Long term immunity in African cattle vaccinated with a recombinant capripox-rinderpest virus vaccine

Ngichabe, Christopher; Wamwayi, H.; Ndungu, E. K.; Mirangi, P. K.; Bostock, Christopher J.; Black, D. N.; Barrett, Thomas

doi:10.1017/s0950268801006513

Cited by 43 publications

(27 citation statements)

References 19 publications

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“…Conversely, when higher amounts of unmodified polymerases were expressed, CAT activity was decreased or virtually abolished in the case of the EGFP-tagged RdRp. Quantitative PCR has been used to propose a model of kinetics of RNA synthesis and to determine the processivity of both the Progression of rinderpest disease has been well described in both naturally and experimentally infected animals (32,52). As rRPV KO L-RREGFPR showed no growth impairment in vitro, we were interested to see if this was paralleled in animals and if virulence was retained.…”

Section: Discussionmentioning

confidence: 99%

Rational Attenuation of a Morbillivirus by Modulating the Activity of the RNA-Dependent RNA Polymerase

Brown

Rima

Allen

et al. 2005

J Virol

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Negative-strand RNA viruses encode a single RNA-dependent RNA polymerase (RdRp) which transcribes and replicates the genome. The open reading frame encoding the RdRp from a virulent wild-type strain of rinderpest virus (RPV) was inserted into an expression plasmid. Sequences encoding enhanced green fluorescent protein (EGFP) were inserted into a variable hinge of the RdRp. The resulting polymerase was autofluorescent, and its activity in the replication/transcription of a synthetic minigenome was reduced. We investigated the potential of using this approach to rationally attenuate a virus by inserting the DNA sequences encoding the modified RdRp into a full-length anti-genome plasmid from which a virulent virus (rRPV KO ) can be rescued. A recombinant virus, rRPV KO L-RREGFPR, which grew at an indistinguishable rate and to an identical titer as rRPV KO in vitro, was rescued. Fluorescently tagged polymerase was visible in large cytoplasmic inclusions and beneath the cell membrane. Subcutaneous injection of 10 4 TCID 50 of the rRPV KO parental recombinant virus into cattle leads to severe disease symptoms (leukopenia/diarrhea and pyrexia) and death by 9 days postinfection. Animals infected with rRPV KO L-RREGFPR exhibited transient leukopenia and mild pyrexia, and the only noticeable clinical signs were moderate reddening of one eye and a slight ocular-nasal discharge. Viruses that expressed the modified polymerase were isolated from peripheral blood lymphocytes and eye swabs. This demonstrates that a virulent morbillivirus can be attenuated in a single step solely by modulating RdRp activity and that there is not necessarily a correlation between virus growth in vitro and in vivo.Morbilliviruses cause significant levels of disease in humans and animals throughout the world. For example, the human pathogen measles virus (MV) infects over 40 million individuals per annum and leads to the death of around 800,000 children. The classical course of disease progression is difficult to mimic comprehensively in tractable animal models as the virus has a highly restricted host range. A number of nonhuman primate models have been developed which reproduce many, but not all, aspects of the human disease. However, each has some limitations and they are all dead-end hosts (2,45,47). This limitation has led to the development of a range of smallanimal models, which are useful but tend to reflect only limited aspects of the human disease (29,30,33,37,40). These models are augmented by others which use closely related morbilliviruses, such as rinderpest virus (RPV) or canine distemper virus (CDV), to infect natural hosts such as cattle and ferrets (18, 49, 52). Although many aspects of MV infection of humans are mirrored in the pathogenesis of CDV and RPV, each has its characteristic pattern of disease progression. Thus, wild-type CDV is much more likely to infect the central nervous system than MV, whereas RPV has not been found to infect the central nervous system. In contrast, wild-type RPV has a particular propensity to infec...

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Section: Discussionmentioning

confidence: 99%

Rational Attenuation of a Morbillivirus by Modulating the Activity of the RNA-Dependent RNA Polymerase

Brown

Rima

Allen

et al. 2005

J Virol

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“…Inevitably, there will be regulatory problems with approving these vaccines in capripoxvirus‐free regions, as currently most of these recombinant vaccines do not have the appropriate companion tests available to differentiate infected from vaccinated animals (van Oirschot, 1999). As capripoxviruses are antigenically conserved, a single vaccine can generate long‐lasting immunity (Ngichabe et al., 2002) and offer protection in sheep, goats and cattle for all capripoxvirus isolates (Kitching, 2003). Capripoxviruses have a single serotype, do not cause persistent infection, have a limited host range and vaccines are available that provide life‐long immunity.…”

Section: Vaccinesmentioning

confidence: 99%

Capripoxviruses: An Emerging Worldwide Threat to Sheep, Goats and Cattle

Babiuk

Bowden

Boyle

et al. 2008

Transboundary and Emerging Diseases

340

310

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Capripoxviruses are the cause of sheeppox, goatpox and lumpy skin disease (LSD) of cattle. These diseases are of great economic significance to farmers in regions in which they are endemic and are a major constraint to international trade in livestock and their products. Although the distribution of capripoxviruses is considerably reduced from what it was even 50 years ago, they are now expanding their territory, with recent outbreaks of sheeppox or goatpox in Vietnam, Mongolia and Greece, and outbreaks of LSD in Ethiopia, Egypt and Israel. Increased legal and illegal trade in live animals provides the potential for further spread, with, for instance, the possibility of LSD becoming firmly established in Asia. This review briefly summarizes what is known about capripoxviruses, including their impact on livestock production, their geographic range, host-specificity, clinical disease, transmission and genomics, and considers current developments in diagnostic tests and vaccines. Capripoxviruses have the potential to become emerging disease threats because of global climate change and changes in patterns of trade in animals and animal products. They also could be used as economic bioterrorism agents.

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“…With that in mind, the attenuated capripoxvirus strain KS-1 was used to develop an effective recombinant rinderpest vaccine expressing the fusion (F) and hemagglutinin (H) proteins of the rinderpest virus (22,23). This vaccine has now been tested and shown to be effective in long-term trials (19,20). Capripoxviruses are present in Asia, the Middle East, and Africa.…”

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confidence: 99%

Development of a Dual Recombinant Vaccine To Protect Small Ruminants against Peste-des-Petits-Ruminants Virus and Capripoxvirus Infections

Berhe

Minet

Goff

et al. 2003

J Virol

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110

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Long term immunity in African cattle vaccinated with a recombinant capripox-rinderpest virus vaccine

Cited by 43 publications

References 19 publications

Rational Attenuation of a Morbillivirus by Modulating the Activity of the RNA-Dependent RNA Polymerase

Rational Attenuation of a Morbillivirus by Modulating the Activity of the RNA-Dependent RNA Polymerase

Capripoxviruses: An Emerging Worldwide Threat to Sheep, Goats and Cattle

Development of a Dual Recombinant Vaccine To Protect Small Ruminants against Peste-des-Petits-Ruminants Virus and Capripoxvirus Infections

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