牛结节性皮肤病疫苗研究进展

doi:10.16431/j.cnki.1671-7236.2021.11.032

摘要/Abstract

摘要： 牛结节性皮肤病可对病畜皮肤造成永久性损害，并会导致产奶量下降、生长发育迟缓、公畜不育和孕畜流产等严重后果，对经济生产具有重要影响。目前尚无治疗该病的特效药，使用安全有效的疫苗是防控该病传播的重要手段。牛结节性皮肤病弱毒活疫苗在许多国家已被成功用于该病的防控，除此之外，由于牛结节性皮肤病病毒与山羊痘病毒及绵羊痘病毒在基因组序列上的高度相似性，山羊痘病毒弱毒活疫苗和绵羊痘病毒弱毒活疫苗在许多地区也被用于该病的防控。牛结节性皮肤病病毒编码基因较多，目前尚未发现基因缺失疫苗和亚单位疫苗具有好的保护效果。近年来灭活疫苗在实验室研究中取得了较大进展，但仍需进一步大规模临床试验以证明其有效性。此外，牛结节性皮肤病病毒作为一种痘病毒，已被证明是表达多种病原微生物抗原的有效载体之一。笔者主要总结了当前牛结节性皮肤病疫苗的研究进展，对弱毒疫苗、灭活疫苗、基因缺失疫苗和亚单位疫苗的使用情况、保护效果及研究方向等方面进行了综述，以期为牛结节性皮肤病疫苗的研发和疫病的防控提供新的思路和见解。

关键词: 牛结节性皮肤病; 羊痘病毒; 疫苗; 载体疫苗

Abstract: Lumpy skin disease causes permanent damage to the skin of infected animals and leads to serious symptoms such as reduction of milk production, growth retardation, infertility of male animals and pre-mature miscarriage of females. As a result, the disease poses an essential threat to economy. Currently, there are no specific antiviral treatments for the disease, and the use of safe and effective vaccine constitutes a major way to prevent and control the spread of the disease. Lumpy skin disease virus attenuated vaccines have been successfully used in the control in many countries. In addition, due to the high similarity of genome sequence in Sheeppox virus, attenuated vaccines of Goatpox virus, Goatpox virus and Sheeppox virus have also been used in the control of Lumpy skin disease virus. Lumpy skin disease virus codes a large number of genes, the current research results have not found that the gene deletion vaccine and subunit vaccine have good protective effect. Inactivated vaccines have shown encouraging results in laboratory studies in recent years, but further large-scale clinical trials are still needed to prove their effectiveness. Finally, as a kind of Poxvirus, Lumpy skin disease virus has been proved to be one of the effective vectors for expressing various pathogenic antigens. This article mainly discussed the current vaccines available for Lumpy skin disease virus, including the application, protection effect, research direction of attenuated vaccines, inactivated vaccines, gene-deleted vaccines, and subunit vaccines, so as to provide novel insights into the development of vaccines and therapeutics for Lumpy skin disease virus in the future.

Key words: lumpy skin disease; Capripoxvirus; vaccine; vector vaccine

中图分类号:

S855.3

谢士杰, 朱俊达, 王天坤, 胡鑫, 魏雯娟, 吴文学, 彭辰. 牛结节性皮肤病疫苗研究进展[J]. 中国畜牧兽医, 2021, 48(11): 4220-4230.

XIE Shijie, ZHU Junda, WANG Tiankun, HU Xin, WEI Wenjuan, WU Wenxue, PENG Chen. Research Progress on Vaccine Development for Lumpy Skin Disease[J]. China Animal Husbandry and Veterinary Medicine, 2021, 48(11): 4220-4230.

