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.     

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.     

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.     

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.     

Q fever (Coxiella burnetii) investigations in dairy cattle: challenge of immunity after vaccination

The immunity of Holstein-Friesian dairy cows vaccinated against Coxiella burnetii was challenged with 4 X 10(8) infective guinea pig doses of viable rickettsiae. Cows that were vaccinated had normal full-term calves, whereas 2 nonvaccinated cows aborted late in pregnancy. Intrauterine infection of the fetus was indicated by recovery of the organism from tissues of the fetus. Coxiella burnetii was recovered from milk, colostrum, and placenta of vaccinated and nonvaccinated cows after challenge inoculation, but the rickettsiae recovered were as many as 1,000 times more numerous in nonvacinated cows.     

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.     

Experiences with a vaccine being developed for the control of swine dysentery

A prototype vaccine that is being developed for the control of swine dysentery (SD) was tested in two groups of experimental pigs. Vaccination induced high circulating antibody titres against the aetiological agent, Serpulina (Treponema) hyodysenteriae. Pigs in the first trial were vaccinated twice before being challenged orally with the bacteria. Five of 6 unvaccinated animals developed dysentery within a fortnight of challenge, but only 1 of 6 vaccinated pigs showed signs of disease at this time. Unexpectedly, 1 mo after challenge, the surviving unvaccinated pig and 2 remaining healthy vaccinated animals succumbed to the disease. The reason for the development of this late-onset form of dysentery was not clear. In the second trial, 8 pigs were vaccinated 3 times. Only 2 of these animals (25%) developed severe dysentery after being mixed with infected pigs, whereas 7 of 8 (88%) unvaccinated control pigs in the same pen became diseased. The late-onset form of dysentery was not observed. The prototype vaccine for SD provided a useful level of protection, and could be used in programs to control the disease in Australia.     

Large-scale use of liquid-phase blocking sandwich ELISA for the evaluation of protective immunity against aphthovirus in cattle vaccinated with oil-adjuvanted vaccines in Argentina

Specific serum activity levels against four reference strains of foot-and-mouth disease virus (FMDV) were evaluated from 1634 animals vaccinated with commercial quadrivalent oil vaccines and from 746 unvaccinated, naive animals, using the liquid-phase blocking sandwich ELISA (lpELISA) test. Cows from the FMDV-free area of Argentina were tested for the absence of specific FMDV antibodies (sp FMDV Abs) and those showing lpELISA titres < 1.0 were grouped in lots of 16 animals. They were vaccinated and challenged at 90 days postvaccination (DPV) with one of four virus strains used for vaccine production and control (prototype strains). Serum samples from vaccinated and control cattle were collected 60 and 90 DPV and the level of sp FMDV Abs was determined by lpELISA. Animals were examined for clinical signs of disease. Results show that serum lpELISA titre levels directly correlate with the percentage of protected animals. It was seen that 100, 98, 93 and 87% of the vaccinated cattle with antibody titre levels > or = 2.1 were protected against challenge with serotypes C85, A87,01 Cas and A79, respectively. Evidence is also presented of seroconversion in a sample of 3-5-month-old calves vaccinated in the field, showing lpELISA titres compatible with protection against the four vaccine viruses as long as 150 DPV. Results reported in this paper strongly support the use of the lpELISA test for a rapid and reliable evaluation of the efficacy of FMDV commercial vaccines as well as for the assessment of the immunological status of cattle in FMDV-free and enzootic regions of South America.     

The insulin receptor substrate 1 associates with phosphotyrosine phosphatase SHPTP2 in liver and muscle of rats

OBJECTIVE: To determine efficacy of a vaccine containing modified-live bovine viral diarrhea virus (BVDV) type 1 for protecting pregnant cows and their fetuses against virulent heterologous BVDV type 1. DESIGN: Randomized controlled cohort study. ANIMALS: 18 yearling beef heifers seronegative for BVDV and negative when tested for BVDV by virus isolation. PROCEDURE: Cattle were randomly assigned to control (unvaccinated; n = 6) or vaccinated (12) groups. Vaccinated heifers were given a combination vaccine containing modified-live BVDV type 1 comprising a cytopathic (NADL) strain. All 18 heifers were then bred and challenge-exposed between 70 and 75 days of gestation with BVDV type 1, administered intranasally. Cattle were monitored, and infection status of offspring was determined after parturition. Antibody concentrations of vaccinated and control heifers were also monitored. RESULTS: All 6 calves from control heifers had positive results on multiple virus isolation tests and were considered persistently infected. In comparison, only 2 calves from vaccinated cows had positive results on virus isolation tests and were considered persistently infected. One vaccinated heifer aborted, but the fetus was not persistently infected, and the abortion was not attributed to BVDV infection. CLINICAL IMPLICATIONS: Analysis of these data indicated that a single dose of a modified-live NADL-derived BVDV type 1 vaccine will confer protection to dams and their fetuses against challenge-exposure to heterologous BVDV type 1 organisms.     

