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Biomedical subjects

P P Pastoret

Publications and source records attributed to P P Pastoret.

At least 19 recordsLinked to original sources

Salivary excretion of rabies virus by healthy vampire bats.

Salivary excretion of rabies virus was evaluated in 14 adult vampire bats (Desmodus rotundus) intramuscularly injected with a large dose (10(6) MICLD50) of vampire rabies virus variant CASS88. Saliva samples were obtained from surviving bats every other day for 30 days, then weekly for 2 months, and finally 1 and 2 years later. Rabies virus was isolated in murine neuroblastoma cells and in randomly selected cases by PCR. Rabies virus was not detected in the saliva of any of the 11 animals that succumbed (somewhat early) to rabies challenge, nor in the control bats. In contrast, virus was detected early, and only once (days 6, 6 and 21) in each of the three animals that survived rabies challenge and remained healthy for at least 2 years after challenge. At that time even vigorous dexamethasone and cyclosporine administration failed to provoke further viral excretion.

Animals↗

[Foot-and-mouth disease:: an old disease--new solutions].

The recent outbreak of foot-and-mouth disease in United Kingdom provoked a crisis in the European Union with deleterious consequences not only for livestock industry. Public opinion is more and more concerned about stamping out measures used to control the disease even with previously vaccinated animals. Presently the trend is to "vaccinate for life". This policy change requires to improve vaccines and diagnostic tools. It is not foreseen nevertheless to come back to a generalized vaccination of cattle as it was the case previously in continental Europe, despite its efficacy. According to the new policy, it will only be emergency vaccination to control outbreaks; it will compulsorily use inactivated vaccines. The vaccines will have to confer quickly a strong (sterile) protection against several serotypes during the same outbreak. Several serotypes could be involved in case of agroterrorism. Another feature of foot-and-mouth virus infection is the generation of asymptomatic carriers of wild virus after infection even in previously vaccinated animals. In order to get round this problem, so-called "marker vaccines" associated with a companion diagnostic test are developed: it aims to be able to differentiate simply vaccinated animals from infected ones, whether they were previously vaccinated or not. These vaccines are presently highly purified inactivated vaccines and the companion diagnostic test is based upon the detection of specific antibodies directed against virus-induced non-structural proteins. These antibodies should not be detected in simply vaccinated animals. This technology takes into account the fact that foot-and-mouth disease virus multiplication implies the synthesis of a polyprotein subsequently cleaved. It allows to certify the absence of infection at a herd level not yet at an individual level. Another research trend is to identify virus receptors in animals in order to better understand the pathogenesis of the infection and the reasons why some animals become asymptomatic carriers of wild virus after infection.

Animals↗

Veterinary vaccines for animal and public health.

Vaccination is without doubt the most useful single measure available to prevent animal infectious diseases. The advantages of vaccination are numerous. It is the only available method to prevent, or sometimes cure, viral animal infections in the absence of broad spectrum antivirals and avoids the alternative of mass slaughtering of livestock. Antibiotic or anthelmintic resistance, and the problem of pharmaceutical residues, promote the use of vaccines rather than chemotherapy. Vaccines are environmentally friendly and increase animal welfare by preventing suffering from disease resulting from treatment for a cure which may result in antibiotic resistance and pharmaceutical residues in food. For the management of livestock health vaccines are the best tool to achieve sustainability. Veterinary vaccines cannot only be used to protect animal health but also human health from zoonotic infections through animal vaccination as exemplified by wildlife vaccination against rabies. In animal health the focus is now on animal infections rather than on animal diseases. Vaccines should be designed to prevent infection rather than to prevent clinical signs of disease and should, wherever possible, produce sterile immunity. Available technologies allow us to design "marker" vaccines together with their companion diagnostic tests which permit the distinction between vaccinated and infected animals even if the latter were previously vaccinated. Examples will be given of foot-and-mouth disease, classical swine fever, and herpesvirus infections of livestock such as pseudorabies or infectious bovine rhinotracheitis where carrier state or latency remain an issue after vaccination.

Animal Diseases↗

Assessment of the clinical and virological protection provided by a commercial inactivated bovine viral diarrhoea virus genotype 1 vaccine against a BVDV genotype 2 challenge.