参考文献

[1] ALEKSANDR K, OLGA B, DAVID W B, et al. Non-vector-borne transmission of Lumpy skin disease virus[J]. Scientific Reports, 2020, 10(1):7436.
[2] LU G, XIE J, LUO J, et al. Lumpy skin disease outbreaks in China, since 3 August 2019[J]. Trans-boundary and Emerging Diseases, 2021, 68(2):216-219.
[3] WEISS K E.Lumpy Skin Disease Virus[M].Berlin:Springer Berlin Heidelberg, 1968.
[4] MATHIJS E, VANDENBUSSCHE F, HAEGEMAN A, et al. Complete genome sequences of the Neethling-like Lumpy skin disease virus strains obtained directly from three commercial live attenuated vaccines[J]. Genome Announcements, 2016, 4(6):e01255-16.
[5] AGIANNIOTAKI E I, BABIUK S, KATSOULOS P D, et al. Colostrum transfer of neutralizing antibodies against Lumpy skin disease virus from vaccinated cows to their calves[J]. Transboundary and Emerging Diseases, 2018, 65(6):2043-2048.
[6] MANIC M, STOJILJKOVIC M, PETROVIC M, et al. Epizootic features and control measures for lumpy skin disease in South-East Serbia in 2016[J]. Transboundary and Emerging Diseases, 2019, 66(5):2087-2099.
[7] KLEMENT E, BROGLIA A, ANTONIOU S E, et al. Neethling vaccine proved highly effective in controlling lumpy skin disease epidemics in the Balkans[J]. Preventive Veterinary Medicine, 2020, 181:104595.
[8] BEN-GERA J, KLEMENT E, KHINICH E, et al. Comparison of the efficacy of Neethling Lumpy skin disease virus and x10RM65 sheep-pox live attenuated vaccines for the prevention of lumpy skin disease-The results of a randomized controlled field study[J]. Vaccine, 2015, 33(38):4837-4842.
[9] KATSOULOS P D, CHAINTOUTIS S C, DOVAS C I, et al. Investigation on the incidence of adverse reactions, viraemia and haematological changes following field immunization of cattle using a live attenuated vaccine against lumpy skin disease[J]. Transboundary and Emerging Diseases, 2018, 65(1):174-185.
[10] GARI G, ABIE G, GIZAW D, et al. Evaluation of the safety, immunogenicity and efficacy of three capripoxvirus vaccine strains against Lumpy skin disease virus[J]. Vaccine, 2015, 33(28):3256-3261.
[11] TUPPURAINEN E S, BABIUK S, KLEMENT E.Lumpy Skin Disease[M].Berlin:Springer Berlin Heidelberg, 2018.
[12] BYADOVSKAYA O, PESTOVA Y, KONONOV A, et al. Performance of the currently available DIVA Real-time PCR assays in classical and recombinant Lumpy skin disease viruses[J]. Transboundary and Emerging Diseases, 2020, Epub ahead of print.
[13] DAVIES F G, MBUGWA G.The alterations in pathogenicity and immunogenicity of a Kenya sheep and Goat pox virus on serial passage in bovine foetal muscle cell cultures[J]. Journal of Comparative Pathology, 1985, 95(4):565-572.
[14] TUPPURAINEN E S, PEARSON C R, BACHANEK-BANKOWSKA K, et al. Characterization of Sheep pox virus vaccine for cattle against Lumpy skin disease virus[J]. Antiviral Research, 2014, 109(100):1-6.
[15] BRENNER J, BELLAICHE M, GROSS E, et al. Appearance of skin lesions in cattle populations vaccinated against lumpy skin disease:Statutory challenge[J]. Vaccine, 2009, 27(10):1500-1503.
[16] CAPSTICK P B, COACKLEY W.Protection of cattle against lumpy skin disease[J]. Research in Veterinary Science, 1961, 2(4):362-368.
[17] YERUHAM I, PERL S, NYSKA A, et al. Adverse reactions in cattle to a capripox vaccine[J]. Veterinary Record, 1994, 135(14):330-332.
