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Long-term sterilizing immunity to rinderpest in cattle vaccinated with a recombinant vaccinia virus expressing high levels of the fusion and hemagglutinin glycoproteins.

Rinderpest is an acute and highly contagious viral disease of ruminants, often resulting in greater than 90% mortality. We have constructed a recombinant vaccinia virus vaccine (v2RVFH) that expresses both the fusion (F) and hemagglutinin (H) genes of rinderpest virus (RPV) under strong synthetic vaccinia virus promoters. v2RVFH-infected cells express high levels of the F and H glycoproteins and show extensive syncytium formation. Cattle vaccinated intramuscularly with as little as 10(3) PFU of v2RVFH and challenged 1 month later with a lethal dose of RPV were completely protected from clinical disease; the 50% protective dose was determined to be 10(2) PFU. Animals vaccinated with v2RVFH did not develop pock lesions and did not transmit the recombinant vaccinia virus to contact animals. Intramuscular vaccination of cattle with 10(8) PFU of v2RVFH provided long-term sterilizing immunity against rinderpest. In addition to being highly safe and efficacious, v2RVFH is a heat-stable, inexpensive, and easily administered vaccine that allows the serological differentiation between vaccinated and naturally infected animals. Consequently, mass vaccination of cattle with v2RVFH could eradicate rinderpest.

Animals↗

Re-emergence of rinderpest as a threat in East Africa since 1979.

Following the success of the JP15 scheme and subsequent annual vaccination campaigns, East Africa was virtually free of rinderpest after the mid 1960s and the disease was considered beaten. However, economic difficulties have recently reduced the expensively maintained vaccine cover and the disease has reappeared throughout much of the region. In 1979 rinderpest was diagnosed in cattle in north eastern Uganda and caused considerable losses until finally brought under control in 1981. No field outbreaks of the disease in cattle have been seen in Kenya but there is serological evidence that the virus has recently infected unvaccinated sheep and goats and wild ungulates in that country. In 1982 rinderpest was confirmed in the laboratory as the cause of death of large numbers of buffaloes in northern Tanzania and implicated as the cause of a rinderpest-like disease of cattle which is reported to be still active in that area. Substantial aid is essential for further control and research if the virus is not again to become endemic in the region.

Africa, Eastern↗

[Primary structure of the F-gene from Rinderpest virus strain K].

Synthesis, cDNA cloning, and nucleotide sequencing of F gene of rinderpest virus strain K was carried out. Analysis of nucleotide sequence showed the only open reading frame coding for protein from 546 a.o. with mol. weight 58.6 kDa. The mean percentage of identical nucleotide residues between F genes of strains K, Kabete O, and L is 76.4% for 5'-untranslated region and 90.5% for translated region, the share of similar amino acid residues in the respective proteins is 92.9%. The structure of restriction site of F0 precursor protein in rinderpest strains with different virulence is similar. Protein F of rinderpest virus strain K has 3 potential glycosylation sites and 13 cystein residues in positions identical to those of F protein of rinderpest strains Kabete O and L.

5' Untranslated Regions↗

Experience with eradicating rinderpest by vaccination.

Rinderpest was such a devastating disease throughout Africa, Asia and Europe, capable of shaping the destinies of governments as well as the livelihoods of producers and consumers alike, that all sectors of society demanded that scientists should strive to develop a means of protecting cattle against the constant risk. The history of vaccination as a tool for the control of rinderpest is a long one but finally spawned a vaccine which certainly ranks highly among the safest and most efficacious of vaccines. Having this Tissue Culture Rinderpest Vaccine (TCRV) available generated aspirations of global rinderpest control and even eradication, which could now be considered feasible.

Animals↗

Cloning and expression of the nucleocapsid gene of virulent Kabete O strain of rinderpest virus in baculovirus: use in differential diagnosis between vaccinated and infected animals.

Rinderpest (RP) is a viral disease of ruminants with > 95% morbidity and mortality. We have cloned the cDNA of the nucleocapsid (N) gene of the virulent Kabete O strain of rinderpest virus (RPVK) and compared its nucleotide and deduced amino acid sequences with those of the N genes of the lapinized strain of rinderpest virus (RPVL), measles virus (MV), and canine distemper virus (CDV). The gene has an open reading frame of 1575 nucleotides and encodes a protein of 525 amino acids with a molecular weight of 59 kDa. The nucleotide sequence of the coding region of the N gene of RPVK is 88.6, 68.9, and 63.2% homologous with N genes of RPVL, MV, and CDV, respectively. We have developed a recombinant baculovirus that expresses the N protein (rRVN) of RPVK in insect cells (Sf9) and larvae (Spodoptera frugiperda). rRVN was used as a coating antigen in an ELISA to distinguish vaccinated animals from those infected with RPV and was also used successfully in the diagnosis of two other morbilliviruses, MV and peste des petits ruminants (PPRV). Crude lysate of a single infected larva (0.2-0.3 g) was sufficient to coat 150 ELISA plates for serological diagnosis of 7200 serum samples in duplicate.

