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Biomedical subjects

J Blancou

Publications and source records attributed to J Blancou.

At least 55 records · Page 3Linked to original sources

Effect of strain differences on the potency testing of rabies vaccines in mice.

Antigenic differences between several strains of rabies virus, namely CVS, SAD and Flury (LEP) strains, were studied in cross-challenge experiments or cross-neutralization tests performed on sera of mice immunized with vaccines containing each strain. A typical wild fox virus strain was also included as challenge virus. The strain differences affected the relative potencies of the three vaccines in the European Pharmacopoeia mouse protection test for veterinary rabies vaccines, in that higher antigenic values were obtained when the vaccine strain was homologous to the challenge virus. This observation was confirmed by neutralizing antibody induction in mice.

Animals↗

Interaction between rabies infection and oral administration of vaccinia-rabies recombinant virus to foxes (Vulpes vulpes).

We have investigated the influence of anti-rabies vaccination on the onset of the disease as well as the delay of death in foxes previously infected with rabies virus. A live vaccinia recombinant virus expressing the rabies virus glycoprotein (VVTGgRAB) was used as vaccine. Foxes were divided into six experimental groups of four animals. On day 0, each fox was experimentally infected with a rabies virus suspension. VVTGgRAB was administered by the oral route to each animal of three groups on day 0, 3 or 14. Foxes of other groups were used as unvaccinated controls or received, on day 0, the parental Copenhagen strain of vaccinia virus. The length of post-challenge survival and duration of clinical disease were recorded for each animal tested. All foxes, vaccinated or not, died from rabies as confirmed by fluorescent antibody tests. Animals vaccinated on days 0 and 3 died after a shorter period of incubation than unvaccinated controls. On the other hand, animals vaccinated on day 14 post-challenge died later than control animals. Foxes administered vaccinia virus died at the same time as unvaccinated controls. These results demonstrate that early and late death phenomena, as consequences of interactions between oral vaccination with VVTGgRAB and rabies infection, can occur in foxes.

Administration, Oral↗

Use of recombinant vaccinia-rabies glycoprotein virus for oral vaccination of wildlife against rabies: innocuity to several non-target bait consuming species.

The pathogenicity of a vaccinia recombinant virus expressing the rabies glycoprotein (VVTGgRAB) was tested in several wild animal species which could compete with the natural rabies host, the red fox (Vulpes vulpes) in consuming vaccine baits in Europe. The following species were included in this study: wild boar (Sus scrofa), Eurasian badger (Meles meles), wood mouse (Apodemus sylvaticus), yellow-necked mouse (Apodemus flavicollis), bank vole (Clethrionomys glareolus), common vole (Microtus arvalis), field vole (Microtus agrestis), water vole (Arvicola terrestris), common buzzard (Buteo buteo), kestrel (Falco tinnunculus), carrion crow (Corvus corone), magpie (Pica pica) and jay (Garrulus glandarius). During the observation period, the 107 animals given the VVTGgRAB vaccine orally did not show any clinical signs. Daily monitoring for 28 days and postmortem examination did not result in the detection of pox lesions in the oral mucosa or the skin in mammals or the unfeathered portions of birds. VVTGgRAB seems to multiply in the mammalian species tested, since rabies seroconversion was observed in all of them. Birds failed to develop demonstrable rabies virus-neutralizing antibody. A seroconversion against vaccinia virus was observed in two of four wild boars. Serological results obtained in badgers and wild boars also demonstrates the absence of direct or indirect horizontal transmission of the recombinant virus. The potential of the recombinant virus for the immunization of badgers against rabies also was investigated. Only 50% of the badgers orally administered with 1 x 10(8.3) TCID50 of this vaccine were protected against rabies.

Administration, Oral↗

[Safety and efficacy of an antirabies vaccine consisting of recombinant vaccinia-rabies virus administered orally to the fox, dog and cat].

One of the most promising ways to control rabies in wildlife seems to be the distribution of bait containing an anti-rabies vaccine. So far, the most widely used vaccines were modified live viruses (SAD strain or derivatives). Nevertheless, these strains retain some pathogenicity for non-target species. A novel vaccine was proposed consisting of genetically modified vaccinia virus (strain Copenhagen, thermosensitive ts 26) expressing the foreign glycoprotein G for the rabies virus (strain ERA). Different doses of this recombinant virus were administered orally to 59 foxes (Vulpes vulpes) and their antibodies were titrated before challenge. Foxes (8/8) resisted 1 month after vaccination with 10(7) plaque forming units (PFU), or 4/4 after 18 months. Seroconversion among dogs was 4/4 after vaccination with 10(9,6) PFU and 4/4 among cats after vaccination with 10(8) PFU. These dogs (4/4) and cats (3/4) resisted the challenge 2-3 months after vaccination. This vaccine thus appears to be potent and safe in these species. Its properties are discussed.

Administration, Oral↗

Increased mortality in mice infected with rabies virus and subsequently vaccinated against rabies.

When mice infected 1 or 2 days before by an IM inoculation after high passage of the virus in the species ("challenge virus standard" strain) received an injection of live (Flury) or inactivated virus, their mortality was increased in comparison with unvaccinated controls. In the case of the inactivated virus vaccine, mortality was proportional to the dose of vaccine received. Conversely, when vaccination was carried out in mice recently infected with the same doses of a heterologous strain adapted to foxes, this phenomenon could not be demonstrated. The consequences of these observations on failures of treatment in animals infected with a homologous strain, cases of rabies occurring after vaccination or quality control of vaccines are discussed.

Animals↗

Use of recombinant vaccinia-rabies virus for oral vaccination of fox cubs (Vulpes vulpes, L) against rabies.

Thirteen fox cubs were orally administered 10(7.2) plaque-forming units of live vaccinia-rabies glycoprotein recombinant virus. On Day 28 post-vaccination, all but 1 cub had produced rabies virus antibodies. Twelve animals were intramuscularly inoculated with 10(3.2) mouse intracerebral LD50 of rabies virus suspension on Days 33 (5 foxes), 180 (4 foxes) or 360 (3 foxes) after vaccination. Eleven of them resisted rabies challenge. Unvaccinated foxes, either put in contact with 1 vaccinated animal or used as controls, died after challenge applied on Day 33. The absence of horizontal transmission of this vaccine strain and its innocuity to cubs were also demonstrated.

Administration, Oral↗

Serological survey of herpesvirus infections in wild ruminants of France and Belgium.

The presence of antibodies against bovine herpesvirus 1 (BHV-1), bovid herpesvirus 6 (BHV-6), herpesvirus of Cervidae type 1 (HVC-1), reindeer herpesvirus, bovine herpesvirus 2 (BHV-2) and bovid herpesvirus 4 (BHV-4) was investigated in wild ruminants of France and Belgium between 1981 and 1986. There were no animals serologically positive for BHV-4. Antibodies against BHV-2 were demonstrated in roe deer (Cervus capreolus) (less than 1%) and chamois (Rupicapra rupicapra) (1%) in France. Animals seropositive to the four related viruses (BHV-1, BHV-6, HVC-1, reindeer herpesvirus) were detected in red deer (Cervus elaphus) in France and Belgium (1% and 11%, respectively), in roe deer (less than 1%) from France, in chamois (4%) in France and in ibex (Capra ibex) (4%) from France. The presence of antibodies against HVC-1, especially in red deer from Belgium, may suggest that wild ruminants in continental Europe are now infected with this virus, which previously has been isolated only in Scotland.

Animals↗

Treatment of rabies in mice and foxes with antiviral compounds.

Thirty four chemical compounds were injected into rabies infected mice by intramuscular (i.m.) route. Twenty four compounds such as well known therapeutic agents: amantadine, lipacids, phenol compounds, didemnin-B, procaine, nucleosides analogues (ribavirin, tiazofurin, pyrazofurin) had no effect. Two compounds had a slight effect not justifying to consider them as possible therapeutic agents: selenazofurin and an analogue of ribavirin (RTA). Eight heteropolyanions (HPA), which have a related chemical structure, were efficient providing 100% protection. Nineteen compounds were injected into rabies infected mice by the intracerebral (i.c.) route. Fourteen compounds such as ribavirin, RTA, selenazofurin, tiazofurin and 9 HPA compounds had no effect. Five other HPA compounds (HPA 23-39-46-51-56) were efficient preventing the development of clinical infection in some mice. Whatever was the treatment route, treated surviving mice developed rabies neutralizing antibodies. No proof of viral multiplication was found in their brains. As some HPA compounds did produce a therapeutic effect in mice, two of them HPA 23 and HPA 39 were administered to rabies-infected foxes. In foxes the compounds prolonged the mean survival time and increased the number of survivors. These data suggest that chemotherapy might be worthwhile when vaccination was impossible.

Animals↗

Characterization of a double avirulent mutant of rabies virus and its potency as a vaccine, live or inactivated.

A strain bearing two mutations which abolish the virulence for adult animals after intracerebral or intramuscular inoculation has been constructed from the CVS strain of rabies virus. This apathogenic phenotype is stable after three successive passages of the double mutant in suckling mice brain. Trials of vaccination performed on mice in parallel with the double mutant and CVS both inactivated with beta-propiolactone indicate that the mutant is at least as efficient as CVS. This strain has also been found to be efficient as a live virus vaccine.

Animals↗

[Genetic resistance to rabies infection. Trial of demonstrating the heritability of resistance to the infection (preliminary evaluation on a murine model)].

A model in mice was developed in order to check if a resistance against rabies could be naturally and genetically selected in a line of mammals. A more resistant strain of mice (DBA/2) was identified. However, up to present, all attempts have failed in view to create a resistant strain of swiss mice in breeding individuals surviving to rabies infection.

Animals↗

Beta hemolytic streptococcal infection in red foxes (Vulpes vulpes L.) in France: the natural disease and experimental studies.

Beta hemolytic streptococcal infections, usually of group G and C, were identified in red foxes in France. In a study of 31 animals, septicemia and jaundice were found to be the main signs of the disease. Gross and microscopic lesions consisted of generalized inflammation of viscera and joints, jaundice, cellulitis and abscesses of spleen, liver, lungs and kidneys. The disease was reproduced in foxes by intramuscular inoculation of less than the minimal quantity of bacteria lethal to mice. When challenged, recovered animals were resistant to infection that proved to be lethal to control animals.

Animals↗

Vaccination of young foxes (Vulpes vulpes, L.) against rabies: trials with inactivated vaccine administered by oral and parenteral routes.

Foxes aged between two and three months were vaccinated with an inactivated rabies vaccine. Three immunization procedures were attempted: a first group of animals was parenterally injected while two other groups daily ingested during ten days either an uncoated vaccine (commercially available liquid form: Rabisin) or a coated vaccine (gastro-resistant tablets) associated with a potential enteropathogenic virus (bovine rotavirus). The latter viral association was used in order to see if seroconversion can occur in these conditions. Rabies antibody titres and the length of survival postchallenge were recorded in each treated fox. Seroconversion was observed from approximately day 20 post-vaccination in two groups of cubs: satisfactory antibody titres were found in parenterally vaccinated foxes while lower titres characterized most of the cubs which ingested the uncoated liquid vaccine. Gastro-resistant tablets containing the viral association did not induce seroconversion. It was shown that bovine rotavirus did not multiply in the gut mucosa of young foxes, on the contrary to young dogs. Protection against experimental rabies was partially obtained in parenterally vaccinated foxes.

Animals↗

[Serological response of the dog after primary antirabies vaccination using adjuvant or non-adjuvant vaccines].

The serological responses following a primary vaccination carried out one year before in two groups of dogs which received an inactivated cell culture vaccine containing or not an adjuvant (alumine-hydroxide) are compared. Neutralizing antibody titers assayed in mice, obtained with only one injection of the adjuvanted vaccine are at the same or a greater level than those induced by two injections of the non-adjuvanted vaccine administered two to four weeks apart (statutory schedule of rabies primary vaccination applied in France).

Adjuvants, Immunologic↗

[Experimental bovine rabies: susceptibility, symptoms, humoral immunologic reactions, lesions and virus excretion].

In France, rabies in cattle is transmitted by a bite of a rabid fox. This disease represents a threat for public health. Few written observations concerning bovine rabies have been made. This report describes a model of experimental bovine rabies, necessary for further studies. Consequently, sixteen cattle were inoculated with a street rabies virus suspension into each masseter muscle: ten were challenged with 5 X 10(5) MICLD50, three with 5 X 10(4) MICLD50 and three with 5 X 10(3) MICLD50. The incubation periods, symptomatology, temperature changes, serum neutralizing antibody titers, lesions, excretion and strengths of virus in various tissues were described. Anorexia and adipsia, excessive salivation and characteristic lowings were recognized in more than half of the fifteen rabid cattle. None or few serum neutralizing antibody titers were found. The lesions were not typical. The laboratory diagnosis was difficult when the morbidity period was short. The virus was isolated from salivary mandibular glands of twelve animals and from the saliva of six animals. The animals which had the longest morbidity period were those which had the highest strength of virus in their salivary mandibular glands and in their Ammon's horn.

Animals↗

[The vaccination of cattle against rabies. Antibody kinetics, resistance to challenge three years after vaccination].

The kinetics and the titre of the serum neutralising antibodies have been studied for 55 months, in eight cows already vaccinated against rabies with a commercial vaccine. The titres remained stable during this period and increased after the booster injection 16 months after the primary immunization. The protection obtained with this vaccine was tested. These cattle and five controls were inoculated in each masseter muscle in the 55th month with a street rabies virus suspension (5 x 10(5) MICLD50). None or very low serum neutralising antibody titres were found among the controls. However, the inoculation of street rabies virus elicited an irregular immune response among the vaccinated cows. All the controls died whereas all the cows which had received one booster injection survived.

Animals↗

[Comparison of 4 technics for serologic titration of antibodies against rabies virus in dogs].

Four different serological techniques were used for the determination of antibody levels against rabies virus in 55 vaccinated street dogs: mouse neutralization test (reference), rapid fluorescent focus inhibition test, plaque reduction test and immunoenzymatic test (protein A). The results obtained with each of the last three methods were compared with those obtained with the reference test: correlation coefficients were, respectively, 0.810, 0.812 and 0.682, each being significantly correlated with the others. Therefore the three techniques may each be recommended as an alternative to the mouse neutralization test for routine titrations; the immunoenzymatic method, which titrates not only neutralizing antibodies being, nevertheless, better used as a screening test.

Animals↗