[18] AYELET G, ABATE Y, SISAY T, et al. Lumpy skin disease:Preliminary vaccine efficacy assessment and overview on outbreak impact in dairy cattle at Debre Zeit, Central Ethiopia[J]. Antiviral Research, 2013, 98(2):261-265.
[19] AYELET G, HAFTU R, JEMBERIE S, et al. Lumpy skin disease in cattle in central Ethiopia:Outbreak investigation and isolation and molecular detection of the virus[J]. Revue Scientifique et Technique, 2014, 33(3):877-887.
[20] SALIB F A, OSMAN A H.Incidence of lumpy skin disease among Egyptian cattle in Giza governorate, Egypt[J]. Veterinary World, 2011, 4(4):162-167.
[21] EFSA PANEL ON ANIMAL HEALTH AND WELFARE.Urgent advice on lumpy skin disease[J]. EFSA Journal, 2016, 14(8):e04573.
[22] ABUTARBUSH S M, HANANEH W M, RAMADAN W, et al. Adverse reactions to field vaccination against lumpy skin disease in Jordan[J]. Transboundary and Emerging Diseases, 2016, 63(2):e213-219.
[23] ABDALLAH F M, EL DAMATY H M, KOTB G F.Sporadic cases of lumpy skin disease among cattle in Sharkia province, Egypt:Genetic characterization of Lumpy skin disease virus isolates and pathological findings[J]. Veterinary World, 2018, 11(8):1150-1158.
[24] HAMDI J, BAMOUH Z, JAZOULI M, et al. Experimental evaluation of the cross-protection between Sheeppox and bovine lumpy skin vaccines[J]. Scientific Reports, 2020, 10(1):8888.
[25] SEVIK M, DOGAN M.Epidemiological and molecular studies on lumpy skin disease outbreaks in turkey during 2014-2015[J]. Transboundary and Emerging Diseases, 2017, 64(4):1268-1279.
[26] KONONOV A, BYADOVSKAYA O, KONONOVA S, et al. Detection of vaccine-like strains of Lumpy skin disease virus in outbreaks in Russia in 2017[J]. Archives of Virology, 2019, 164(6):1575-1585.
[27] ZHU Y, LI Y, BAI B, et al. Construction of an attenuated Goatpox virus AV41 strain by deleting the TK gene and ORF8-18[J]. Antiviral Research, 2018, 157:111-119.
[28] 刘昌锦, 邓舜洲, 罗锋, 等.猪痘病毒TK、ORF121、ORF143基因缺失毒株的构建及其生物学特性的测定[J]. 中国畜牧兽医, 2020, 47(3):828-836. LIU C J, DENG S Z, LUO F, et al. Construction of Swinepox virus TK, ORF121 and ORF143 genes deletion strains and determination of their biological characterstics[J]. China Animal Husbandry & Veterinary Medicine, 2020, 47(3):828-836.(in Chinese)
[29] CHERVYAKOVA O V, SULTANKULOVA K T, NISSANOVA R K, et al. Lumpy skin disease virus:Approaches to attenuation for vaccine development[J]. Eurasian Journal of Applied Biotechnology 2019, 1(1):3-14.
[30] BALINSKY C A, DELHON G, AFONSO C L, et al. Sheeppox virus kelch-like gene SPPV-019 affects virus virulence[J]. Journal of Virology, 2007, 81(20):11392-11401.
[31] BOSHRA H, TRUONG T, NFON C, et al. A Lumpy skin disease virus deficient of an IL-10 gene homologue provides protective immunity against virulent Capripoxvirus challenge in sheep and goats[J]. Antiviral Research, 2015, 123:39-49.
[32] KARA P D, MATHER A S, PRETORIUS A, et al. Characterisation of putative immunomodulatory gene knockouts of Lumpy skin disease virus in cattle towards an improved vaccine[J]. Vaccine, 2018, 36(31):4708-4715.
[33] DOUGLASS N, VAN DER WALT A, OMAR R, et al. The complete genome sequence of the Lumpy skin disease virus vaccine Herbivac LS reveals a mutation in the superoxide dismutase gene homolog[J]. Archives of Virology, 2019, 164(12):3107-3109.
