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      Comparative Evaluation of Lumpy Skin Disease Virus-Based Live Attenuated Vaccines

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          Abstract

          Vaccines form the cornerstone of any control, eradication and preventative strategy and this is no different for lumpy skin disease. However, the usefulness of a vaccine is determined by a multiplicity of factors which include stability, efficiency, safety and ease of use, to name a few. Although the vaccination campaign in the Balkans against lumpy skin disease virus (LSDV) was successful and has been implemented with success in the past in other countries, data of vaccine failure have also been reported. It was therefore the purpose of this study to compare five homologous live attenuated LSDV vaccines (LSDV LAV) in a standardized setting. All five LSDV LAVs studied were able to protect against a challenge with virulent LSDV. Aside from small differences in serological responses, important differences were seen in side effects such as a local reaction and a Neethling response upon vaccination between the analyzed vaccines. These observations can have important implications in the applicability in the field for some of these LSDV LAVs.

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          Most cited references58

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          Review: Capripoxvirus Diseases: Current Status and Opportunities for Control

          Summary Lumpy skin disease, sheeppox and goatpox are high‐impact diseases of domestic ruminants with a devastating effect on cattle, sheep and goat farming industries in endemic regions. In this article, we review the current geographical distribution, economic impact of an outbreak, epidemiology, transmission and immunity of capripoxvirus. The special focus of the article is to scrutinize the use of currently available vaccines to investigate the resource needs and challenges that will have to be overcome to improve disease control and eradication, and progress on the development of safer and more effective vaccines. In addition, field evaluation of the efficacy of the vaccines and the genomic database available for poxviruses are discussed.
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            The genomes of sheeppox and goatpox viruses.

            Sheeppox virus (SPPV) and goatpox virus (GTPV), members of the Capripoxvirus genus of the Poxviridae, are etiologic agents of important diseases of sheep and goats in northern and central Africa, southwest and central Asia, and the Indian subcontinent. Here we report the genomic sequence and comparative analysis of five SPPV and GTPV isolates, including three pathogenic field isolates and two attenuated vaccine viruses. SPPV and GTPV genomes are approximately 150 kbp and are strikingly similar to each other, exhibiting 96% nucleotide identity over their entire length. Wild-type genomes share at least 147 putative genes, including conserved poxvirus replicative and structural genes and genes likely involved in virulence and host range. SPPV and GTPV genomes are very similar to that of lumpy skin disease virus (LSDV), sharing 97% nucleotide identity. All SPPV and GTPV genes are present in LSDV. Notably in both SPPV and GTPV genomes, nine LSDV genes with likely virulence and host range functions are disrupted, including a gene unique to LSDV (LSDV132) and genes similar to those coding for interleukin-1 receptor, myxoma virus M003.2 and M004.1 genes (two copies each), and vaccinia virus F11L, N2L, and K7L genes. The absence of these genes in SPPV and GTPV suggests a significant role for them in the bovine host range. SPPV and GTPV genomes contain specific nucleotide differences, suggesting they are phylogenetically distinct. Relatively few genomic changes in SPPV and GTPV vaccine viruses account for viral attenuation, because they contain 71 and 7 genomic changes compared to their respective field strains. Notable genetic changes include mutation or disruption of genes with predicted functions involving virulence and host range, including two ankyrin repeat proteins in SPPV and three kelch-like proteins in GTPV. These comparative genomic data indicate the close genetic relationship among capripoxviruses, and they suggest that SPPV and GTPV are distinct and likely derived from an LSDV-like ancestor.
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              Quantification of lumpy skin disease virus following experimental infection in cattle.

              Lumpy skin disease along with sheep pox and goatpox are the most serious poxvirus diseases of livestock, and are caused by viruses that belong to the genus Capripoxvirus within the subfamily Chordopoxvirinae, family Poxviridae. To facilitate the study of lumpy skin disease pathogenesis, we inoculated eight 4- to 6-month-old Holstein calves intravenously with lumpy skin disease virus (LSDV) and collected samples over a period of 42 days for analysis by virus isolation, real-time PCR and light microscopy. Following inoculation, cattle developed fever and skin nodules, with the extent of infection varying between animals. Skin nodules remained visible until the end of the experiment on day post-inoculation (DPI) 42. Viremia measured by real-time PCR and virus isolation was not observed in all animals but was detectable between 6 and 15 DPI. Low levels of viral shedding were observed in oral and nasal secretions between 12 and 18 DPI. Several tissues were assessed for the presence of virus at DPI 3, 6, 9, 12, 15, 18 and 42 by virus isolation and real-time PCR. Virus was consistently detected by real-time PCR and virus isolation at high levels in skin nodules indicating LSDV has a tropism for skin. In contrast, relatively few lesions were observed systemically. Viral DNA was detected by real-time PCR in skin lesions collected on DPI 42. Cattle developing anti-capripoxvirus antibodies starting at DPI 21 was detected by serum neutralization. The disease in this study varied from mild with few secondary skin nodules to generalized infection of varying severity, and was characterized by morbidity with no mortality.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Vaccines (Basel)
                Vaccines (Basel)
                vaccines
                Vaccines
                MDPI
                2076-393X
                08 May 2021
                May 2021
                : 9
                : 5
                : 473
                Affiliations
                [1 ]Infectious Diseases in Animals, Exotic and Particular Diseases, Sciensano, Groeselenberg 99, B-1180 Brussels, Belgium; Ilse.DeLeeuw@ 123456sciensano.be (I.D.L.); kris.declercq@ 123456sciensano.be (K.D.C.)
                [2 ]Experimental Center Machelen, Sciensano, Kerklaan 68, B-1830 Machelen, Belgium; Laurent.Mostin@ 123456sciensano.be (L.M.); Willem.VanCampe@ 123456sciensano.be (W.V.C.)
                [3 ]EURL for Diseases Caused by Capripox Viruses, Sciensano, Groeselenberg 99, B-1180 Brussels, Belgium; Laetitia.Aerts@ 123456sciensano.be
                [4 ]Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Onderstepoort 0110, South Africa; estelle.venter@ 123456jcu.edu.au
                [5 ]College of Public Health, Medical and Veterinary Sciences, Discipline: Veterinary Science, James Cook University, Townsville, QLD 4811, Australia
                [6 ]Institut für Internationale Tiergesundheit/One Health, Friedrich-Loeffler-Institut Federal Research Institute for Animal Health, 17489 Greifswald-Insel Riems, Germany; Eeva.Tuppurainen@ 123456fli.de
                [7 ]Fundamental and Applied Research for Animals & Health (FARAH) Center, Research Unit of Epidemiology and Risk Analysis Applied to Veterinary Sciences (UREAR-ULiège), Faculty of Veterinary Medicine, University of Liege, 4000 Liege, Belgium; claude.saegerman@ 123456uliege.be
                Author notes
                Author information
                https://orcid.org/0000-0003-4056-214X
                https://orcid.org/0000-0001-7351-0827
                https://orcid.org/0000-0001-9087-7436
                https://orcid.org/0000-0002-2928-3521
                Article
                vaccines-09-00473
                10.3390/vaccines9050473
                8151199
                34066658
                40447e93-f23b-4b21-8311-71591a46fb60
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 31 March 2021
                : 03 May 2021
                Categories
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                lumpy skin disease,vaccine evaluation,live attenuated vaccines,lumpy skin disease vaccine

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