Skip to main content
PMC home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2020 Mar 1;63(5):623–634. doi: 10.1007/s11427-020-1657-9

A seven-gene-deleted African swine fever virus is safe and effective as a live attenuated vaccine in pigs

Weiye Chen 1,#, Dongming Zhao 1,#, Xijun He 2,#, Renqiang Liu 1,#, Zilong Wang 1,#, Xianfeng Zhang 2, Fang Li 1, Dan Shan 1, Hefeng Chen 1, Jiwen Zhang 1, Lulu Wang 1, Zhiyuan Wen 1, Xijun Wang 1, Yuntao Guan 2, Jinxiong Liu 1, Zhigao Bu 1,2,✉
PMCID: PMC7223596  PMID: 32124180

Abstract

African swine fever (ASF) is a devastating infectious disease in swine that is severely threatening the global pig industry. An efficacious vaccine is urgently required. Here, we used the Chinese ASFV HLJ/18 as a backbone and generated a series of gene-deleted viruses. The virulence, immunogenicity, safety, and protective efficacy evaluation in specific-pathogen-free pigs, commercial pigs, and pregnant sows indicated that one virus, namely HLJ/18-7GD, which has seven genes deleted, is fully attenuated in pigs, cannot convert to the virulent strain, and provides complete protection of pigs against lethal ASFV challenge. Our study shows that HLJ/-18-7GD is a safe and effective vaccine against ASFV, and as such is expected to play an important role in controlling the spread of ASFV.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s11427-020-1657-9 and is accessible for authorized users.

Keywords: African swine fever, vaccine, safety, protective efficacy, pig

Electronic supplementary material

Supplementary materials (264.7KB, pdf)

Acknowledgements

We thank Susan Watson for editing the manuscript. This work was supported by the National Key R&D Program of China (2018YFC1200601), Applied Technology Research and Development Project of Heilongjiang Province (GA19B301), Key-Area Research and Development Program of Guangdong Province (2019B020211004), and the grant from the State Key Laboratory of Veterinary Biotechnology Program (SKLVBP201801).

Compliance and ethics The author(s) declare that they have no conflict of interest.

