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Papers by Birgit Makoschey

Acta Vet Hung, 2008

The efficacy of an inactivated bovine respiratory syncytial virus (BRSV)--bovine parainfluenza ty... more The efficacy of an inactivated bovine respiratory syncytial virus (BRSV)--bovine parainfluenza type 3 (PI3)--Mannheimia haemolytica (Mh) combination vaccine was examined in two field studies. Calves were vaccinated (i) with the inactivated vaccine, (ii) a modified live/killed viral combination vaccine, or (iii) left unvaccinated. The efficacy of the vaccines was judged by the (i) number of treated animals, (ii) number of individual antibiotic treatments per calf and (iii) mortality rates. After vaccination with the inactivated vaccine, the number of calves requiring antibiotic treatment was significantly lower than in the unvaccinated group (odds ratios: 0.26 first study and 0.53 second study), but differences between vaccination with live/killed combination vaccines and controls were not significant (odds ratios: 0.56 and 0.90, respectively). In both studies, a number of unvaccinated controls died due to respiratory disease (4.6% first and 6.7% second study). By contrast, none of the animals vaccinated with the inactivated vaccine died in the first study and only 3.3% in the second study. The mortality rates for the groups vaccinated with the live vaccine (1.3% and 7.8%) were similar to the unvaccinated controls. In summary, these data demonstrate the efficacy of the inactivated vaccine under field conditions.

PLOS Neglected Tropical Diseases, 2016

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that affects domesticated ruminants a... more Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that affects domesticated ruminants and occasionally humans. Classical RVF vaccines are based on formalin-inactivated virus or the live-attenuated Smithburn strain. The inactivated vaccine is highly safe but requires multiple administrations and yearly re-vaccinations. Although the Smithburn vaccine provides solid protection after a single vaccination, this vaccine is not safe for pregnant animals. An alternative live-attenuated vaccine, named Clone 13, carries a large natural deletion in the NSs gene which encodes the major virulence factor of the virus. The Clone 13 vaccine was previously shown to be safe for young lambs and calves. Moreover, a study in pregnant ewes suggested that the vaccine could also be applied safely during gestation. To anticipate on a possible future incursion of RVFV in Europe, we have evaluated the safety of Clone 13 for young lambs and pregnant ewes. In line with the guidelines from the World Organisation for Animal health (Office International des Epizooties, OIE) and regulations of the European Pharmacopeia (EP), these studies were performed with an overdose. Our studies with lambs showed that Clone 13 dissemination within vaccinated animals is very limited. Moreover, the Clone 13 vaccine virus was not shed nor spread to in-contact sentinels and did not revert to virulence upon animal-to-animal passage. Importantly, a large experiment with pregnant ewes demonstrated that the Clone 13 virus is able to spread to the fetus, resulting in malformations and stillbirths. Altogether, our results suggest that Clone 13 can be applied safely in lambs, but that caution should be taken when Clone 13 is used in pregnant animals, particularly during the first trimester of gestation.

Berliner und Münchener tierärztliche Wochenschrift

It should be established, whether animals vaccinated intramuscularly (IM) with a live Bovine herp... more It should be established, whether animals vaccinated intramuscularly (IM) with a live Bovine herpesvirus type 1 (BHV-1) marker vaccine become viremic and/or excrete vaccine virus with nasal discharge. Five cattle, seronegative for BHV-1, were vaccinated with an overdose of the vaccine (Bovilis IBR marker live) via the IM route. Nasal swabs and blood samples were taken at regular intervals and tested for BHV-1 in a virus infectivity assay. In addition, a polymerase chain reaction (PCR) specific for BHV-1 DNA was performed on the blood samples. BHV-1 neutralizing antibody titres were determined in the sera taken prior to the vaccination and four weeks after immunisation. AIl animals were successfully vaccinated as judged by the development of BHV-1 neutralising antibodies. However, all nasal swab samples were tested negative for vaccine virus, and all blood samples were found negative for BHV-1 vaccine virus and BHV-1 specific DNA. From these data it can be concluded that the vaccine ...

Vaccine, 2003

Cytokines play a key role as regulators of the immune response. To elucidate whether the efficacy... more Cytokines play a key role as regulators of the immune response. To elucidate whether the efficacy of a live virus vaccine can be improved by co-expression of cytokines, expression cassettes for bovine interleukins (boIL)-2, -4, -6, and -12 and bovine interferon-gamma (boIFN-␥) were integrated into the glycoprotein E (gE)-locus of the bovine herpesvirus 1 (BHV-1) vaccine virus strain GK/D. Cell culture analyses demonstrated that expression of the cytokines did not impair the replication of the recombinant viruses. To test safety and efficacy, groups of 4-6 months old BHV-1 seronegative calves were vaccinated intranasally with the parental virus strain GK/D or the recombinants, and challenged intranasally 3 weeks later with virulent BHV-1. The animals were monitored for clinical signs, virus excretion and antibody status after vaccination and challenge. All vaccines were well tolerated and protected the immunised calves from clinical disease following challenge, and reduced duration and titres of challenge virus shedding. Calves inoculated with the boIL-6, boIL-12 and boIFN-␥ expressing recombinants showed a significant reduction in vaccine virus shedding but secreted more challenge virus than the other vaccinees. These findings indicate that expression of these cytokines mediates a better control of the vaccine virus replication which, however, interferes with the immunogenicity of the vaccine. In summary, all recombinant viruses were safe and effective, but protection afforded by the recombinants was not improved as compared to vaccination with the parental virus strain GK/D.