A new genotype of bovine viral diarrhoea virus (BVDV), designated BVDV-2, has emerged in the last decade and in recent years the prevalence of BVDV-2 strains has increased. A vaccination-challenge study was carried out to determine the cross-protective efficacy of a commercial inactivated vaccine containing a BVDV-1 strain. A group of five BVDV-free calves was vaccinated twice and a second group of five calves served as negative controls. Two months after the first vaccination, all the calves were challenged intranasally with BVDV-2 strain BVD890. The clinical signs of disease, the changes in haematological variables and the level of viraemia were significantly less in the vaccinated group.

Animals↗

Regulatory considerations for emergency use of vaccines in the European Union.

From a regulatory perspective foot-and-mouth disease (FMD) vaccines represent a special case due to the number and antigenic diversity of strains that might be used alone or in combination within the context of an authorisation. New guidelines have been developed proposing that an FMD vaccine should be defined as a formulation of ingredients including defined amounts of one or more antigens that vary only in the number and types of antigen present. These new guidelines are in line with those previously proposed for equine influenza vaccines. Slaughter policies being less and less popular in the European Union, there is a tendency to use so-called marker vaccines associated with a companion diagnostic test. Such methodology has already been used for vaccination against pseudo-rabies and infectious bovine rhinotracheitis. Sub-unit marker vaccines against classical swine fever have also been developed; such vaccines are also envisaged against foot-and-mouth disease; it would permit, if satisfying defined criteria, to distinguish vaccinated from infected animals.

Animal Diseases↗

Kinetics of humoral immune response after rabies VR-G oral vaccination of captive fox cubs (Vulpes vulpes) with or without maternally derived antibodies against the vaccine.

In western Europe during the spring, the largest proportion of fox populations are cubs and the key to successful rabies oral vaccination campaigns is cub vaccination. In this paper we report on studies of the serology of 93 fox (Vulpes vulpes) cubs born to unvaccinated and orally vaccinated captive vixens, some of which were orally vaccinated at 30 or at 90 days of age with the vaccinia recombinant vaccine (VR-G) that expresses the rabies virus glycoprotein. The duration of cub passively acquired antibody, the development of immune responses to oral vaccination at either 30 or 90 days of age, possible interference between passive and active immunity to such vaccination and resistance to a potentially lethal rabies challenge dose when five months old were measured. The study showed that rabies neutralising antibody can be passed to their cubs by vixens orally vaccinated with VR-G during pregnancy. Maternally derived antibody titres in cubs declined with time and disappeared by 45-75 days after birth. Thirty days old cubs serologically responded to oral vaccination. No interference between antibody of maternal origin and active immunity conferred by VR-G oral vaccination or between antibody of maternal origin and protection was observed. Thus, very young cub immunisation against rabies with VR-G per os is possible whatever the immune status of their mothers. Provided a vaccine-bait suitable for such young cubs exists, oral vaccination at den entrances with VR-G is a feasibility.

Administration, Oral↗

Humoral and cell-mediated immune responses of foxes (Vulpes vulpes) after experimental primary and secondary oral vaccination using SAG2 and V-RG vaccines.

Humoral and cell-mediated immune responses of 36 captive foxes to two oral vaccines against rabies currently used for foxes in Europe were studied. The Street Alabama Dufferin (SAD) mutant Gif (SAG2) vaccine has been selected by double mutation from the SAD virus. The vaccinia recombinant virus (V-RG) expresses the rabies glycoprotein. Both vaccines induce similar humoral and cell-mediated responses after primary and secondary oral administration. We observed a typical anamnestic response, although of a limited duration, after the booster vaccination. Therefore, our results suggested that two successive oral vaccination campaigns should not significantly improve the immunisation of foxes. Lymphocyte in vitro proliferative response to the SAD antigen highlighted the presence in blood of a T-cell specific memory 6 months after vaccination. The synthesis of several vulpine cytokines was detected in peripheral blood mononuclear cells (PBMC) stimulated by SAD antigen via reverse transcription polymerase chain amplification. The data showed a concomitant expression of interleukin (IL)-4 and interferon-gamma in PBMC of vaccinated foxes. No change was detected in the level of IL-2, IL-10 and IL-12 synthesis, whereas the pro-inflammatory cytokine tumour necrosis factor-alpha seemed involved in the activation of naive T lymphocytes.