Footnotes

Contributed equally to this work

References

  1. Alejo A, Matamoros T, Guerra M, Andrés G. A proteomic atlas of the African swine fever virus particle. J Virol. 2018;92:pii. doi: 10.1128/JVI.01293-18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arias M, de la Torre A, Dixon L, Gallardo C, Jori F, Laddomada A, Martins C, Parkhouse RM, Revilla Y, Rodriguez FJM, et al. Approaches and perspectives for development of African swine fever virus vaccines. Vaccines. 2017;5:35. doi: 10.3390/vaccines5040035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Borca MV, Ramirez-Medina E, Silva E, Vuono E, Rai A, Pruitt S, Holinka LG, Velazquez-Salinas L, Zhu J, Gladue DP. J Virol. 2020. Development of a highly effective African swine fever virus vaccine by deletion of the I177L gene results in sterile immunity against the current epidemic Eurasia strain. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Borca MV, O’Donnell V, Holinka LG, Risatti GR, Ramirez-Medina E, Vuono EA, Shi J, Pruitt S, Rai A, Silva E, et al. Deletion of CD2-like gene from the genome of African swine fever virus strain Georgia does not attenuate virulence in swine. Sci Rep. 2020;10:494. doi: 10.1038/s41598-020-57455-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coggins L, Moulton JE, Colgrove GS. Studies with HINDE attenuated African swine fever virus. Cornell Vet. 1968;4:525–540. [PubMed] [Google Scholar]
  6. Gallardo C, Sánchez EG, Pérez-Núñez D, Nogal M, de León P, Carrascosa L, Nieto R, Soler A, Arias ML, Revilla Y. African swine fever virus (ASFV) protection mediated by NH/ P68 and NH/P68 recombinant live-attenuated viruses. Vaccine. 2018;36:2694–2704. doi: 10.1016/j.vaccine.2018.03.040. [DOI] [PubMed] [Google Scholar]
  7. Ge S, Li J, Fan X, Liu F, Li L, Wang Q, Ren W, Bao J, Liu C, Wang H, et al. Molecular characterization of African swine fever virus, China, 2018. Emerg Infect Dis. 2018;24:2131–2133. doi: 10.3201/eid2411.181274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Iglesias I, Rodríguez A, Feliziani F, Rolesu S, de la Torre A. Spatio-temporal analysis of African swine fever in Sardinia (2012–2014): Trends in domestic pigs and wild boar. Transbound Emerg Dis. 2017;64:656–662. doi: 10.1111/tbed.12408. [DOI] [PubMed] [Google Scholar]
  9. Jancovich, J.K., Chapman, D., Hansen, D.T., Robida, M.D., Loskutov, A., Craciunescu, F., Borovkov, A., Kibler, K., Goatley, L., King, K., et al. (2018). Immunization of pigs by DNA prime and recombinant vaccinia virus boost to identify and rank African swine fever virus immunogenic and protective proteins. J Virol 92. [DOI] [PMC free article] [PubMed]
  10. Kim HJ, Cho KH, Lee SK, Kim DY, Nah JJ, Kim HJ, Kim HJ, Hwang JY, Sohn HJ, Choi JG, et al. Transbound Emerg Dis. 2020. Outbreak of African swine fever in South Korea, 2019. [DOI] [PubMed] [Google Scholar]
  11. King DP, Reid SM, Hutchings GH, Grierson SS, Wilkinson PJ, Dixon LK, Bastos ADS, Drew TW. Development of a TaqMan® PCR assay with internal amplification control for the detection of African swine fever virus. J Virol Methods. 2003;107:53–61. doi: 10.1016/S0166-0934(02)00189-1. [DOI] [PubMed] [Google Scholar]
  12. Krug PW, Holinka LG O V, Reese B, Sanford B, Fernandez-Sainz I, Gladue DP, Arzt J, Rodriguez L, Risatti G R, et al. The progressive adaptation of a Georgian isolate of African swine fever virus to vero cells leads to a gradual attenuation of virulence in swine corresponding to major modifications of the viral genome. J Virol. 2015;89:2324–2332. doi: 10.1128/JVI.03250-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Le VP, Jeong DG, Yoon SW, Kwon HM, Trinh TBN, Nguyen T L, Bui TTN, Oh J, Kim JB, Cheong KM, et al. Outbreak of African swine fever, Vietnam, 2019. Emerg Infect Dis. 2019;25:1433–1435. doi: 10.3201/eid2507.190303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Malmquist WA, Hay D. Hemadsorption and cytopathic effect produced by African swine fever virus in swine bone marrow and buffy coat cultures. Am J Vet Res. 1960;21:104–108. [PubMed] [Google Scholar]
  15. Monteagudo PL, Lacasta A, López E, Bosch L, Collado J, Pina-Pedrero S, Correa-Fiz F, Accensi F, Navas MJ, Vidal E, et al. BA71ΔCD2: a new recombinant live attenuated African swine fever virus with cross-protective capabilities. J Virol. 2017;91:pii. doi: 10.1128/JVI.01058-17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Murgia MV, Mogler M, Certoma A, Green D, Monaghan P, Williams DT, Rowland RRR, Gaudreault NN. Evaluation of an African swine fever (ASF) vaccine strategy incorporating priming with an alphavirus-expressed antigen followed by boosting with attenuated ASF virus. Arch Virol. 2019;164:359–370. doi: 10.1007/s00705-018-4071-8. [DOI] [PubMed] [Google Scholar]
