural or experimental Neospora infections

Parasite-specific antibody responses were detected using an indirect fluorescent antibody (IFA) test in cattle that were naturally or experimentally infected with Neospora parasites. The test was developed using Neospora tachyzoites isolated from an aborted bovine fetus and grown in bovine cell cultures (isolate BPA1). In all cases, infections were confirmed by the identification of Neospora tachyzoites and/or bradyzoite cysts in fetal or calf tissues using an immunoperoxidase test procedure. Fifty-five naturally infected cows that aborted Neospora-infected fetuses had titers of 320-5,120 at the time of abortion. The titer of 6 cows that were serologically monitored over a prolonged period decreased to 160-640 within 150 days after they aborted infected fetuses. Two of the cows showed an increase in their Neospora titers during their subsequent pregnancy, and they gave birth to congenitally infected calves that had precolostral titers of 10,240-20,480. Postcolostral titers of these calves and of 4 other calves with congenital Neospora infections were all > or = 5,120, whereas calves with no detectable parasites had titers < or = 160. Two pregnant heifers that were experimentally infected with the BPA1 isolate at approximately 120 days gestation seroconverted to Neospora antigens within 9 days and developed peak titers of 5,120 and 20,480 within 32 days of infection. The fetus taken by caesarean section 32 days postinfection from 1 heifer and the full-term calf born to the other had Neospora titers of 640 and 10,240, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunohistochemical diagnosis of pestivirus infection associated with bovine and ovine abortion and perinatal death

OBJECTIVE: To establish a reliable, rapid, economical method for detection of pestivirus infection in bovine and ovine fetuses and to examine participation of these viruses in abortions and neonatal mortality. ANIMALS: 213 bovine and 31 ovine fetuses, as well as 36 newborn calves and 25 lambs, which had died within 3 days after birth, were tested for bovine viral diarrhea virus (BVDV) and border disease virus by use of different methods. PROCEDURE: Detection of BVDV in fetuses was performed by immunohistochemical methods, using a panel of monoclonal antibodies against pestivirus antigens on cryostat and paraffin sections and by virus isolation in cell culture; in some instances, an antigencapture ELISA was performed. Results of the various methods were compared. RESULTS: Sensitivity of BVDV detection by immunohistochemical methods and virus isolation in cell culture was equal; however, it decreased in association with autolysis. In autolytic fetuses, use of formalin-fixed, paraffin-embedded brain sections was the most favorable method. Antigen detection by ELISA was less sensitive. CONCLUSIONS: Immunohistochemical analysis of cryostat sections of brain, skin, thyroid gland, abomasum, and placenta is a rapid, sensitive method for detecting pestiviruses in fetuses. In the presence of advanced autolysis, this method used on formalin-fixed, paraffin-embedded brain sections is recommended over the other described methods.     

The occurrence of BVD virus infections in lower Austrian dairy farms

Bulk tank milk samples from 5,024 dairy herds in Lower Austria were tested by ELISA for antibodies to bovine virus diarrhoea virus (BVDV). Approximately 54 per cent of the herds had a low level of bulk tank antibody unsuspected of recent infection with BVDV. In 512 herds, which had a high level of bulk tank antibody suggestive of recent infection with BVDV, milk samples from 5-10 primiparous cows, respectively were tested by ELISA for antibodies to BVDV. In 287 (56.1%) of these 512 herds only antibody-negative primiparous cows were detected. In 759 herds blood samples from 8-10 young stock, respectively were tested by ELISA for antibodies to BVDV. The majority of the tested animals was seronegative in 583 (76.8%) herds. The whole stock from 154 herds was tested for persistent BVDV infections. From 51 herds in all 149 cattle persistently infected with BVDV were detected. Because of the low prevalence of BVDV infections it seems possible to control BVDV without vaccination in Lower Austrian dairy farms.     

A bovine model of vaccine enhanced respiratory syncytial virus pathophysiology

A critical issue has been the observation that vaccination of children with a formalin-inactivated respiratory syncytial virus (RSV) vaccine is associated with disease enhancement. We have taken advantage of bovine RSV and our experience with this disease in calves to develop a natural model that parallels human disease. Using formalin-inactivated bovine RSV vaccine calves were either sham-vaccinated/infected, vaccinated/infected, or vaccinated/sham-infected and their clinical signs, pulmonary function, and histological lung lesions quantitatively scored. Interestingly there was significantly greater disease in vaccinated/infected calves and histological lesions in calves were similar to those of affected children. Finally, we note that vaccination did not induce neutralizing antibodies, but IgG antibodies were detected by ELISA. Our model of RSV enhanced disease is important because it provides quantifiable evidence of disease severity that can be applied to evaluate the mechanisms of immunopathology and the safety of candidate RSV vaccines.     

The dynamics of an infectious disease in a population with birth pulses

In December 1996, a questionnaire about farm management and parasite control measures in calves was sent to 956 randomly chosen dairy cattle farmers in The Netherlands. Another 150 farmers in the vicinity of Deventer who had vaccinated their calves in 1995 against lungworm were approached with the same questions. Our object was to investigate the consequences on worm control of the withdrawal of the lungworm vaccine from the market for reasons of possible BSE contamination of the vaccine. OF the returned questionnaires, 411 (43%) of the 'at random' group and 89 (59.3%) of the 'Deventer' group were valid. The most important data with regard to the farms of the 'at random' group (41) were: mean area 31.6 ha, mean number of calves 23, heifers 23 and milking cows 53. Sheep (mean 37) were present on 18.3% of the farms. With regard to management: 74.5% of the farmers turned the calves in their first year onto pasture, 25.5% kept them indoors. The average time on pasture was ca. 5 months. Rational grazing was practise on 81.4% of the farms, on 18.6% calves were set stocked. The first pasture of the calves was mown before turn-out on 72.9% of the farms. On 48.2% of these farms, calves were always moved to mown pastures. With regard to treatments: 33.8% of the farmers vaccinated their calves against lungworm in the years 1993, 1994 and 1995. Despite the withdrawal of the vaccine from the market in 1996, 7.2% of the farmers vaccinated their calves as recommended, with two doses, and 13.1% with a single dose. At turn-out, 41.5% of the farmers gave the calves a preventive anthelmintic treatment. Of these treatments, 66.9% were sustained of pulse release long acting device. During the grazing season, 36.6% of the farmers treated their calves. After housing 50.3% of the farmers gave a treatment. Signs of lungworm infection were noticed on 18.6% of the farms. Of the 'Deventer' group (89 farmers), 96.6% turned the calves out, Of these farmers, 86.0% had used the lungworm vaccine in 1995. In 1996, 52.7% of the farmers had vaccinated the calves:36.5% with a single dose and 16.2% with the double dose. Of the 35 farmers who did not vaccinate in 1996, 62.9% gave a preventive treatment at turn-out. Clinical signs of lungworm infection were not observed on the 12 farms which vaccinated the calves twice. On 11% of the farms which vaccinated once and on 14% of the farms which did not vaccinate, signs of lungworm infection were observed. It is concluded that more than 80% of Dutch dairy cattle farmers take appropriate measures to control gastrointestinal nematode and lungworm infections in calves in their first grazing season by grazing on aftermath, rotational grazing on mown pastures combined or not with preventive anthelmintic treatments. However, combinations of aftermath grazing and preventive treatment occurred on 30% of the farms. This may be overprotective and may prevent sufficient build up of immunity, causing worm problems at a later age. The withdrawal of the lungworm vaccine from the market did not cause a rise in lungworm problems. Some farmers did vaccinate, despite the withdrawal. The majority used other preventive treatment measures, mainly the application of long acting boli.     

Experimental infection with Babesia divergens in cattle persistently infected with bovine virus diarrhoea virus

Nine Norwegian Red cattle, aged 7-14 months, persistently infected with bovine virus diarrhoea virus (BVDV) were inoculated with a Swedish strain of Babesia divergens. Six persistently infected cattle of the same age and breed were kept as controls. Blood and serum samples were collected regularly during the observation period. Rectal temperatures were recorded every morning for 25 days post infection, and the animals were examined clinically on a daily basis. Sera were examined for antibodies to B. divergens by indirect immunofluorescence antibody test (IFAT). Eight of the infected animals developed fever of 2-5 days duration. Babesia divergens organisms appeared in the erythrocytes of all infected animals on the day after inoculation. The parasitaemia lasted for 4-11 days. One animal had a transient haemoglobinuria. Compared with the control group, there was a 20% decrease in the haematocrit. There was a transient lymphopenia and thrombocytopenia during the period of fever. There were no differences in mean numbers of neutrophils between the two persistently infected groups. Compared with cattle free of BVDV, the persistently infected cattle had consistently lower total leucocyte count that was mainly due to decreased mean numbers of neutrophils and monocytes. All infected animals develop antibodies > or = 1:1280 between day 7 and 10 post infection. The magnitude of the antibody response was considerably lower than that of BVDV-free animals inoculated with the same strain and dosage of B.divergens.     

Effect of dual-subtype vaccine against feline immunodeficiency virus infection

Dual-subtype feline immunodeficiency virus (FIV) vaccine, consisting of inactivated cells infected with subtypes A (Petaluma strain) and D (Shizuoka strain), was developed and tested for its vaccine efficacy against FIV infection in specific pathogen free (SPF) cats. Animals were monitored for proviral DNA by FIV-specific PCR and for FIV-specific antibody profiles by ELISA and virus-neutralization assays. In addition, blood from challenged cats was inoculated into naive SPF cats to confirm the viral status of the vaccinated cats. All cats immunized with Petaluma vaccine alone were protected against homologous Petaluma challenge, but only one of four cats was protected against heterologous Shizuoka challenge. More importantly, all cats immunized with the dual-subtype vaccine were protected against both Petaluma and Shizuoka challenges. These results suggest that a multi-subtype vaccine approach may provide the broad-spectrum immunity necessary for vaccine protection against strains from different subtypes.     

An experimental study of a concurrent primary infection with bovine respiratory syncytial virus (BRSV) and bovine viral diarrhoea virus (BVDV) in calves

Experimental infections with bovine respiratory syncytial virus (BRSV) and bovine viral diarrhoea virus (BVDV) were performed to study the effect of concurrent BRSV and BVDV infections. Twelve seronegative calves, in 3 groups, were inoculated on a single occasion with pure BRSV (group A), BRSV and noncytopathogenic BVDV (group B) or mock infected (group C). Mild respiratory symptoms were recorded 4 to 5 days post inoculation (dpi) in group A and group B calves. One calf in group A was severely affected and required medical treatment. In group B, fever (40.7-41.4 degrees C) was prominent 7 to 8 dpi. Only calves in group B were BVDV positive in purified lymphocytes at 2 to 14 dpi and showed increased serum interferon levels, with a peak at 4 dpi, indicating BVDV to be responsible for inducing the rise. BRSV was detected in lung lavage fluids up to 7 dpi for group A calves, compared to 11 dpi for group B and calves in this group also seroconverted later displaying lower BRSV titers. The time lag before an antibody response and the titers recorded in group B, indicated that the duration of BVDV infection in lymphocytes negatively influenced the capacity to mount a BRSV antibody response.     

Effect of genotype on the hormonal activity of the Leydig cells during stress in inbred strains of mice

Paraffin sections from various organs of sheep fetuses following transplacental infection with non-cytopathogenic (ncp) bovine viral diarrhoea virus (BVDV) or cytopathogenic (cp) BVDV were stained immunohistochemically with BVDV-specific monoclonal antibodies. Comparison of the distribution of viral antigen in sections from fetuses of experiment A revealed that in organs such as parotid, thyroid, thymus, lung, spleen, kidney, liver and skin from 20 days post inoculation (p.i.) onwards numerous antigen-containing cells were present. In organs of fetuses infected with cp BVDV, however, antigen-positive cells were only detectable until days 10 and 14 p.i. These findings suggest that the ncp BVDV used in experiment A replicated considerably faster and more efficient than the cp BVDV used in experiment B and that the two virus biotypes differ considerably concerning their tropism for fetal ovine organs.     

Prevalence of antibodies to bovine virus diarrhoea virus and other viruses in bulk tank milk in England and Wales

Bulk tank milk samples from 1070 dairy herds in England and Wales were tested by ELISA for antibodies to bovine virus diarrhoea virus (BVDV). A subset of 341 herds was tested by ELISA for antibodies to bovine herpesvirus 1 (BHV-1), bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCV). None of the herds had less than 40 dairy cows and none had been vaccinated against BVDV. The prevalence of BVDV antibody-positive herds in the national population was estimated at 95 per cent and approximately 65 per cent of the herds had a high level of bulk tank antibody suggestive of recent infection with BVDV. Dairy herds in East Anglia and the south-east of England had a significantly lower risk of being BVDV antibody-positive than herds in the rest of England and Wales. However, these regional differences tended to diminish with increasing herd size. Around 69 per cent of the herds were BHV-1 antibody-positive and all the herds were antibody positive to BRSV and BCV. Comparison with earlier serological surveys revealed that there had been little change in the prevalence and distribution of BVDV antibody-positive herds in England and Wales over the last 20 years, but that there had been an increase in the prevalence of BHV-1 antibody-positive herds.     

Live attenuated simian immunodeficiency virus (SIV)mac in macaques can induce protection against mucosal infection with SIVsm

OBJECTIVE: To investigate whether vaccination of macaques with attenuated simian immunodeficiency virus (SIV)macC8 could induce long-term protective immunity against rectal exposure to SIVsm and intravenous exposure to the more divergent HIV-2. DESIGN AND METHODS: Eight months after vaccination with live attenuated SIVmacC8, four cynomolgus monkeys were challenged with SIVsm intrarectally and another four vaccinated monkeys were challenged with HIV-2 intravenously. Sixteen months after SIVmacC8 vaccination, another two monkeys were challenged with SIVsm across the rectal mucosa. Two vaccinees shown to be protected against SIVsm were rechallenged 8 months after the first challenge. Ten naive animals were used as controls. Serum antigenaemia, virus isolation, antibody responses, cell-mediated immunity and CD4+ and CD8+ T-cell subpopulations were monitored. PCR-based assays were used to distinguish between virus populations. RESULTS: At the time of challenge, eight out of 10 vaccinees were PCR-positive for SIVmacC8 DNA but no virus could be isolated from peripheral blood mononuclear cells. After SIVsm challenge, three out of six vaccinees were repeatedly SIVsm PCR-negative. In one of the three infected monkeys, the challenge virus was initially suppressed but the monkey ultimately developed AIDS after increased replication of the pathogenic virus. Rechallenged monkeys remained protected. All HIV-2-challenged vaccinees became superinfected. All controls became infected with either SIVsm or HIV-2. At the time of challenge the vaccinees had neutralizing antibodies to SIVmac but no demonstrable cross-neutralizing antibodies to SIVsm or HIV-2. Titres of antigen-binding or neutralizing antibodies did not correlate with protection. Cytotoxic T-cell responses to SIV Gag/Pol and virus-specific T-cell proliferative responses were low. CONCLUSION: The live attenuated SIVmacC8 vaccine was able to induce long-term protection against heterologous intrarectal SIVsm challenge in a proportion of macaques but not against the more divergent HIV-2, which was given intravenously.     

Immunization of cattle with a BHV1 vector vaccine or a DNA vaccine both coding for the G protein of BRSV

A gE-negative bovine herpesvirus 1 (BHV1) vector vaccine carrying a gene coding for the G protein of bovine respiratory syncytial virus (BRSV) (BHV1/BRSV-G) induced the same high degree of protection in calves against BRSV infection and BHV1 infection as a multivalent commercial vaccine. A DNA plasmid vaccine, carrying the same gene as the BHV1/BRSV-G vaccine, significantly reduced BRSV shedding after BRSV infection compared with that in control calves, but less well than the BHV1/BRSV-G vaccine. Flow cytometric analysis showed a significant relative increase of gamma/delta+ T cells in peripheral blood after BRSV challenge-infection of the calves of the control group but not in the vaccinated groups. These results indicate that the G protein of BRSV can induce significant protection against BRSV infection in cattle, and that the BHV1/BRSV-G vaccine protects effectively against a subsequent BRSV and BHV1 infection.