Glycoprotein E2 of bovine viral diarrhea virus expressed in insect cells provides calves limited protection from systemic infection and disease

Calves were vaccinated with a C-terminally truncated baculovirus expression product of E2 from the Singer strain of bovine viral diarrhea virus. The expressed E2 was glycosylated and retained antigenic authenticity. After induction of viral neutralizing antibody, the calves were challenge exposed with either the homologous Singer strain of virus or with the heterologous 890 strain of virus. Vaccine-induced antibody titer of > or = 2 protected calves from clinical signs of disease induced by homologous viral challenge exposure. An antibody titer of > or = 512 reduced replication of homologous challenge virus to a level which did not induce an appreciable increase in serologic titer of viral neutralizing antibody. Vaccine-induced antibody titer of < or = 4096 did not protect calves from systemic spread of virus or from disease after challenge exposure with heterologous bovine viral diarrhea virus.     

Attitudes of oncologists, family doctors, medical students and lawyers to euthanasia

OBJECTIVE: To evaluate clearance of the vaccine strain, immunologic responses, and potential shedding of Brucella abortus strain RB51 organisms after vaccination of bison calves. ANIMALS: Fourteen 7-month-old female bison calves. PROCEDURE: 10 bison calves were vaccinated SC with 1.22 x 10(10) colony-forming units of B abortus strain RB51. Four bison calves were vaccinated SC with 0.15M NaCl solution. Rectal, vaginal, nasal, and ocular swab specimens were obtained to evaluate potential shedding by vaccinated bison. The superficial cervical lymph node was biopsied to evaluate clearance of the vaccine strain. Lymphocyte proliferative responses to strain RB51 bacteria were evaluated in lymph node cells obtained from biopsy specimens and also in peripheral blood mononuclear cells. RESULTS: Strain RB51 was recovered from superficial cervical lymph nodes of vaccinates examined 6, 12, and 18 weeks after vaccination (4/4, 3/4, and 1/4, respectively) but not in vaccinates examined at 24 weeks (0/3) after vaccination or nonvaccinates examined at all sample collection times (n = 1 bison/sample period). Serologic, immunologic, and bacterial culture techniques failed to reveal shedding of strain RB51 by vaccinates or infection of nonvaccinated bison. Lymphocyte proliferative responses were evident in lymph node cells and blood mononuclear cells from strain RB51-vaccinated bison beginning 12 weeks after vaccination. CONCLUSION: Strain RB51 was cleared from bison by 18 to 24 weeks after vaccination. Bison vaccinated with strain RB51 did not shed the vaccine strain to nonvaccinated bison housed in close proximity. Strain RB51 did not induce antibody responses in bison that would interfere with brucellosis surveillance tests, but did stimulate cell-mediated immunity.     

Efficacy of intratracheal administration of Newcastle disease vaccine in day-old chicks

Groups of day-old chicks with varying levels of parental antibody were vaccinated against Newcastle disease (B1 strain) with a commercially available device which simultaneously debeaks the chick and emits a fine spray of vaccine into its trachea. Some groups were also vaccinated (B1 or Lasota strain) with a commercially available vaccine sprayer at 9 days, 14 days, or 9 and 25 days of age. Response to vaccine was evaluated once each week during the experimental period of approximately 8 weeks HI titers were determined and 10 chicks were challenged with the Texas GB strain of Newcastle disease virus. In chicks with low to moderate levels of maternal antibody a satisfactory antibody response was attained by vaccination at 1 day of age, and in most cases resistance to challenge was evident by 3 weeks of age. Intratracheal vaccination of chicks with extremely high levels of maternal antibody had a minimal antibody response. All groups of chicks spray vaccinated at 9, 14, or 9 and 25 days of age showed a marked increase in antibody titer regardless of whether they had been vaccinated at 1 day of age.     

Vaccine protection by a triple deletion mutant of simian immunodeficiency virus

Twelve rhesus monkeys were vaccinated with SIVmac316 delta nef (lacking nef sequences), and 12 were vaccinated with SIVmac239 delta3 (lacking nef, vpr, and upstream sequences in U3). SIVmac316 and SIVmac239 differ by only eight amino acids in the envelope; these changes render SIVmac316 highly competent for replication in macrophages. Seventeen of the animals developed persistent infections with the vaccine viruses. Seven of the 24 vaccinated animals, however, developed infections that were apparently transient in nature. Six of these seven yielded virus from peripheral blood when tested at weeks 2 and/or 3, three of the seven had transient antibody responses, but none of the seven had persisting antibody responses. The 24 monkeys were challenged in groups of four with 10 rhesus monkey infectious doses of wild-type, pathogenic SIVmac251 at weeks 8, 20, and 79 following receipt of vaccine. None of the seven with apparently transient infections with vaccine virus were protected upon subsequent challenge. Analysis of cell-associated viral loads, CD4+ cell counts, and viral gene sequences present in peripheral blood in the remainder of the monkeys following challenge allowed a number of conclusions. (i) There was a trend toward increased protection with length of time of vaccination. (ii) Solid vaccine protection was achieved by 79 weeks with the highly attenuated SIV239 delta3. (iii) Solid long-term protection was achieved in at least two animals in the absence of complete sterilizing immunity. (iv) Genetic backbone appeared to influence protective capacity; animals vaccinated with SIV239 delta3 were better protected than animals receiving SIV316 delta nef. This better protection correlated with increased levels of the replicating vaccine strain. (v) The titer of virus-neutralizing activity in serum on the day of challenge correlated with protection when measured against a primary stock of SIVmac251 but not when measured against a laboratory-passaged stock. The level of binding antibodies to whole virus by enzyme-linked immunosorbent assay also correlated with protection.     

Metabolism of the carcinogen N-hydroxy-N-2-fluorenylacetamide by rat peritoneal neutrophils

A thymidine kinase (TK), inverted repeat, glycoprotein I (gI) and glycoprotein X (gpX) gene-deleted modified live virus pseudorabies vaccine was evaluated for safety in swine and for efficacy in protecting swine against challenge with pseudorabies virus (PRV). Safety was evaluated by inoculating pregnant gilts intravenously and 3-day-old pigs intracerebrally with the vaccine. Efficacy was evaluated by 1) vaccinating 3-day-old pigs with a minimal protective dose intranasally and then challenging with PRV 3 weeks postvaccination or 2) vaccinating weaned pigs with a standard field dose intramuscularly and then challenging with PRV 4 weeks postvaccination. The pigs vaccinated intranasally remained clinically normal following vaccination and challenge with PRV. The pigs vaccinated intramuscularly remained clinically normal following vaccination, but mild respiratory signs were seen in some of the vaccinated pigs following challenge with PRV. Humoral immune response was evaluated with enzyme-linked immunosorbent assays (ELISAs) and a serum virus neutralization test. All of the intramuscularly vaccinated pigs became gI and gpX positive on differential ELISAs following challenge. All of the intranasally vaccinated pigs were seropositive on the indirect gI ELISA following challenge, but not all of the pigs were seropositive on the blocking gI ELISA or the gpX ELISA 3 weeks postchallenge.     

Use of a live chlamydial vaccine to prevent ovine enzootic abortion

A lyophilised chlamydial vaccine was prepared from the 1B temperature-sensitive strain of ovine Chlamydia psittaci. Ewes inoculated with a low titre of the live vaccine four weeks before artificial insemination were challenged on day 70 of gestation with five UK field isolates of C psittaci, including strains A22 and S26/3 previously incorporated into a commercial inactivated vaccine. There was a significantly lower chlamydial abortion rate after challenge in the vaccinated group (7.1 per cent) than in the unvaccinated group (80 per cent). All the lambs born to the vaccinated ewes were viable and of good quality. The vaccine also reduced the number of infected ewes in the group and the severity of the infection. The compatibility of the chlamydial vaccine and a toxoplasma vaccine was also tested. The abortion rate of ewes vaccinated with the two vaccines at separate injection sites (16 per cent) was less than that of ewes vaccinated with both vaccines at one site (32 per cent).     

Clinical study on air in epidural hematomas

Twenty 2nd specific pathogen-free pigs were divided into 4 groups: Group A were infected with porcine reproductive and respiratory syndrome (PRRS) virus at 6 weeks of age and treated with available swine erysipelas and swine fever combined vaccine (vaccinated) at 7 weeks of age; Group B were vaccinated at 7 weeks of age and infected with PRRS virus at 8 weeks of age; Group C were vaccinated at 7 weeks of age: Group D were neither vaccinated nor infected with PRRS virus. All pigs were challenged to Erysipelothrix rhusiopathiae C42 strain at 10 weeks of age. No clinical signs appeared after vaccination of group A and B pigs, thus confirming that the safety of the vaccine was not influenced by infection with PRRS virus. None of the pigs in Groups A and C developed erysipelas after challenge exposure to E. rhusiopathiae. In contrast, fever and/or urticaria appeared transiently in all pigs of Group B after challenge exposure. At the time of challenge exposure to E. rhusiopathiae, the PRRS virus titer was high in sera of Group B, but was low in those from Group A. However, vaccination of pigs with attenuated E. rhusiopathiae was effective in dual infection with PRRS virus and E. rhusiopathiae, because the clinical signs were milder and the E. rhusiopathiae strain was less recovered from these pigs compared to pigs of group D.     

