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Immune Responses of BALB/c Mice Administrated via Oral Route to a Combined Salmonella Typhimurium Ghost Vaccine

복합 살모넬라 타이피무리움 고스트 백신의 마우스 구강 투여에 의한 면역 응답

  • Kim, Pan Gil (Department of Pharmaceutical Engineering, Gyeongnam National University of Science and Technology) ;
  • Ha, Yeon Jo (Department of Pharmaceutical Engineering, Gyeongnam National University of Science and Technology) ;
  • Lee, Su Man (Department of Pharmaceutical Engineering, Gyeongnam National University of Science and Technology) ;
  • Kim, Sam Woong (Department of Pharmaceutical Engineering, Gyeongnam National University of Science and Technology) ;
  • Gal, