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Recombinant capripoxvirus expressing the hemagglutinin protein gene of rinderpest virus: protection of cattle against rinderpest and lumpy skin disease viruses.

A cDNA clone containing the complete coding sequence of the hemagglutinin (H) protein gene of the RBOK vaccine strain of rinderpest virus, under the control of the vaccinia late promoter p11, was inserted by homologous recombination into the thymidine kinase gene of the KS-1 strain of capripoxvirus. The recombinant virus produced authentic H protein as judged by its electrophoretic mobility, transport to the cell surface of infected lamb testis cells, and reactivity with monoclonal antibodies specific for the H protein of rinderpest virus. The recombinant virus induced significant levels of rinderpest virus neutralizing antibodies in vaccinated cattle and protected them from clinical rinderpest after challenge with a lethal dose of a highly virulent heterologous strain of the virus. Protection was achieved using vaccine doses lower than those used with a similar recombinant expressing the fusion protein gene of rinderpest. The parental KS-1 virus is widely used as a vaccine against capripox viruses and so the rinderpest recombinant acts as a dual vaccine to protect cattle against both rinderpest and lumpy skin disease.

Animals↗

Analyses of baseline survey data on rinderpest in Bahr el Ghazal Province, with proposal of an improved vaccination strategy against rinderpest for southern Sudan.

Results from analyses of baseline surveillance data on rinderpest are used for proposing an improved vaccination strategy against rinderpest in southern Sudan. Sera from 4,074 (47%) of the total sample of 8,565 cattle collected in a series of cross-sectional surveys in 400 cattle camps in the Bahr el Ghazal Province of southern Sudan were tested for rinderpest antibodies using the standard virus neutralisation test (VNT) technique: 77.4% were positive while 22.6% gave negative results. The data were cross-classified according to five variables: herd management, breed, age, sex and geographic region (grazing location). The percentage antibody-positivity level (taken as an approximation of past experience with rinderpest antigen and the corresponding prevalence ratio estimates of relative risk) for each variable are discussed within the context of the known characteristics of immunity to rinderpest in endemic areas and the husbandry practices of the cattle owners in the study area. Results suggest that rinderpest "hot-spots" of transmission and/or low level of herd immunity should be mapped out for concentrated efforts to vaccinate calves and young adults so that the high level of antibody-positivity observed in this study can be maintained and transmission permanently interrupted.

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Rinderpest antibody detected in sheep and goats before an outbreak of rinderpest reported in cattle in northern Tanzania.

In January 1997, serum samples from 1346 adult sheep and goats were tested by a competitive ELISA to determine the prevalence of rinderpest in the northern zone of Tanzania. Seroconversion rates of 20%, 13%, 9%, 7% and 3% in sheep and goats were recorded in Ngorongoro, Monduli, Hai, Arumeru and Simanjiro districts, respectively. The low profile and insidious nature of the rinderpest virus involved caused very mild disease in cattle in some of these area. The mild signs associated with this outbreak of rinderpest resulted in difficulty in its diagnosis. In these circumstances, the presence of rinderpest antibody in sheep and goats served as a valuable and effective indicator of the rinderpest outbreak in cattle.

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A vaccinia virus double recombinant expressing the F and H genes of rinderpest virus protects cattle against rinderpest and causes no pock lesions.

Rinderpest is a highly contagious viral disease of ruminants with greater than 95% morbidity and mortality. We have constructed an infectious vaccinia virus recombinant that expresses both the fusion (F) gene and the hemagglutinin (H) gene of rinderpest virus. The Wyeth strain of vaccinia virus was used for the construction of the recombinant. Cattle vaccinated with the recombinant virus were 100% protected from challenge inoculation with greater than 1000 times the lethal dose of rinderpest virus. No transmission of recombinant vaccinia virus from vaccinated animals to contact animals was observed. The lyophilized form of vaccinia virus is thermostable and allows circumvention of the logistical problems associated with the distribution and administration of vaccines in the arid and hot regions of Asia and Africa. The insertional inactivation of both the thymidine kinase and the hemagglutinin genes of vaccinia virus led to increased attenuation of the virus; this was manifested by the lack of detectable pock lesions in vaccinated animals. This approach may have wide application in the development of safe and efficacious recombinant vaccines for humans and animals. This becomes quite relevant with the concern of the use of vaccinia virus in a population with high incidence of the human immunodeficiency virus.

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Protection of cattle against rinderpest and lumpy skin disease with a recombinant capripoxvirus expressing the fusion protein gene of rinderpest virus.

Cattle were protected against challenge with rinderpest and lumpy skin disease viruses by vaccination with a recombinant capripoxvirus containing the fusion protein (F) gene of rinderpest virus. The minimum protective immunising doses for rinderpest and lumpy skin disease were 5.5 x 10(4) plaque forming units (pfu) and 1.5 x 10(3) pfu, respectively.