Effects of the sucking louse (Linognathus vituli) on the grooming behaviour of housed calves

The behaviour of cattle with and without louse infestation was studied for eight weeks. Thirty-two crossbred calves were housed in groups of four at 20 weeks old. Sixteen of the calves were artificially infested with the long-nosed cattle louse Linognathus vituli and 16 were left uninfested as controls. In infested animals the number of lice on the shoulders averaged 2.3 per 10 cm length of parted hair. The recorded frequency of irritation, manifested by rubbing and self-licking, was significantly greater in the louse-infested calves than in the uninfested controls. The infested calves spent 28 s/h rubbing and 95 s/h self-licking, compared with 8 s and 62 s/h spent by the uninfested controls. The infested calves also spent more than twice as long scratching as the controls. There were no significant effects of the infestation on social grooming.     

Virulence, immunogenicity and reactivation of bovine herpesvirus 1 mutants with a deletion in the gC, gG, gI, gE, or in both the gI and gE gene

Within the framework of developing a marker vaccine against bovine herpesvirus 1 (BHV1), several mutants with deletions in non-essential glycoprotein genes were constructed. Glycoprotein gC, gG, gI and gE single deletion mutants, a gI/gE double deletion mutant and a gE frame-shift mutant were made. The virulence and immunogenicity of these mutants were evaluated in specific-pathogen-free calves. Except for the gC deletion mutant, all mutants were significantly less virulent than the parental wild-type (wt) BHV1 strain Lam. The virulence of the gI and the gI-/gE- mutants was almost completely reduced. Upon challenge infection, the calves of the control group became severely ill, whereas all other calves remained healthy. The reduction of the virus shedding after challenge infection was related to the virulence of the strain of primary inoculation. Virus shedding was almost completely reduced in calves first inoculated with Lam-wt or with gC- and the least reduced in calves inoculated with gI- or gI-/gE-. Six weeks after challenge, all calves were treated with dexamethasone to study whether mutant or challenge virus or both could be reactivated. The gC- and the gG- mutants were reactivated, whereas none of the other mutants were reisolated. Reactivation of challenge virus was reduced in all calves inoculated with mutant viruses. The gC deletion mutant was too virulent and the gI and the gI/gE deletion mutants were the least immunogenic, but based on residual virulence and immunogenicity, both the gG and the gE deletion mutants are candidates for incorporation in live BHV1 vaccines. However, it also depends on the kinetics of the anti-gG and anti-gE antibody response after wild-type virus infection, whether these deletion mutants are really suitable to be incorporated in a marker vaccine.     

Development of effective living vaccines against bovine babesiosis--the longest field trial?

Between 1959 and 1996, research was performed to change a vaccine against babesiosis in Australia and to improve it as actual or threatened untoward field responses became apparent. The most significant change occurred in 1964 with the traditionally used carriers of Babesia being replaced as vaccine donors by acutely infected splenectomised calves. This ensured the infectivity of the vaccine and was fortuitously associated with a reduction in the virulence of Babesia bovis in vaccine. Since then, more than 27 million doses of highly infective vaccine have been supplied from the laboratory at Wacol near Brisbane. This vaccine reduced serious losses from babesiosis in vaccinated cattle in Australia to very low levels and has now gained acceptance worldwide. Research to ensure the continuing effectiveness of the vaccine has proved to be essential.     

Effect on viraemia of an American and a European serotype PRRSV vaccine after challenge with European wild-type strains of the virus

Three groups of 10 pigs were vaccinated with an American serotype porcine reproductive and respiratory syndrome virus (PRRSV) vaccine and three groups of 10 pigs were vaccinated with a European serotype PRRSV vaccine. A control group of 12 pigs was left unvaccinated. Four weeks after vaccination the PRRSV-specific antibody titres were determined and each group was challenged with either a Spanish, German or Dutch PRRSV wild-type strain. The serological responses four weeks after vaccination confirmed that the two vaccines were of different serotypes. Vaccination with the American serotype vaccine hardly reduced the level of viraemia after challenge with the European PRRSV wild-type strains, and only after challenge with the Spanish PRRSV strain was a moderate, statistically significant reduction in viraemia observed. In contrast, after vaccination with the European serotype vaccine, viraemia was completely suppressed after challenge with the German PRRSV isolate and almost completely suppressed after challenge with the Spanish and Dutch PRRSV isolates.