Journal of Veterinary Medicine, Series B, 2000

Intestinal lesions were studied in 32 rhesus monkeys experimentally infected with different strai... more Intestinal lesions were studied in 32 rhesus monkeys experimentally infected with different strains of simian immunodeficiency virus SIVmac (251/32H, 251/32H-SPL and 251/MPBL) by light microscopy, transmission and scanning electron microscopy. A specuum of primary and secondary manifestations of SIV-infection were detected. Primary changes included 'SIV-enteropathy' in 12 monkeys and virus-induced syncytial giant cell formation (GCE) of the intestine in two animals. A primary virus-induced enteropathy occurred both as only histologically visible 'SIV-enteropathy' and as 'AIDS-enteropathy' accompanied by clinical signs of enteritis. Secondary opportunistic infections (Balantidzum cob, Cryptospnridium, Trichuris, Trichomonas, Spironucleus, Mycobacteria and Cytomegalovirus) were identified in 27 animals and three monkeys developed malignant lymphomas involving the intestinal tract. Compared to intestinal lesions in HIV-infected patients, differences were found concerning the incidence of GCF and the range of opportunistic infections, with cryptosporidium, cytomegalovirus and mycobacteria occurring in both SIV-infected macaques and AIDS patients. The present observations revealed that SIV-infected rhesus monkeys provide an excellent model both for studies on the pathogenesis of HIV-enteropathy and opportunistic infections and for the development of therapies against cryptosporidial, cytomegalovirus and mycobacteria infection. Comparison of three SIV-strains revealed differences in primary and secondary lesions observed: SlVmac251 /MPBI, was correlated with severe primary SIV-induced pathologic changes and SIVmac251-SPL-infected animals showed a higher incidence of malignant lymphomas.

Virology, 1996

The efficacy of three SIVmac32H gp130 vaccines was compared in rhesus monkeys. Three rhesus monke... more The efficacy of three SIVmac32H gp130 vaccines was compared in rhesus monkeys. Three rhesus monkeys were each immunized over a period of 20 weeks with a total of 600 mg virion-derived gp130 oligomers (O-gp130) mixed with keyhole limpet hemocyanin and emulsified with incomplete Freund's adjuvant. Three other monkeys were infected with 5 1 10 8 PFU of vaccinia virus wild type (VV-wt) while three additional animals received an equivalent dose of VV expressing the gp130 of SIVmac (VV-gp130). At Week 8, the two VV-wt animals received an additional immunization with 100 mg O-gp130 each. All VV-infected animals then received booster immunizations at Weeks 12, 16, and 20 with a total of 300 mg O-gp130 per animal. All animals along with two controls were challenged iv with 50 MID 50 of T-cellgrown SIVmac32H at Week 22. Four weeks after the challenge and thereafter, both controls and one animal from either VV group were infected as demonstrated by polymerase chain reaction (PCR), virus isolation, and antibody response. In contrast, all O-gp130 animals and one animal each from the VV-wt and the VV-gp130 group were completely protected as shown by negative PCR and virus reisolation. One animal of the VV-gp130 group was partially protected, since it remained virus isolation negative but became PCR positive. All protected animals did not develop a secondary antibody response. Six months after the first challenge, the five completely protected animals were reimmunized twice 4 weeks apart with a total of 200 mg O-gp130 per animal. Two weeks later, all animals were challenged with 5 MID 50 of the SIVmac32H/spI prepared from the spleen of an immunized, but unprotected SIV-infected rhesus monkey. After the second challenge, all three control animals and one of the vaccinees became productively infected. In contrast, two animals were completely protected, one from the former O-gp130 and one from the former VV-gp130 group. One animal from the former VV-wt group was only DNA -PCR positive and thus partially protected. Therefore, immunization with virion-derived gp130 oligomers of SIVmac32H can confer protection against the infection with T-cell-grown SIVmac32H as well as the ex vivo isolate SIVmac32H/spI. ᭧

Veterinary Record, 2000

Four groups of calves were vaccinated with a glycoprotein E-negative vaccine for infectious bovin... more Four groups of calves were vaccinated with a glycoprotein E-negative vaccine for infectious bovine rhinotracheitis. Two groups of calves were vaccinated intramuscularly and challenged with a wild-type virus 14 and seven days after being vaccinated. The other two groups were vaccinated intranasally and similarly challenged after four and three days; an unvaccinated control group was also challenged. All four vaccination schedules reduced the incidence of clinical signs and the excretion of wild-type virus, and these reductions occurred as early as three days after the intranasal vaccination even in the absence of neutralising antibodies. Because of its marker characteristics, vaccination with this vaccine would not interfere with the detection of infected cattle during an outbreak, and it should therefore provide a useful tool for emergency vaccination campaigns.