Amino Acid Sequence↗

Humoral antibody response in animals infected with virulent rinderpest virus.

Humoral antibody responses in cattle or rabbits infected with virulent rinderpest virus or lapinised rinderpest virus respectively were assessed. Rinderpest specific antibodies could be first detected 6 days post-infection. No correlation could be established between antibody response and the course of the disease in infected animals during the early stages of infection. The animals with fatal infection either did not respond or had a transient antibody response. A gradual increase in antibody titre from 7 days post-infection was observed in animals which ultimately recovered.

Animals↗

Rapid detection of rinderpest virus antigens by counter-immunoelectrophoresis.

Counter-immunoelectrophoresis was compared with immunodiffusion for its ability to detect rinderpest virus antigens. Counter-immunoelectrophoresis detected antigens in lymph node biopsies from all of 9 infected cattle whereas immunodiffusion detected them in 8 only. Counter-immunoelectrophoresis was between 4 and 16 times more sensitive than immunodiffusion for detecting rinderpest virus antigens in the tissues of diseased animals and could detect positive reactions within 40 min. Counter-immunoelectrophoresis could offer an opportunity for rapid laboratory confirmation of rinderpest.

Animals↗

Microelisa test for detecting antibodies to rinderpest virus antigens.

A microplate enzyme-linked immunosorbent assay (ELISA) was developed which detected antibodies to a soluble antigen prepared from sonicated rinderpest virus-infected cells. The ELISA detected titres of antibody to the virus in the sera of cattle 3 weeks after immunisation with tissue culture rinderpest virus vaccine which were similar to those detected by the virus neutralisation test. The ELISA test shows potential as a rapid and economic technique for screening large numbers of sera for antibody to rinderpest virus.

Animals↗

Reverse phase passive haemagglutination test for the detection of rinderpest antigen.

Reverse phase passive haemagglutination [RPHA] test was applied for the detection of rinderpest antigen in various organs of rinderpest infected cattle. The results of RPHA were compared with counter immunoelectrophoresis [CIE] and single radial haemolysis [SRH] test. RPHA was as sensitive as CIE and SRH in detecting rinderpest antigen.

Animals↗

Confirmation of rinderpest in experimentally and naturally infected cattle using microtitre techniques.

Virulent rinderpest virus was detected by immunoperoxidase staining of microtitre bovine kidney cell cultures within 24 to 48 hours of inoculation with prescapular lymph node and spleen homogenates from experimentally infected steers. Rinderpest virus specific cytopathic effects were evident from 48 hours in microtitre plates and from 72 hours in rolled tube cultures. Nasal and ocular secretions collected from cattle naturally infected with rinderpest and inoculated into bovine kidney cell cultures did not readily yield cytopathic virus in both tubes and microtitre plates, but immunoperoxidase staining of microtitre cultures on the fourth day of inoculation detected replication of virus in cultures inoculated with ocular and nasal secretions from seven of 17 cattle tested.

Animals↗

Immunization with a plasmid DNA expressing rinderpest virus hemagglutinin protein protects rabbits from lethal challenge.

Rinderpest virus haemagglutinin (H) protein was expressed in eukaryotic cells and the plasmid encoding H gene was used for immunization of rabbits. The immunized rabbits were completely protected from lethal challenge with virulent lapinized rinderpest virus. Similar results were also observed in rabbits vaccinated with tissue culture rinderpest (TCRP) vaccine. About 80% of control rabbits vaccinated with empty vector (mock-vaccinated) died after challenge. The thermal reactions and clinical symptoms were less intense in H-DNA vaccinated rabbits as compared to the other two groups. Marked lymphopenia was observed in TCRP and mock-vaccinated rabbits after challenge, however, the H-DNA vaccinated rabbits showed lymphocytosis following challenge. The appearance of lymphocytosis in H-DNA vaccinated rabbits is an interesting finding which needs further investigation.

Animals↗

Identification of epitope expression on the internal proteins of rinderpest virus which is dependent upon virion maturation events.

Monoclonal antibodies (MAb) identified the existence of both maturation-dependent and maturation-independent epitopes on rinderpest virus antigens. The former were divided into (i) post-maturation antigenic determinants, which were dependent upon the maturation of viral antigen into complete virions; and (ii) pre-maturation antigenic determinants, which were only expressed on what appeared to be immature particles before 'budding' into the extracellular environment. Epitope expression could be related to the kinetics of virus production, with the 'post-maturation' sites requiring the production of mature/infectious virions, but the 'pre-maturation' sites being lost when mature virus was formed (these 'pre-maturation' determinants were strongly cell-associated). MAb against the different virion proteins of measles virus, when reacting with rinderpest virus did not demonstrate the same relationship to virion maturation as did the anti-rinderpest virus MAb: the anti-measles virus MAb detected maturation-independent epitopes. This work demonstrates the caution which should be taken when preparing antigens for diagnostic and epidemiological purposes, especially when MAb are being used to identify antigenic differences between isolates, and/or to compare antigenically isolates with vaccine viruses.

