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Efficacy of inactivated variant porcine epidemic diarrhea virus vaccines in growing pigs

  • Lee, Seung Heon (Viral Disease Research Division, Animal and Plant Quarantine Agency, Ministry of Agriculture, Food and Rural Affairs) ;
  • Yang, Dong-Kun (Viral Disease Research Division, Animal and Plant Quarantine Agency, Ministry of Agriculture, Food and Rural Affairs) ;
  • Kim, Ha-Hyun (Viral Disease Research Division, Animal and Plant Quarantine Agency, Ministry of Agriculture, Food and Rural Affairs) ;
  • Cho, In-Soo (Viral Disease Research Division, Animal and Plant Quarantine Agency, Ministry of Agriculture, Food and Rural Affairs)
  • Received : 2017.10.27
  • Accepted : 2017.12.21
  • Published : 2018.01.31

Abstract

Purpose: The first aim of this study was to develop a novel inactivated porcine epidemic diarrhea virus (PEDV) vaccine using the recently isolated Korean PEDV QIAP1401 strain and to evaluate its protective efficacy in growing pigs. The second was to determine the optimum adjuvant formulation of the inactivated PEDV vaccine that induces protection against viral challenge. Materials and Methods: To generate high titers of infectious PEDV, the QIAP1401 isolate was passaged in Vero cells. The experimental vaccines were prepared from a binary ethyleneimine-inactivated QIAP1401 strain passaged sequentially 70 times (QIAP1401-p70), formulated with four commercial adjuvants, and administered twice intramuscularly to growing pigs. Challenge studies using a virulent homologous strain of PEDV QIAP1401-p11, which was passaged 11 times after isolation, were performed to assess protection against disease progression and viral shedding during the 15-day observation period. The vaccine-induced antibody responses were measured in serum samples collected at predetermined time points by indirect enzyme-linked immunosorbent assay and virus neutralization test. Results: The QIAP1401-p70 strain had 42 amino acid (aa) mutations, including a 25 aa deletion, and was selected as the inactivated PEDV vaccine candidate. Although none of the pigs that received the experimental vaccines were completely protected against subsequent viral challenge, they exhibited a significantly higher immune response than did non-vaccinated control pigs. Among the vaccine groups, the highest antibody responses were observed in the pigs that received an oil-based multiphasic water/oil/water (W/O/W) emulsion adjuvanted vaccine, which delayed the onset of clinical symptoms and viral shedding. Conclusion: A novel inactivated PEDV vaccine formulated with a W/O/W emulsion adjuvant was both immunogenic and protective against viral challenge.