Journal of Medical Primatology, 1994

Following an experimental SIV infection, 11 rhesus monkeys were evaluated to determine the presen... more Following an experimental SIV infection, 11 rhesus monkeys were evaluated to determine the presence of opportunistic infections. Five animals had severe alterations of the hepatobiliary tree, three of which were associated with the presence of numerous Cryptosporidium spp. Subacute to chronic inflammatory changes were observed in the pancreatic ducts of four animals, one without histologic evidence of parasites. In one animal, the inflamed ducts were associated with a chronic interstitial pancreatitis. The rate of Cryptosporidium infection together with hepatic and pancreatic involvement (36%) supports the hypothesis that systemic cryptosporidiosis is the result of a loss of protective mucosal immunity.

Journal of General Virology, 1993

Journal of General Virology, 1996

a complex with another glycoprotein, gL. For a detailed analysis of the function of PrV gH, we is... more a complex with another glycoprotein, gL. For a detailed analysis of the function of PrV gH, we isolated a gH-deficient mutant on transcomplementing gH-expressing cells after insertion of a p-galactosidase expression cassette into a partially deleted gH gene. The absence of gH did not affect primary or secondary attachment of PrV but the mutant was not infectious. The defect in infectivity could partially be overcome by experimentally induced membrane fusion using PEG, which suggests that gH was necessary for fusion between virion and cellular membranes. After intranasal inoculation into mice, the LDso of complemented gH PrV was more than four orders of magnitude higher than that of wild-type PrV. Infection of the respiratory epithelium was much less efficient with complemented gH PrV as compared with rescued PrV, reflecting the lack of direct cell-to-cell spread. Complemented gH PrV was able to penetrate into a few trigeminal and sympathetic first order neurons accessible from the nasal cavity, whereas transneuronal transfer in the second order neurons was not observed. In summary, gH is essential for entry and cell-to-cell spread in cell culture, and for propagation in the nervous system of mice. This substantiates the hypothesis that transneuronal spread in vivo and direct cell-to-cell spread in cell culture are governed by similar mechanisms.

BMC Veterinary Research, 2010

Background: The efficacy of a single dose of an inactivated bovine respiratory syncytial virus (B... more Background: The efficacy of a single dose of an inactivated bovine respiratory syncytial virus (BRSV) -Parainfluenaza type 3 (PI3) -Mannheimia haemolytica (Mh) combination vaccine, in calves positive for maternal antibodies, was established in a BRSV infection study. Results: As expected the single vaccination did not have any effect on the decline of BRSV-specific neutralising or ELISA antibody. The cellular immune system was however primed by the vaccination. In the vaccinated group virus excretion with nasal discharge was reduced, less virus could be re-isolated from lung tissues and the lungs were less affected.

AIDS, 1993

To investigate the role of the anti-cellular immune response in the protection of rhesus macaques... more To investigate the role of the anti-cellular immune response in the protection of rhesus macaques against infection with the simian immunodeficiency virus SIVmac. To determine the biological differences between SIV challenge stocks grown either on human T-cell lines or on monkey peripheral blood mononuclear cells (MPBMC). A protective SIVmac split vaccine was administered to rhesus macaques and their anti-, B- and T-cell response monitored. Vaccinees and controls were challenged with SIVmac grown either on human or on monkey cells. The in vivo replication rate of, and the immune response to, the two viruses was compared. Five rhesus macaques were immunized with a total of 2 mg each of purified SIVmac251/32H grown on the human C8166 T-cell line. The antibody and proliferative T-cell responses were evaluated by enzyme-linked immunosorbent assay and T-cell proliferation assay, respectively. Four protected animals and four controls were reboosted and challenged with MPBMC-grown SIVmac251 (SIVmac251/MPBMC). Cell-free virus load was determined by titration of plasma for SIV infectivity on C8166 cells and antigen with a core antigen capture assay. Protection from virus challenge with C8166-grown SIVmac251/32H or SIVmac251/MPBMC did not correlate with anti-cellular antibodies or proliferative T-cell reactivities. Control animals infected with SIVmac251/MPBMC showed high persistent antigenaemia and high plasma virus titres. Both were absent in controls infected with complement C8166-grown SIVmac251/32H. Whereas the latter always seroconverted against the full panel of viral polypeptides, SIVmac251/MPBMC-infected animals showed a drastically decreased antibody response. Neither the antibody nor the proliferative T-cell response to SIVmac correlates with protection from virus challenge. In contrast to SIVmac251/32H grown on C8166 cells, the MPBMC-grown challenge virus SIVmac251 appears to belong to the 'rapid-high' phenotype, possibly explaining the lack of protection against this SIV.