Animals↗

Pathomorphological and immunohistological findings in cattle experimentally infected with rinderpest virus isolates of different pathogenicity.

Experimental infection of nine cattle with seven rinderpest virus strains of different pathogenicity resulted in significant variations of clinical signs, morphological lesions and distribution of viral antigen in tissues. The severity of clinical disease was correlated with the extent of tissue alterations and the amount of immunohistologically detectable viral antigen. Both mild and virulent strains of rinderpest share essentially the same tissue tropisms in vivo, i.e. epithelio- and lympho-tropism. However, rinderpest virus isolates of higher pathogenicity showed a more rapid and wider distribution with more extensive lesions than milder strains, which probably accounts for the higher mortality.

Animals↗

A model of lineage-1 and lineage-2 rinderpest virus transmission in pastoral areas of East Africa.

The development of a stochastic, state-transition model of rinderpest transmission dynamics is described using parameter estimates obtained from both laboratory and participatory research. Using serological data, the basic reproduction numbers for lineage-1 rinderpest virus in southern Sudan and for lineage-2 rinderpest virus in Somali livestock were estimated as 4.4 and between 1.2 and 1.9, respectively. The model predictions for the inter-epidemic period in Sudan and Somalia (1.2 and 4.2 years, respectively) were in agreement with analysis of livestock-owner reports (1-2 years and 5 years, respectively).

Animals↗

Systemic and oral immunogenicity of hemagglutinin protein of rinderpest virus expressed by transgenic peanut plants in a mouse model.

Rinderpest causes a devastating disease, often fatal, in wild and domestic ruminants. It has been eradicated successfully using a live, attenuated vaccine from most part of the world leaving a few foci of disease in parts of Africa, the Middle East, and South Asia. We have developed transgenic peanut (Arachis hypogaea L.) plants expressing hemagglutinin (H) protein of rinderpest virus (RPV), which is antigenically authentic. In this work, we have evaluated the immunogenicity of peanut-expressed H protein using mouse model, administered parenterally as well as orally. Intraperitoneal immunization of mice with the transgenic peanut extract elicited antibody response specific to H. These antibodies neutralized virus infectivity in vitro. Oral immunization of mice with transgenic peanut induced H-specific serum IgG and IgA antibodies. The systemic and oral immunogenicity of plant-derived H in absence of any adjuvant indicates the potential of edible vaccine for rinderpest.

Administration, Oral↗

A review of three pathology-based techniques for retrospective diagnosis of rinderpest, with comparison to virus isolation.

Base of tongue, eyelid, and retropharyngeal lymph node were collected from three animals experimentally infected with rinderpest and utilised in a study comparing virus isolation with histopathology, immunohistochemistry, and in situ hybridisation to determine the usefulness of the latter three techniques as retrospective diagnostic aids for this disease. Virus isolation was positive for all nine samples. Histopathology was suggestive in all the tissues and definitive in some. Immunohistochemistry and in situ hybridisation highlighted the presence of rinderpest antigen of rinderpest nucleic acid in all of the sections. However, in situ hybridisation was more specific than immunohistochemistry.

Animals↗

Protection of cattle against rinderpest by intranasal immunisation with a dry powder tissue culture vaccine.

Dry powder tissue culture rinderpest vaccine containing 10(2.5) TCID(50) of virus per dose administered intranasally to cattle induced high titre circulating antibody responses and protection against challenge with a virulent strain of rinderpest virus. A reduction in the dose of virus to 10(1.1) TCID(50) resulted in a failure to elicit detectable antibody responses and a lack of protection. Intranasal powder vaccine offers several advantages over conventional needle-administered aqueous rinderpest vaccine, including greater stability in the absence of a cold chain, reduced risk of 'needle transfer' of other microbial agents present in the vaccinated herd and lower cost.

Administration, Intranasal↗

Rinderpest.

Rinderpest, also known as cattle plague, was for centuries the most dreaded bovine plague known and one that changed the course of history and still seriously compromises trade. It can lay waste not only to farming communities but the wildlife heritage of countries also is threatened because its broad host spectrum extends across cattle, Asian buffaloes, yaks, and many other artiodactyls, both domesticated and wild, including swine. This article provides a brief history of rinderpest before describing its clinical, pathologic, epidemiologic, and diagnostic features. In dealing with control, the prospects for total eradication are described in the context of the Global Rinderpest Eradication Programme, which is on target to achieve that goal by 2010--the first time that an animal disease will have been eradicated.

Animals↗