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Differentiation of peste des petits ruminants and rinderpest viruses by neutralisation indices using hyperimmune rinderpest antiserum.

Six field isolates believed to be rinderpest viruses and 2 known strains of peste des petits ruminants (PPR) viruses were titrated in the presence of normal rabbit serum and with hyperimmune rinderpest antiserum prepared in rabbits. The known PPR viruses had indices less than 10 whereas 4 of the suspect field isolates had indices greater than a hundred. Two suspect field isolates had indices less than 20; both were collected from small ruminant wild life and are probably PPR viruses.

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Use of the caprinised strain of rinderpest virus for potency testing an attenuated cell culture rinderpest vaccine.

The caprinised strain of rinderpest virus was inoculated into goats to produce a challenge stock. These goats were kept with control animals (goats, sheep, calves). In this trial the caprinised strain was shown to have a mild pathogenicity for goats and it spread to one of two contact goats but not from goats to other species. The caprinised strain was then tested on cattle where a febrile reaction was observed. The caprinised strain also did not spread between cattle. The cattle vaccinated with a freeze-dried vaccine produced from the attenuated Kabete RBKO strain on bovine kidney cells were then challenged with the caprinised strain with good results.

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An epidemiological model of rinderpest. II. Simulations of the behaviour of rinderpest virus in populations.

Fixed parameters for different hypothetical strains of rinderpest virus (RV) and different susceptible populations are described together with details of their derivation. Simulations were then carried out in a computer model to determine the effects that varying these parameters would have on the behaviour of RV in the different populations. The results indicated that virulent strains of RV are more likely to behave in epidemic fashion whereas milder strains tend towards persistence and the establishment of endemicity. High herd immunity levels prevent virus transmission and low herd immunity levels encourage epidemic transmission. Intermediate levels of immunity assist the establishment of endemicity. The virus is able to persist in large populations for longer than in small populations. Different vaccination strategies were also investigated. In areas where vaccination is inefficient annual vaccination of all stock may be the best policy for inducing high levels of herd immunity. In endemic areas and in herds recovering from epidemics the prevalence of clinically affected animals may be very low. In these situations veterinary officers are more likely to find clinical cases by examining cattle for mouth lesions rather than by checking for diarrhoea or high mortalities.

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Immunizing effect of vaccinia virus expressing the nucleoprotein of rinderpest virus on systemic rinderpest virus infection in rabbits.

A recombinant vaccinia virus (RVV) expressing the nucleoprotein (NP) of rinderpest virus (RPV) was examined in rabbits for the involvement of the NP protein in protection from the RPV infection. Despite their production of anti-NP antibody, the RVV-immunized rabbits succumbed to the RPV challenge, although there was a slight delay in the onset of disease after the low-dose challenge. On the other hand, the animals immunized with RVV expressing the hemagglutinin (H) protein of the RPV were completely protected. These results indicate that the NP protein might be not so effective as the H protein for the protection against viremic and systemic infection with RPV.

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Protection of rabbits against lapinized rinderpest virus with purified envelope glycoproteins of peste-des-petits-ruminants and rinderpest viruses.

Haemagglutinin (HA) and fusion (F) proteins of peste-des-petits-ruminants virus (PPRV) and rinderpest virus (RPV) were purified by immunoaffinity chromatography. The purified proteins were characterized by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE). Rabbit hyperimmune sera were raised against the purified HA and F proteins and assayed by enzyme-linked immunosorbent assay (ELISA), haemagglutination-inhibition (HAI) and virus neutralization (VN) tests. The immunized animals were challenged with a virulent lapinized (rabbit-adapted) strain of RPV. Both HA and F proteins of PPRV protected rabbits against a lethal challenge with lapinized RPV. As expected, RPV HA and F proteins also conferred a similar protection against the homologous challenge. The postchallenge antibody responses were of a true anamnestic type.

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Pathogenesis of rinderpest virus infection in rabbits. II. Effect of rinderpest virus on the immune functions of rabbits.

Rinderpest virus infection was shown to induce marked suppression of both humoral antibody response and cell-mediated immunity in rabbits. The virus exhibited a suppressive effect on primary antibody response as indicated by a decrease in numbers of plaque-forming cells (immunoglobulin [Ig]M) and hemagglutinating antibody titers of both IgM and IgG types to sheep red blood cells, whereas there was no detectable effect of the virus on the production of memory cells. Virus-induced suppression of cell-mediated immunity was demonstrated by a decreased rate of proliferative response of peripheral lymphocytes to phytohemagglutinin stimulus and by a depression of delayed-type skin reactions to purified protein derivative. Such suppressive effects were indicated to persist for 14 days or longer. Alteration in phagocytic activity of the reticuloendothelial system was not observed. The relevance of the virus-induced histological lesions in the lymphoid tissues to the virus-induced immunosuppression was discussed.

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