Acta Veterinaria Hungarica, 2008

The efficacy of an inactivated bovine respiratory syncytial virus (BRSV)--bovine parainfluenza ty... more The efficacy of an inactivated bovine respiratory syncytial virus (BRSV)--bovine parainfluenza type 3 (PI3)--Mannheimia haemolytica (Mh) combination vaccine was examined in two field studies. Calves were vaccinated (i) with the inactivated vaccine, (ii) a modified live/killed viral combination vaccine, or (iii) left unvaccinated. The efficacy of the vaccines was judged by the (i) number of treated animals, (ii) number of individual antibiotic treatments per calf and (iii) mortality rates. After vaccination with the inactivated vaccine, the number of calves requiring antibiotic treatment was significantly lower than in the unvaccinated group (odds ratios: 0.26 first study and 0.53 second study), but differences between vaccination with live/killed combination vaccines and controls were not significant (odds ratios: 0.56 and 0.90, respectively). In both studies, a number of unvaccinated controls died due to respiratory disease (4.6% first and 6.7% second study). By contrast, none of the animals vaccinated with the inactivated vaccine died in the first study and only 3.3% in the second study. The mortality rates for the groups vaccinated with the live vaccine (1.3% and 7.8%) were similar to the unvaccinated controls. In summary, these data demonstrate the efficacy of the inactivated vaccine under field conditions.

Cytotechnology, 2002

The studies described in this report were performed to determine, whether it is possible to produ... more The studies described in this report were performed to determine, whether it is possible to produce live virus vaccines without serum or fractions thereof used during any cell or virus passage, thus completely serum-free. Two viruses were included in the experiments: Bovine Herpesvirus 1 (BHV-1) and Bovine Parainfluenza type 3 virus (PI3). Both viruses were found to grow to satisfactory titers, and to be stable after freeze-drying and subsequent storage at temperatures of +4 degrees C and -20 degrees C for at least one year. Moreover, a vaccine containing serum free produced BHV-1 was tested in a vaccination-challenge experiment. For comparison, a vaccine batch with BHV-1 grown in serum-containing cell culture medium was included in the study. Both vaccine preparations performed equally well and both met the strict requirements as laid down in the European Phamacopeia. Moreover, in two separate experiments the safety of serum-free produced BHV-1 and PI3 after overdose and repeated a...

PLOS Neglected Tropical Diseases, 2016

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that affects domesticated ruminants a... more Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that affects domesticated ruminants and occasionally humans. Classical RVF vaccines are based on formalin-inactivated virus or the live-attenuated Smithburn strain. The inactivated vaccine is highly safe but requires multiple administrations and yearly re-vaccinations. Although the Smithburn vaccine provides solid protection after a single vaccination, this vaccine is not safe for pregnant animals. An alternative live-attenuated vaccine, named Clone 13, carries a large natural deletion in the NSs gene which encodes the major virulence factor of the virus. The Clone 13 vaccine was previously shown to be safe for young lambs and calves. Moreover, a study in pregnant ewes suggested that the vaccine could also be applied safely during gestation. To anticipate on a possible future incursion of RVFV in Europe, we have evaluated the safety of Clone 13 for young lambs and pregnant ewes. In line with the guidelines from the World Organisation for Animal health (Office International des Epizooties, OIE) and regulations of the European Pharmacopeia (EP), these studies were performed with an overdose. Our studies with lambs showed that Clone 13 dissemination within vaccinated animals is very limited. Moreover, the Clone 13 vaccine virus was not shed nor spread to in-contact sentinels and did not revert to virulence upon animal-to-animal passage. Importantly, a large experiment with pregnant ewes demonstrated that the Clone 13 virus is able to spread to the fetus, resulting in malformations and stillbirths. Altogether, our results suggest that Clone 13 can be applied safely in lambs, but that caution should be taken when Clone 13 is used in pregnant animals, particularly during the first trimester of gestation.

Berliner Und Munchener Tierarztliche Wochenschrift, 2010

Control of IBR and BVD should be possible in Europe. Effective vaccines and reliable tools for mo... more Control of IBR and BVD should be possible in Europe. Effective vaccines and reliable tools for monitoring are available. Systematic approach and strict implementation of control measures are essential. Voluntary or mandatory programs are ongoing on regional or national level in a lot of countries. Successful programs put pressure on surrounding regions/countries to initiate control program as well.

Berliner und Münchener tierärztliche Wochenschrift

Berliner und Münchener tierärztliche Wochenschrift

... Makoschey B, Maclachlan J, v Wuijckhuise L, Kirschvink N, dal Pozzo F, Petit H, Kaandorp-Hube... more ... Makoschey B, Maclachlan J, v Wuijckhuise L, Kirschvink N, dal Pozzo F, Petit H, Kaandorp-Huber C, v Rijn P, Sellal E, Oura C, Boinas F, Cavirani S, de Clercq K, Lucientes J, Meijjes CP, Zientara S, Meyer G, Thiry E. Intervet Schering-Plough Animal Health, Boxmeer, The ...