  17. O’Donnell V, Holinka LG, Gladue DP, Sanford B, Krug PW, Lu X, Arzt J, Reese B, Carrillo C, Risatti GR, et al. African swine fever virus Georgia isolate harboring deletions of MGF360 and MGF505 genes is attenuated in swine and confers protection against challenge with virulent parental virus. J Virol. 2015;89:6048–6056. doi: 10.1128/JVI.00554-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. O’Donnell V, Holinka LG, Krug PW, Gladue DP, Carlson J, Sanford B, Alfano M, Kramer E, Lu Z, Arzt J, et al. African swine fever virus Georgia 2007 with a deletion of virulence-associated gene 9GL (B119L), when administered at low doses, leads to virus attenuation in swine and induces an effective protection against homologous challenge. J Virol. 2015;89:8556–8566. doi: 10.1128/JVI.00969-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. O’Donnell V, Risatti GR, Holinka LG, Krug PW, Carlson J, Velazquez-Salinas L, Azzinaro PA, Gladue DP, Borca MV. Simultaneous deletion of the 9GL and UK genes from the African swine fever virus Georgia 2007 isolate offers increased safety and protection against homologous challenge. J Virol. 2017;91:pii. doi: 10.1128/JVI.01760-16. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pejsak Z, Truszczyński M, Niemczuk K, Kozak E, Markowska-Daniel I. Epidemiology of African swine fever in Poland since the detection of the first case. Polish J Vet Sci. 2014;17:665–672. doi: 10.2478/pjvs-2014-0097. [DOI] [PubMed] [Google Scholar]
  21. Quembo CJ, Jori F, Vosloo W, Heath L. Genetic characterization of African swine fever virus isolates from soft ticks at the wildlife/domestic interface in Mozambique and identification of a novel genotype. Transbound Emerg Dis. 2018;65:420–431. doi: 10.1111/tbed.12700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Reed LJ, Muench H. A simple method of estimating fifty percent endpoints. Am J Hyg. 1938;27:493–497. [Google Scholar]
  23. Reis AL, Abrams CC, Goatley LC, Netherton C, Chapman DG, Sanchez-Cordon P, Dixon LK. Deletion of African swine fever virus interferon inhibitors from the genome of a virulent isolate reduces virulence in domestic pigs and induces a protective response. Vaccine. 2016;34:4698–4705. doi: 10.1016/j.vaccine.2016.08.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Reis AL, Goatley LC, Jabbar T, Sanchez-Cordon PJ, Netherton CL, Chapman DAG, Dixon LK. Deletion of the African swine fever virus gene DP148R does not reduce virus replication in culture but reduces virus virulence in pigs and induces high levels of protection against challenge. J Virol. 2017;91:pii. doi: 10.1128/JVI.01428-17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Revilla Y, Perez-Nunez D, Richt J A. African swine fever virus biology and vaccine approaches. Adv Virus Res. 2018;100:41–74. doi: 10.1016/bs.aivir.2017.10.002. [DOI] [PubMed] [Google Scholar]
  26. Ribeiro M, Nunes Petisca JL, Lopez Frazao F, Sobral M. Vaccination contre la pest porcine africaine. Bul Off Internatl Epizoot. 1963;60:921. [Google Scholar]
  27. Sánchez-Vizcaíno JM, Mur L, Martínez-López B. African swine fever (ASF): five years around Europe. Vet Microbiol. 2013;165:45–50. doi: 10.1016/j.vetmic.2012.11.030. [DOI] [PubMed] [Google Scholar]
  28. Sánchez EG, Pérez-Núñez D, Revilla Y. Development of vaccines against African swine fever virus. Virus Res. 2019;265:150–155. doi: 10.1016/j.virusres.2019.03.022. [DOI] [PubMed] [Google Scholar]
  29. Sunwoo SY, Pérez-Núñez D, Morozov I, Sánchez E, Gaudreault N, Trujillo J, Mur L, Nogal M, Madden D, Urbaniak K, et al. DNA-protein vaccination strategy does not protect from challenge with African swine fever virus Armenia 2007 strain. Vaccines. 2019;7:12. doi: 10.3390/vaccines7010012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wade A, Achenbach JE, Gallardo C, Settypalli TBK, Souley A, Djonwe G, Loitsch A, Dauphin G, Ngang JJE, Boyomo O, et al. Genetic characterization of African swine fever virus in Cameroon, 2010–2018. J Microbiol. 2019;57:316–324. doi: 10.1007/s12275-019-8457-4. [DOI] [PubMed] [Google Scholar]
  31. Wang N, Zhao D, Wang J, Zhang Y, Wang M, Gao Y, Li F, Wang J, Bu Z, Rao Z, et al. Architecture of African swine fever virus and implications for viral assembly. Science. 2019;366:640–644. doi: 10.1126/science.aaz1439. [DOI] [PubMed] [Google Scholar]
  32. Wen X, He X, Zhang X, Zhang X, Liu L, Guan Y, Zhang Y, Bu Z. Genome sequences derived from pig and dried, food pig feed samples provide important insights into the transmission of African swine fever virus in China in 2018. Emerg Microb Infect. 2019;8:303–306. doi: 10.1080/22221751.2019.1565915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Zhao D, Liu R, Zhang X, Li F, Wang J, Zhang J, Liu X, Wang L, Zhang J, Wu X, et al. Replication and virulence in pigs of the first African swine fever virus isolated in China. Emerg Microb Infect. 2019;8:438–447. doi: 10.1080/22221751.2019.1590128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Zsak L, Caler E, Lu Z, Kutish GF, Neilan JG, Rock DL. A nonessential African swine fever virus gene UK is a significant virulence determinant in domestic swine. J Virol. 1998;72:1028–1035. doi: 10.1128/JVI.72.2.1028-1035.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary materials (264.7KB, pdf)

Articles from Science China. Life Sciences are provided here courtesy of Nature Publishing Group

RESOURCES