[34] MUNYANDUKI H, DOUGLASS N, OFFERMAN K, et al. Influence of the Lumpy skin disease virus (LSDV) superoxide dismutase homologue on host transcriptional activity, apoptosis and histopathology[J]. The Journal of General Virology, 2020, 101(6):645-650.
[35] 李继东, 才学鹏.山羊痘病毒TK基因功能缺失对其增殖的影响[J]. 中国畜牧兽医, 2017, 44(2):319-326. LI J D, CAI X P.Effect on proliferation of goat pox virus of TK gene deficiency[J]. China Animal Husbandry & Veterinary Medicine, 2017, 44(2):319-326.(in Chinese)
[36] SPRYGIN A, PESTOVA Y, BJADOVSKAYA O, et al. Evidence of recombination of vaccine strains of Lumpy skin disease virus with field strains, causing disease[J]. PLoS One, 2020, 15(5):e0232584.
[37] ROUBY S R, BAZID A H, WASFY M, et al. Capripoxviruses:Exploring the genetic relatedness between field and vaccine strains from Egypt[J]. Veterinary World, 2019, 12(12):1924-1930.
[38] SPRYGIN A, BABIN Y, PESTOVA Y, et al. Analysis and insights into recombination signals in Lumpy skin disease virus recovered in the field[J]. PLoS One, 2018, 13(12):e0207480.
[39] BOUMART Z, DAOUAM S, BELKOURATI I, et al. Comparative innocuity and efficacy of live and inactivated sheeppox vaccines[J]. BMC Veterinary Research, 2016, 12(1):133.
[40] HAMDI J, BOUMART Z, DAOUAM S, et al. Development and evaluation of an inactivated lumpy skin disease vaccine for cattle[J]. Veterinary Microbiology, 2020, 245:108689.
[41] WOLFF J, MORITZ T, SCHLOTTAU K, et al. Development of a safe and highly efficient inactivated vaccine candidate against Lumpy skin disease virus[J]. Vaccines, 2020, 9(1):4.
[42] ES-SADEQY Y, BAMOUH Z, ENNAHLI A, et al. Development of an inactivated combined vaccine for protection of cattle against Lumpy skin disease and Bluetongue viruses[J]. Veterinary Microbiology, 2021, 256:109046.
[43] TULMAN E R, AFONSO C L, LU Z, et al. Genome of Lumpy skin disease virus[J]. Journal of Virology, 2001, 75(15):7122-7130.
[44] VENKATESAN G, KUMAR TELI M, SANKAR M, et al. Expression and evaluation of recombinant P32 protein based ELISA for sero-diagnostic potential of capripox in sheep and goats[J]. Molecular and Cellular Probes, 2018, 37:48-54.
[45] TUPPURAINEN E S M, VENTER E H, SHISLER J L, et al. Review:Capripoxvirus diseases:Current status and opportunities for control[J]. Transboundary and Emerging Diseases, 2017, 64(3):729-745.
[46] KUMAR A, YOGISHARADHYA R, VENKATESAN G, et al. Co-administration of recombinant major envelope proteins (rA27L and rH3L) of Buffalopox virus provides enhanced immunogenicity and protective efficacy in animal models[J]. Antiviral Research, 2017, 141:174-178.
[47] HERAUD J M, EDGHILL-SMITH Y, AYALA V, et al. Subunit recombinant vaccine protects against Monkeypox[J]. Journal of Immunology, 2006, 177(4):2552-2564.
[48] XIAO Y, ZENG Y, SCHANTE C, et al. Short-term and longer-term protective immune responses generated by subunit vaccination with smallpox A33, B5, L1 or A27 proteins adjuvanted with aluminum hydroxide and CpG in mice challenged with vaccinia virus[J]. Vaccine, 2020, 38(38):6007-6018.
[49] REEMAN S, GATES A J, PULFORD D J, et al. Protection of mice from lethal vaccinia virus infection by vaccinia virus protein subunits with a CpG adjuvant[J]. Viruses, 2017, 9(12):378.