Berliner und Münchener tierärztliche Wochenschrift

Acta Vet Hung, 2008

The efficacy of an inactivated bovine respiratory syncytial virus (BRSV)--bovine parainfluenza ty... more The efficacy of an inactivated bovine respiratory syncytial virus (BRSV)--bovine parainfluenza type 3 (PI3)--Mannheimia haemolytica (Mh) combination vaccine was examined in two field studies. Calves were vaccinated (i) with the inactivated vaccine, (ii) a modified live/killed viral combination vaccine, or (iii) left unvaccinated. The efficacy of the vaccines was judged by the (i) number of treated animals, (ii) number of individual antibiotic treatments per calf and (iii) mortality rates. After vaccination with the inactivated vaccine, the number of calves requiring antibiotic treatment was significantly lower than in the unvaccinated group (odds ratios: 0.26 first study and 0.53 second study), but differences between vaccination with live/killed combination vaccines and controls were not significant (odds ratios: 0.56 and 0.90, respectively). In both studies, a number of unvaccinated controls died due to respiratory disease (4.6% first and 6.7% second study). By contrast, none of the animals vaccinated with the inactivated vaccine died in the first study and only 3.3% in the second study. The mortality rates for the groups vaccinated with the live vaccine (1.3% and 7.8%) were similar to the unvaccinated controls. In summary, these data demonstrate the efficacy of the inactivated vaccine under field conditions.

PLOS Neglected Tropical Diseases, 2016

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that affects domesticated ruminants a... more Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that affects domesticated ruminants and occasionally humans. Classical RVF vaccines are based on formalin-inactivated virus or the live-attenuated Smithburn strain. The inactivated vaccine is highly safe but requires multiple administrations and yearly re-vaccinations. Although the Smithburn vaccine provides solid protection after a single vaccination, this vaccine is not safe for pregnant animals. An alternative live-attenuated vaccine, named Clone 13, carries a large natural deletion in the NSs gene which encodes the major virulence factor of the virus. The Clone 13 vaccine was previously shown to be safe for young lambs and calves. Moreover, a study in pregnant ewes suggested that the vaccine could also be applied safely during gestation. To anticipate on a possible future incursion of RVFV in Europe, we have evaluated the safety of Clone 13 for young lambs and pregnant ewes. In line with the guidelines from the World Organisation for Animal health (Office International des Epizooties, OIE) and regulations of the European Pharmacopeia (EP), these studies were performed with an overdose. Our studies with lambs showed that Clone 13 dissemination within vaccinated animals is very limited. Moreover, the Clone 13 vaccine virus was not shed nor spread to in-contact sentinels and did not revert to virulence upon animal-to-animal passage. Importantly, a large experiment with pregnant ewes demonstrated that the Clone 13 virus is able to spread to the fetus, resulting in malformations and stillbirths. Altogether, our results suggest that Clone 13 can be applied safely in lambs, but that caution should be taken when Clone 13 is used in pregnant animals, particularly during the first trimester of gestation.

Berliner und Münchener tierärztliche Wochenschrift

It should be established, whether animals vaccinated intramuscularly (IM) with a live Bovine herp... more It should be established, whether animals vaccinated intramuscularly (IM) with a live Bovine herpesvirus type 1 (BHV-1) marker vaccine become viremic and/or excrete vaccine virus with nasal discharge. Five cattle, seronegative for BHV-1, were vaccinated with an overdose of the vaccine (Bovilis IBR marker live) via the IM route. Nasal swabs and blood samples were taken at regular intervals and tested for BHV-1 in a virus infectivity assay. In addition, a polymerase chain reaction (PCR) specific for BHV-1 DNA was performed on the blood samples. BHV-1 neutralizing antibody titres were determined in the sera taken prior to the vaccination and four weeks after immunisation. AIl animals were successfully vaccinated as judged by the development of BHV-1 neutralising antibodies. However, all nasal swab samples were tested negative for vaccine virus, and all blood samples were found negative for BHV-1 vaccine virus and BHV-1 specific DNA. From these data it can be concluded that the vaccine ...

Vaccine, 2003

Cytokines play a key role as regulators of the immune response. To elucidate whether the efficacy... more Cytokines play a key role as regulators of the immune response. To elucidate whether the efficacy of a live virus vaccine can be improved by co-expression of cytokines, expression cassettes for bovine interleukins (boIL)-2, -4, -6, and -12 and bovine interferon-gamma (boIFN-␥) were integrated into the glycoprotein E (gE)-locus of the bovine herpesvirus 1 (BHV-1) vaccine virus strain GK/D. Cell culture analyses demonstrated that expression of the cytokines did not impair the replication of the recombinant viruses. To test safety and efficacy, groups of 4-6 months old BHV-1 seronegative calves were vaccinated intranasally with the parental virus strain GK/D or the recombinants, and challenged intranasally 3 weeks later with virulent BHV-1. The animals were monitored for clinical signs, virus excretion and antibody status after vaccination and challenge. All vaccines were well tolerated and protected the immunised calves from clinical disease following challenge, and reduced duration and titres of challenge virus shedding. Calves inoculated with the boIL-6, boIL-12 and boIFN-␥ expressing recombinants showed a significant reduction in vaccine virus shedding but secreted more challenge virus than the other vaccinees. These findings indicate that expression of these cytokines mediates a better control of the vaccine virus replication which, however, interferes with the immunogenicity of the vaccine. In summary, all recombinant viruses were safe and effective, but protection afforded by the recombinants was not improved as compared to vaccination with the parental virus strain GK/D.