Keywords

Acknowledgement

Supported by : Animal and Plant Quarantine Agency

References

  1. Debouck P, Pensaert M. Experimental infection of pigs with a new porcine enteric coronavirus, CV 777. Am J Vet Res 1980;41:219-23.
  2. Pensaert MB, Yeo SG. Porcine epidemic diarrhea. In: Straw BE, Zimmerman JJ, D'Allaire S, Taylor DJ, editors. Disease of swine. 9th ed. Ames, IW: Blackwell Publishing; 2006. p.367-72.
  3. Pijpers A, van Nieuwstadt AP, Terpstra C, Verheijden JH. Porcine epidemic diarrhoea virus as a cause of persistent diarrhoea in a herd of breeding and finishing pigs. Vet Rec 1993;132:129-31. https://doi.org/10.1136/vr.132.6.129
  4. Oldham J. Letter to the editor. Pig Farming 1972;10:72-3.
  5. Pensaert MB, de Bouck P. A new coronavirus-like particle associated with diarrhea in swine. Arch Virol 1978;58:243-7. https://doi.org/10.1007/BF01317606
  6. Lee C. Porcine epidemic diarrhea virus: an emerging and re-emerging epizootic swine virus. Virol J 2015;12:193. https://doi.org/10.1186/s12985-015-0421-2
  7. Song DS, Oh JS, Kang BK, et al. Oral efficacy of Vero cell attenuated porcine epidemic diarrhea virus DR13 strain. Res Vet Sci 2007;82:134-40. https://doi.org/10.1016/j.rvsc.2006.03.007
  8. Saif LJ, Pensaert MP, Sestak K, Yeo SG, Jung K. Coronaviruses. In: Zimmerman JJ, Karriker LA, Ramirez A, Schwartz KJ, Stevenson GW, editors. Diseases of swine. 10th ed. Ames, IW: Wiley-Blackwell; 2012. p.501-24.
  9. Song D, Park B. Porcine epidemic diarrhoea virus: a comprehensive review of molecular epidemiology, diagnosis, and vaccines. Virus Genes 2012;44:167-75. https://doi.org/10.1007/s11262-012-0713-1
  10. Bosch BJ, van der Zee R, de Haan CA, Rottier PJ. The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex. J Virol 2003;77:8801-11. https://doi.org/10.1128/JVI.77.16.8801-8811.2003
  11. Chang SH, Bae JL, Kang TJ, et al. Identification of the epitope region capable of inducing neutralizing antibodies against the porcine epidemic diarrhea virus. Mol Cells 2002;14:295-9.
  12. Gallagher TM, Buchmeier MJ. Coronavirus spike proteins in viral entry and pathogenesis. Virology 2001;279:371-4. https://doi.org/10.1006/viro.2000.0757
  13. Sato T, Takeyama N, Katsumata A, Tuchiya K, Kodama T, Kusanagi K. Mutations in the spike gene of porcine epidemic diarrhea virus associated with growth adaptation in vitro and attenuation of virulence in vivo. Virus Genes 2011;43:72-8. https://doi.org/10.1007/s11262-011-0617-5
  14. Lee S, Lee C. Outbreak-related porcine epidemic diarrhea virus strains similar to US strains, South Korea, 2013. Emerg Infect Dis 2014;20:1223-6. https://doi.org/10.3201/eid2007.140294
  15. Park BK, Song D. Recent outbreaks and emergence of mutants of porcine epidemic diarrhea viruses (PEDV) in Korea. Jpn J Vet Res 2016;64(Suppl 1):S25-32.
  16. Lee DK, Park CK, Kim SH, Lee C. Heterogeneity in spike protein genes of porcine epidemic diarrhea viruses isolated in Korea. Virus Res 2010;149:175-82. https://doi.org/10.1016/j.virusres.2010.01.015
  17. Yang DK, Kim HH, Lee SH, Yoon SS, Park JW, Cho IS. Isolation and characterization of a new porcine epidemic diarrhea virus variant that occurred in Korea in 2014. J Vet Sci 2017 Jul 10 [Epub].
  18. Thompson JD, Higgins DG, Gibson TJ. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 1994;22:4673-80. https://doi.org/10.1093/nar/22.22.4673
  19. Robert X, Gouet P. Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res 2014;42:W320-4. https://doi.org/10.1093/nar/gku316
  20. Song D, Moon H, Kang B. Porcine epidemic diarrhea: a review of current epidemiology and available vaccines. Clin Exp Vaccine Res 2015;4:166-76. https://doi.org/10.7774/cevr.2015.4.2.166
  21. Liu S, Xiao L, Nelson C, Hagedorn CH. A cell culture adapted HCV JFH1 variant that increases viral titers and permits the production of high titer infectious chimeric reporter viruses. PLoS One 2012;7:e44965. https://doi.org/10.1371/journal.pone.0044965
  22. Daemer RJ, Feinstone SM, Gust ID, Purcell RH. Propagation of human hepatitis A virus in African green monkey kidney cell culture: primary isolation and serial passage. Infect Immun 1981;32:388-93.
  23. Collin EA, Anbalagan S, Okda F, Batman R, Nelson E, Hause BM. An inactivated vaccine made from a U.S. field isolate of porcine epidemic disease virus is immunogenic in pigs as demonstrated by a dose-titration. BMC Vet Res 2015;11:62. https://doi.org/10.1186/s12917-015-0357-1
  24. Thiel V, Herold J, Schelle B, Siddell SG. Viral replicase gene products suffice for coronavirus discontinuous transcription. J Virol 2001;75:6676-81. https://doi.org/10.1128/JVI.75.14.6676-6681.2001
  25. Xing N, Guan X, An B, et al. Ultrasensitive detection of porcine epidemic diarrhea virus from fecal samples using functionalized nanoparticles. PLoS One 2016;11:e0167325. https://doi.org/10.1371/journal.pone.0167325
  26. Goede D, Murtaugh MP, Nerem J, Yeske P, Rossow K, Morrison R. Previous infection of sows with a "mild" strain of porcine epidemic diarrhea virus confers protection against infection with a "severe" strain. Vet Microbiol 2015;176:161-4. https://doi.org/10.1016/j.vetmic.2014.12.019
  27. Park ME, Lee SY, Kim RH, et al. Enhanced immune responses of foot-and-mouth disease vaccine using new oil/gel adjuvant mixtures in pigs and goats. Vaccine 2014;32:5221-7. https://doi.org/10.1016/j.vaccine.2014.07.040
  28. Comi G, Freedman MS, Kappos L, et al. Pooled safety and tolerability data from four placebo-controlled teriflunomide studies and extensions. Mult Scler Relat Disord 2016;5:97-104. https://doi.org/10.1016/j.msard.2015.11.006
  29. Ibrahim Eel S, Gamal WM, Hassan AI, Mahdy Sel D, Hegazy AZ, Abdel-Atty MM. Comparative study on the immunopotentiator effect of ISA 201, ISA 61, ISA 50, ISA 206 used in trivalent foot and mouth disease vaccine. Vet World 2015;8:1189-98. https://doi.org/10.14202/vetworld.2015.1189-1198
  30. Bouguyon E, Goncalves E, Shevtsov A, et al. A new adjuvant combined with inactivated influenza enhances specific CD8 T cell response in mice and decreases symptoms in swine upon challenge. Viral Immunol 2015;28:524-31. https://doi.org/10.1089/vim.2014.0149
  31. Aziz-Boaron O, Gleser D, Yadin H, et al. The protective effectiveness of an inactivated bovine ephemeral fever virus vaccine. Vet Microbiol 2014;173:1-8. https://doi.org/10.1016/j.vetmic.2014.06.021
  32. Aucouturier J, Dupuis L, Ganne V. Adjuvants designed for veterinary and human vaccines. Vaccine 2001;19:2666-72. https://doi.org/10.1016/S0264-410X(00)00498-9
  33. Jang SI, Lillehoj HS, Lee SH, et al. Mucosal immunity against Eimeria acervulina infection in broiler chickens following oral immunization with profilin in Montanide adjuvants. Exp Parasitol 2011;129:36-41. https://doi.org/10.1016/j.exppara.2011.05.021
  34. Walders B, Raschke A, Neugebauer M, et al. Blending of a conventional Mycoplasma hyopneumoniae vaccine with a positive marker: tracking of immunised pigs by peptidespecific antibodies raised to the marker component. Res Vet Sci 2005;78:135-41. https://doi.org/10.1016/j.rvsc.2004.07.004
  35. Deville S, Arous JB, Bertrand F, Borisov V, Dupuis L. Efficacy of intranasal and spray delivery of adjuvanted live vaccine against infectious bronchitis virus in experimentally infected poultry. Procedia Vaccinol 2012;6:85-92. https://doi.org/10.1016/j.provac.2012.04.012

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