[50] PARAN N, LUSTIG S, ZVI A, et al. Active vaccination with vaccinia virus A33 protects mice against lethal vaccinia and ectromelia viruses but not against Cowpoxvirus;Elucidation of the specific adaptive immune response[J]. Virology Journal, 2013, 10:229.
[51] SAKHATSKYY P, SHIXIA W, CHUANYOU Z, et al. Immunogenicity and protection efficacy of subunit-based smallpox vaccines using variola major antigens[J]. Virology, 2008, 371:98-107.
[52] CHERVYAKOVA O V, ZAITSEV V L, ISKAKOV B K, et al. Recombinant Sheep pox virus proteins elicit neutralizing antibodies[J]. Viruses, 2016, 8(6):159.
[53] ZHENG M, JIN N, LIU Q, et al. Immunogenicity and protective efficacy of Semliki forest virus replicon-based DNA vaccines encoding Goatpox virus structural proteins[J]. Virology, 2009, 391(1):33-43.
[54] BOSHRA H, TRUONG T, NFON C, et al. Capripoxvirus-vectored vaccines against livestock diseases in Africa[J]. Antiviral Research, 2013, 98(2):217-227.
[55] PROW N A, JIMENEZ MARTINEZ R, HAYBALL J D, et al. Poxvirus-based vector systems and the potential for multi-valent and multi-pathogen vaccines[J]. Expert Review of Vaccines, 2018, 17(10):925-934.
[56] ROMERO C H, BARRETT T, KITCHING R P, et al. Protection of goats against peste des petits ruminants with recombinant Capripoxviruses expressing the fusion and haemagglutinin protein genes of Rinderpest virus[J]. Vaccine, 1995, 13(1):36-40.
[57] ROMERO C H, BARRETT T, CHAMBERLAIN R W, et al. Recombinant Capripoxvirus expressing the hemagglutinin protein gene of Rinderpest virus:Protection of cattle against rinderpest and Lumpy skin disease viruses[J]. Virology, 1994, 204(1):425-429.
[58] NGICHABE C K, WAMWAYI H M, BARRETT T, et al. Trial of a Capripoxvirus-rinderpest recombinant vaccine in African cattle[J]. Epidemiology and Infection, 1997, 118(1):63-70.
[59] DIALLO A, MINET C, BERHE G, et al. Goat immune response to capripox vaccine expressing the hemagglutinin protein of peste des petits ruminants[J]. Annals of the New York Academy of Sciences, 2002, 969:88-91.
[60] BERHE G, MINET C, LE GOFF C, et al. Development of a dual recombinant vaccine to protect small ruminants against Peste-des-petits-ruminants virus and Capripoxvirus infections[J]. Journal of Virology, 2003, 77(2):1571-1577.
[61] WADE-EVANS A M, ROMERO C H, MELLOR P, et al. Expression of the major core structural protein (VP7) of Bluetongue virus, by a recombinant Capripox virus, provides partial protection of sheep against a virulent heterotypic Bluetongue virus challenge[J]. Virology, 1996, 220(1):227-231.
[62] PERRIN A, ALBINA E, BREARD E, et al. Recombinant Capripoxviruses expressing proteins of Bluetongue virus:Evaluation of immune responses and protection in small ruminants[J]. Vaccine, 2007, 25(37-38):6774-6783.
[63] SOI R K, RURANGIRWA F R, MCGUIRE T C, et al. Protection of sheep against Rift Valley fever virus and Sheep poxvirus with a recombinant Capripoxvirus vaccine[J]. Clinical and Vaccine Immunology, 2010, 17(12):1842-1849.
[64] WALLACE D B, ELLIS C E, ESPACH A, et al. Protective immune responses induced by different recombinant vaccine regimes to Rift Valley fever[J]. Vaccine, 2006, 24(49-50):7181-7189.
[65] SUN Z, LIU L, ZHANG H, et al. Expression and functional analysis of Brucella outer membrane protein 25 in recombinant Goat pox virus[J]. Molecular Medicine Reports, 2019, 19(3):2323-2329.