Journal of Veterinary Medicine, Series B, 2000

Intestinal lesions were studied in 32 rhesus monkeys experimentally infected with different strai... more Intestinal lesions were studied in 32 rhesus monkeys experimentally infected with different strains of simian immunodeficiency virus SIVmac (251/32H, 251/32H-SPL and 251/MPBL) by light microscopy, transmission and scanning electron microscopy. A specuum of primary and secondary manifestations of SIV-infection were detected. Primary changes included 'SIV-enteropathy' in 12 monkeys and virus-induced syncytial giant cell formation (GCE) of the intestine in two animals. A primary virus-induced enteropathy occurred both as only histologically visible 'SIV-enteropathy' and as 'AIDS-enteropathy' accompanied by clinical signs of enteritis. Secondary opportunistic infections (Balantidzum cob, Cryptospnridium, Trichuris, Trichomonas, Spironucleus, Mycobacteria and Cytomegalovirus) were identified in 27 animals and three monkeys developed malignant lymphomas involving the intestinal tract. Compared to intestinal lesions in HIV-infected patients, differences were found concerning the incidence of GCF and the range of opportunistic infections, with cryptosporidium, cytomegalovirus and mycobacteria occurring in both SIV-infected macaques and AIDS patients. The present observations revealed that SIV-infected rhesus monkeys provide an excellent model both for studies on the pathogenesis of HIV-enteropathy and opportunistic infections and for the development of therapies against cryptosporidial, cytomegalovirus and mycobacteria infection. Comparison of three SIV-strains revealed differences in primary and secondary lesions observed: SlVmac251 /MPBI, was correlated with severe primary SIV-induced pathologic changes and SIVmac251-SPL-infected animals showed a higher incidence of malignant lymphomas.

Virology, 1996

The efficacy of three SIVmac32H gp130 vaccines was compared in rhesus monkeys. Three rhesus monke... more The efficacy of three SIVmac32H gp130 vaccines was compared in rhesus monkeys. Three rhesus monkeys were each immunized over a period of 20 weeks with a total of 600 mg virion-derived gp130 oligomers (O-gp130) mixed with keyhole limpet hemocyanin and emulsified with incomplete Freund's adjuvant. Three other monkeys were infected with 5 1 10 8 PFU of vaccinia virus wild type (VV-wt) while three additional animals received an equivalent dose of VV expressing the gp130 of SIVmac (VV-gp130). At Week 8, the two VV-wt animals received an additional immunization with 100 mg O-gp130 each. All VV-infected animals then received booster immunizations at Weeks 12, 16, and 20 with a total of 300 mg O-gp130 per animal. All animals along with two controls were challenged iv with 50 MID 50 of T-cellgrown SIVmac32H at Week 22. Four weeks after the challenge and thereafter, both controls and one animal from either VV group were infected as demonstrated by polymerase chain reaction (PCR), virus isolation, and antibody response. In contrast, all O-gp130 animals and one animal each from the VV-wt and the VV-gp130 group were completely protected as shown by negative PCR and virus reisolation. One animal of the VV-gp130 group was partially protected, since it remained virus isolation negative but became PCR positive. All protected animals did not develop a secondary antibody response. Six months after the first challenge, the five completely protected animals were reimmunized twice 4 weeks apart with a total of 200 mg O-gp130 per animal. Two weeks later, all animals were challenged with 5 MID 50 of the SIVmac32H/spI prepared from the spleen of an immunized, but unprotected SIV-infected rhesus monkey. After the second challenge, all three control animals and one of the vaccinees became productively infected. In contrast, two animals were completely protected, one from the former O-gp130 and one from the former VV-gp130 group. One animal from the former VV-wt group was only DNA -PCR positive and thus partially protected. Therefore, immunization with virion-derived gp130 oligomers of SIVmac32H can confer protection against the infection with T-cell-grown SIVmac32H as well as the ex vivo isolate SIVmac32H/spI. ᭧

Veterinary Record, 2000

Four groups of calves were vaccinated with a glycoprotein E-negative vaccine for infectious bovin... more Four groups of calves were vaccinated with a glycoprotein E-negative vaccine for infectious bovine rhinotracheitis. Two groups of calves were vaccinated intramuscularly and challenged with a wild-type virus 14 and seven days after being vaccinated. The other two groups were vaccinated intranasally and similarly challenged after four and three days; an unvaccinated control group was also challenged. All four vaccination schedules reduced the incidence of clinical signs and the excretion of wild-type virus, and these reductions occurred as early as three days after the intranasal vaccination even in the absence of neutralising antibodies. Because of its marker characteristics, vaccination with this vaccine would not interfere with the detection of infected cattle during an outbreak, and it should therefore provide a useful tool for emergency vaccination campaigns.