Administration, Oral↗

Genetic characterization of Puumala hantavirus strains from Belgium: evidence for a distinct phylogenetic lineage.

Puumala hantavirus (PUUV) sequences were recovered from red bank voles (Clethrionomys glareolus) trapped between 1996 and 1998 in four localities of southern Belgium: Thuin, Montbliart, Momignies and Couvin. In addition, three PUUV isolates originating from bank voles trapped in the 1980s in southern (Montbliart) and northern (Turnhout) Belgium were genetically characterized. Analysis of the complete S and partial M segment sequences showed that the Belgian PUUV strains constitute a genetic lineage, distinct from other known PUUV lineages from Europe and Japan. This lineage also includes a wild strain (Cg-Erft) originating from a neighbouring area of Germany. Within the Belgian lineage, geographical clustering of genetic variants was observed. In the Montbliart site, the range of diversity between the most temporally distant strains (from 1986 and 1996-1998) was higher than between those from 1996 and 1998, suggesting slight genetic drift via accumulation of neutral or quasi-neutral substitutions with time.

Animals↗

Diversity among bovine pestiviruses.

Bovine viral diarrhoea virus (BVDV) isolates are characterized by an important genetic, antigenic and pathogenic diversity. The emergence of new hypervirulent BVDV strains in North America has provided clear evidence of pathogenic differences between BVDV strains. The origin of BVDV diversity is related to high mutation rate occurring in RNA viruses but the consequences of mutations obviously depend on the genes which are involved. Mutations in genes encoding for structural proteins of immunological importance may have practical implications. Knowledge of BVDV diversity is important for understanding the wide variety of pathogenesis of diseases caused by the virus, for monitoring the epidemiology of the different types and for the design of optimum laboratory tests and vaccines. This review focuses on the origin and consequences of BVDV diversity with regard to pathogenesis, biotypes, and antigenic and genetic variations.

Animals↗

[Mad cow disease and the new variant of Creutzfeldt-Jakob disease].

Bovine spongiform encephalopathy and the new variant of Creutzfeldt-Jakob disease (vCJD) belong to a family of similar diseases under the name of transmissible spongiform encephalopathies (TSE). It is demonstrated that the agent responsible for bovine spongiform encephalopathy (BSE) is also responsible for the new variant of Creutzfeldt-Jakob in man. This contribution describes the main characteristics of the two diseases.

Animals↗

[Hantavirus infection epidemiology in Belgium].

In Europe, Puumala (PUU) is a hantavirus responsible for a human disease called nephropathia epidemica and its natural reservoir is the red bank vole, (Clethrionomys glareolus). Although the population densities and the prevalence rates of infection were high in red bank voles in southern Belgium during the 1996 and 1999 epidemic years, the percentages of infected rodents were low in 1997 and 1998, when only a few positive sites were found. Antibodies against PUU virus were mainly detected in the red bank vole but also in the wood mouse (Apodemus sylvaticus) and the red fox (Vulpes vulpes). The analysis of genomic sequences has shown that the Belgian viruses and the German strain Erft constitute a genetic lineage well separated from the other European PUU strains.

Animals↗

A multipotential beta -1,6-N-acetylglucosaminyl-transferase is encoded by bovine herpesvirus type 4.

The beta-1,6-N-acetylglucosaminyltransferase (beta1,6GnT) gene family encodes enzymes playing crucial roles in glycan synthesis. Important changes in beta1,6GnT expression are observed during development, oncogenesis, and immunodeficiency. The most characterized beta1,6GnTs in this gene family are the human (h) C2GnT-L and h-IGnT, which have core 2 [Galbeta1-->3(GlcNAcbeta1-->6)GalNAc] and I branching [GlcNAcbeta1-->3(GlcNAcbeta1-->6)Gal] activities, respectively. Recently, h-C2GnT-M was shown to be unique in forming core 2, core 4 [GlcNAcbeta1-->3(GlcNAcbeta1-->6)GalNAc], and I structures. To date, the beta1,6GnT gene family has been characterized only in mammals. Here, we describe that bovine herpesvirus type 4 (BHV-4) encodes a beta1,6GnT expressed during viral replication and exhibiting all of the core 2, core 4, and I branching activities. Sequencing of the BHV-4 genome revealed an ORF, hereafter called BORFF3-4, encoding a protein (pBORFF3-4) exhibiting 81.1%, 50.7%, and 36.6% amino acid identity with h-C2GnT-M, h-C2GnT-L, and h-IGnT, respectively. Reverse transcriptase-PCR analysis revealed that BORFF3-4 is expressed during BHV-4 replication. Expression of BORFF3-4 in Chinese hamster ovary cells directed the expression of core 2 branched oligosaccharides and I antigenic structures on the cell surface. Moreover, a soluble form of pBORFF3-4 had core 4 branching activity in addition to core 2 and I branching activities. Finally, infection of a C2GnT-negative cell line with BHV-4 induced expression of core 2 branched oligosaccharides. This study extends the beta1,6GnT gene family to a viral gene and provides a model to study the biological functions of a beta1,6GnT in the context of viral infection.

Amino Acid Sequence↗

An approach to the control of disease transmission in pig-to-human xenotransplantation.

Although several major immunologic hurdles need to be overcome, the pig is currently considered the most likely source animal of cells, tissues and organs for transplantation into humans. Concerns have been raised with regard to the potential for the transfer of infectious agents with the transplanted organ to the human recipient. This risk is perceived to be increased as it is likely that the patient will be iatrogenically immunocompromised and the organ-source pig may be genetically engineered in such a way to render its organs particularly susceptible to infection with human viruses. Furthermore, the risk may not be restricted to the recipient, but may have consequences for the health of others in the community. The identification of porcine endogenous retroviruses and of hitherto unknown viruses have given rise to the most concern. We document here the agents we believe should be excluded from the organ-source pigs. We discuss the likelihood of achieving this aim and outline the potential means by which it may best be achieved.

Animals↗

Virus neutralizing antibodies against a panel of 18 BVDV isolates in calves vaccinated with Rispoval RS-BVD.

Seven of nine colostrum-deprived calves, free from infection with bovine virus diarrhoea virus (BVDV), were vaccinated with Rispoval RS-BVD on two occasions, 21 days apart, while the other two were kept as BVDV infection controls. The virus neutralizing (VN) serum antibodies induced by vaccination were tested for their ability to neutralize 18 European BVDV isolates, including laboratory reference strains and recent field isolates, both cytopathic and non-cytopathic biotypes as well as genotypes I and II. The strains were isolated in Belgium, France, Germany and the United Kingdom. While there were large variations in the vaccine-induced VN titres of the individual calves against all the strains, e.g. the titres against Osloss NCP, the European reference strain ranged from 1.7 to 6.7 (1:log2), serum from each animal was capable of neutralizing between nine and all 18 of the strains tested. Nevertheless, from the results of this study, it can be concluded that in colostrum-deprived BVDV seronegative calves, Rispoval RS-BVD can stimulate the production of VN antibodies capable of neutralizing a wide range of antigenically diverse European isolates of BVDV, including genotypes I and II.

Animals↗

Differences in experimental virulence of bovine viral diarrhoea viral strains isolated from haemorrhagic syndromes.

In the late 1980s, a new hypervirulent and epidemic form of bovine viral diarrhoea virus (BVDV) infection appeared in North America. A similar but sporadic syndrome was later reported in Europe. To compare the pathogenic characters of the North American and European hypervirulent strains, we inoculated BVDV naïve calves with BVDV strains isolated from haemorrhagic syndromes originating in Belgium, France and the USA. The experimental procedure comprised daily clinical examination and measurement of blood and virological parameters. The American BVD890/256 strain induced severe thrombocytopaenia, profuse diarrhoea and pneumonia in all calves, indicating that hypervirulent BVDV could be the primary infectious agent of pneumonia. Interestingly, a strong correlation was observed between the intense viraemia and a decreased platelet count. None of the European strains tested induced significant pathological signs, although isolated from cases presenting haemorrhagic syndrome.

Animals↗