[66] WALLACE D B, VILJOEN G J.Immune responses to recombinants of the South African vaccine strain of Lumpy skin disease virus generated by using thymidine kinase gene insertion[J]. Vaccine, 2005, 23(23):3061-3067.
[67] CÊTRE-SOSSAH C, DICKMU S, KWIATEK O, et al. A G-protein-coupled chemokine receptor:A putative insertion site for a multi-pathogen recombinant Capripoxvirus vaccine strategy[J]. Journal of Immunology Methods, 2017, 448:112-115.
[68] LIU F, ZHANG H, LIU W.Construction of recombinant Capripoxviruses as vaccine vectors for delivering foreign antigens:Methodology and application[J]. Comparative Immunology, Microbiology & Infectious Diseases, 2019, 65:181-188.
[69] ROMERO C H, BARRETT T, EVANS S A, et al. Single Capripoxvirus recombinant vaccine for the protection of cattle against rinderpest and lumpy skin disease[J]. Vaccine, 1993, 11(7):737-742.
[70] AYARI-FAKHFAKH E, DO VALLE T Z, GUILLEMOT L, et al. MBT/Pas mouse:A relevant model for the evaluation of Rift Valley fever vaccines[J]. The Journal of General Virology, 2012, 93(Pt 7):1456-1464.
[71] AYARI-FAKHFAKH E, GHRAM A, ALBINA E, et al. Expression of cytokines following vaccination of goats with a recombinant Capripoxvirus vaccine expressing Rift Valley fever virus proteins[J]. Veterinary Immunology and Immunopathology, 2018, 197:15-20.
[72] CAUFOUR P, RUFAEL T, LAMIEN C E, et al. Protective efficacy of a single immunization with Capripoxvirus-vectored recombinant peste des petits ruminants vaccines in presence of pre-existing immunity[J]. Vaccine, 2014, 32(30):3772-3779.
[73] ASPDEN K, VAN DIJK A A, BINGHAM J, et al. Immunogenicity of a recombinant Lumpy skin disease virus (Neethling vaccine strain) expressing the Rabies virus glycoprotein in cattle[J]. Vaccine, 2002, 20(21-22):2693-2701.
[74] SHEN Y J, SHEPHARD E, DOUGLASS N, et al. A novel candidate HIV vaccine vector based on the replication deficient Capripoxvirus, Lumpy skin disease virus (LSDV)[J]. Virology Journal, 2011, 8:265.
[75] BURGERS W A, GINBOT Z, SHEN Y J, et al. The novel Capripoxvirus vector Lumpy skin disease virus efficiently boosts modified vaccinia Ankara human immunodeficiency virus responses in Rhesus macaques[J]. The Journal of General Virology, 2014, 95(Pt 10):2267-2272.
[76] EUROPEAN FOOD SAFETY AUTHORITY (EFSA), CALISTRI P, DE CLERCQ K, et al. Lumpy skin disease epidemiological report Ⅳ:Data collection and analysis[J]. EFSA Journal, 2020, 18(2):e06010.
[77] EUROPEAN FOOD SAFETY AUTHORITY (EFSA), CALISTRI P, DECLERCQ K, et al. Lumpy skin disease:Ⅲ.Data collection and analysis[J]. EFSA Journal, 2019, 17(3):e05638.
[78] EUROPEAN FOOD SAFETY AUTHORITY (EFSA).Lumpy skin disease Ⅱ.Data collection and analysis[J]. EFSA Journal, 2018, 16(2):e05176.
[79] Lumpy skin disease:Ⅰ.Data collection and analysis[J]. EFSA Journal, 2017, 15(4):e04773.
[80] KITCHING R P.Vaccines for Lumpy skin disease, sheep pox and goat pox[J]. Developments in Biologicals, 2003, 114:161-167.
[81] BABIUK S, BOWDEN T R, BOYLE D B, et al. Capripoxviruses:An emerging worldwide threat to sheep, goats and cattle[J]. Transboundary and Emerging Diseases, 2008, 55(7):263-272.
[82] TUPPURAINEN E S, OURA C A.Review:Lumpy skin disease:An emerging threat to Europe, the Middle East and Asia[J]. Transboundary and Emerging Diseases, 2012, 59(1):40-48.