Journal of Medical Primatology, 1994

Following an experimental SIV infection, 11 rhesus monkeys were evaluated to determine the presen... more Following an experimental SIV infection, 11 rhesus monkeys were evaluated to determine the presence of opportunistic infections. Five animals had severe alterations of the hepatobiliary tree, three of which were associated with the presence of numerous Cryptosporidium spp. Subacute to chronic inflammatory changes were observed in the pancreatic ducts of four animals, one without histologic evidence of parasites. In one animal, the inflamed ducts were associated with a chronic interstitial pancreatitis. The rate of Cryptosporidium infection together with hepatic and pancreatic involvement (36%) supports the hypothesis that systemic cryptosporidiosis is the result of a loss of protective mucosal immunity.

Journal of General Virology, 1993

Journal of General Virology, 1996

a complex with another glycoprotein, gL. For a detailed analysis of the function of PrV gH, we is... more a complex with another glycoprotein, gL. For a detailed analysis of the function of PrV gH, we isolated a gH-deficient mutant on transcomplementing gH-expressing cells after insertion of a p-galactosidase expression cassette into a partially deleted gH gene. The absence of gH did not affect primary or secondary attachment of PrV but the mutant was not infectious. The defect in infectivity could partially be overcome by experimentally induced membrane fusion using PEG, which suggests that gH was necessary for fusion between virion and cellular membranes. After intranasal inoculation into mice, the LDso of complemented gH PrV was more than four orders of magnitude higher than that of wild-type PrV. Infection of the respiratory epithelium was much less efficient with complemented gH PrV as compared with rescued PrV, reflecting the lack of direct cell-to-cell spread. Complemented gH PrV was able to penetrate into a few trigeminal and sympathetic first order neurons accessible from the nasal cavity, whereas transneuronal transfer in the second order neurons was not observed. In summary, gH is essential for entry and cell-to-cell spread in cell culture, and for propagation in the nervous system of mice. This substantiates the hypothesis that transneuronal spread in vivo and direct cell-to-cell spread in cell culture are governed by similar mechanisms.

BMC Veterinary Research, 2010

Background: The efficacy of a single dose of an inactivated bovine respiratory syncytial virus (B... more Background: The efficacy of a single dose of an inactivated bovine respiratory syncytial virus (BRSV) -Parainfluenaza type 3 (PI3) -Mannheimia haemolytica (Mh) combination vaccine, in calves positive for maternal antibodies, was established in a BRSV infection study. Results: As expected the single vaccination did not have any effect on the decline of BRSV-specific neutralising or ELISA antibody. The cellular immune system was however primed by the vaccination. In the vaccinated group virus excretion with nasal discharge was reduced, less virus could be re-isolated from lung tissues and the lungs were less affected.

AIDS, 1993

To investigate the role of the anti-cellular immune response in the protection of rhesus macaques... more To investigate the role of the anti-cellular immune response in the protection of rhesus macaques against infection with the simian immunodeficiency virus SIVmac. To determine the biological differences between SIV challenge stocks grown either on human T-cell lines or on monkey peripheral blood mononuclear cells (MPBMC). A protective SIVmac split vaccine was administered to rhesus macaques and their anti-, B- and T-cell response monitored. Vaccinees and controls were challenged with SIVmac grown either on human or on monkey cells. The in vivo replication rate of, and the immune response to, the two viruses was compared. Five rhesus macaques were immunized with a total of 2 mg each of purified SIVmac251/32H grown on the human C8166 T-cell line. The antibody and proliferative T-cell responses were evaluated by enzyme-linked immunosorbent assay and T-cell proliferation assay, respectively. Four protected animals and four controls were reboosted and challenged with MPBMC-grown SIVmac251 (SIVmac251/MPBMC). Cell-free virus load was determined by titration of plasma for SIV infectivity on C8166 cells and antigen with a core antigen capture assay. Protection from virus challenge with C8166-grown SIVmac251/32H or SIVmac251/MPBMC did not correlate with anti-cellular antibodies or proliferative T-cell reactivities. Control animals infected with SIVmac251/MPBMC showed high persistent antigenaemia and high plasma virus titres. Both were absent in controls infected with complement C8166-grown SIVmac251/32H. Whereas the latter always seroconverted against the full panel of viral polypeptides, SIVmac251/MPBMC-infected animals showed a drastically decreased antibody response. Neither the antibody nor the proliferative T-cell response to SIVmac correlates with protection from virus challenge. In contrast to SIVmac251/32H grown on C8166 cells, the MPBMC-grown challenge virus SIVmac251 appears to belong to the 'rapid-high' phenotype, possibly explaining the lack of protection against this SIV.

Acta Veterinaria Hungarica, 2008

The efficacy of an inactivated bovine respiratory syncytial virus (BRSV)--bovine parainfluenza ty... more The efficacy of an inactivated bovine respiratory syncytial virus (BRSV)--bovine parainfluenza type 3 (PI3)--Mannheimia haemolytica (Mh) combination vaccine was examined in two field studies. Calves were vaccinated (i) with the inactivated vaccine, (ii) a modified live/killed viral combination vaccine, or (iii) left unvaccinated. The efficacy of the vaccines was judged by the (i) number of treated animals, (ii) number of individual antibiotic treatments per calf and (iii) mortality rates. After vaccination with the inactivated vaccine, the number of calves requiring antibiotic treatment was significantly lower than in the unvaccinated group (odds ratios: 0.26 first study and 0.53 second study), but differences between vaccination with live/killed combination vaccines and controls were not significant (odds ratios: 0.56 and 0.90, respectively). In both studies, a number of unvaccinated controls died due to respiratory disease (4.6% first and 6.7% second study). By contrast, none of the animals vaccinated with the inactivated vaccine died in the first study and only 3.3% in the second study. The mortality rates for the groups vaccinated with the live vaccine (1.3% and 7.8%) were similar to the unvaccinated controls. In summary, these data demonstrate the efficacy of the inactivated vaccine under field conditions.

Cytotechnology, 2002

The studies described in this report were performed to determine, whether it is possible to produ... more The studies described in this report were performed to determine, whether it is possible to produce live virus vaccines without serum or fractions thereof used during any cell or virus passage, thus completely serum-free. Two viruses were included in the experiments: Bovine Herpesvirus 1 (BHV-1) and Bovine Parainfluenza type 3 virus (PI3). Both viruses were found to grow to satisfactory titers, and to be stable after freeze-drying and subsequent storage at temperatures of +4 degrees C and -20 degrees C for at least one year. Moreover, a vaccine containing serum free produced BHV-1 was tested in a vaccination-challenge experiment. For comparison, a vaccine batch with BHV-1 grown in serum-containing cell culture medium was included in the study. Both vaccine preparations performed equally well and both met the strict requirements as laid down in the European Phamacopeia. Moreover, in two separate experiments the safety of serum-free produced BHV-1 and PI3 after overdose and repeated a...

PLOS Neglected Tropical Diseases, 2016

Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that affects domesticated ruminants a... more Rift Valley fever virus (RVFV) is a mosquito-borne pathogen that affects domesticated ruminants and occasionally humans. Classical RVF vaccines are based on formalin-inactivated virus or the live-attenuated Smithburn strain. The inactivated vaccine is highly safe but requires multiple administrations and yearly re-vaccinations. Although the Smithburn vaccine provides solid protection after a single vaccination, this vaccine is not safe for pregnant animals. An alternative live-attenuated vaccine, named Clone 13, carries a large natural deletion in the NSs gene which encodes the major virulence factor of the virus. The Clone 13 vaccine was previously shown to be safe for young lambs and calves. Moreover, a study in pregnant ewes suggested that the vaccine could also be applied safely during gestation. To anticipate on a possible future incursion of RVFV in Europe, we have evaluated the safety of Clone 13 for young lambs and pregnant ewes. In line with the guidelines from the World Organisation for Animal health (Office International des Epizooties, OIE) and regulations of the European Pharmacopeia (EP), these studies were performed with an overdose. Our studies with lambs showed that Clone 13 dissemination within vaccinated animals is very limited. Moreover, the Clone 13 vaccine virus was not shed nor spread to in-contact sentinels and did not revert to virulence upon animal-to-animal passage. Importantly, a large experiment with pregnant ewes demonstrated that the Clone 13 virus is able to spread to the fetus, resulting in malformations and stillbirths. Altogether, our results suggest that Clone 13 can be applied safely in lambs, but that caution should be taken when Clone 13 is used in pregnant animals, particularly during the first trimester of gestation.

Berliner Und Munchener Tierarztliche Wochenschrift, 2010

Control of IBR and BVD should be possible in Europe. Effective vaccines and reliable tools for mo... more Control of IBR and BVD should be possible in Europe. Effective vaccines and reliable tools for monitoring are available. Systematic approach and strict implementation of control measures are essential. Voluntary or mandatory programs are ongoing on regional or national level in a lot of countries. Successful programs put pressure on surrounding regions/countries to initiate control program as well.

Berliner und Münchener tierärztliche Wochenschrift

Berliner und Münchener tierärztliche Wochenschrift

... Makoschey B, Maclachlan J, v Wuijckhuise L, Kirschvink N, dal Pozzo F, Petit H, Kaandorp-Hube... more ... Makoschey B, Maclachlan J, v Wuijckhuise L, Kirschvink N, dal Pozzo F, Petit H, Kaandorp-Huber C, v Rijn P, Sellal E, Oura C, Boinas F, Cavirani S, de Clercq K, Lucientes J, Meijjes CP, Zientara S, Meyer G, Thiry E. Intervet Schering-Plough Animal Health, Boxmeer, The ...

Berliner und Münchener tierärztliche Wochenschrift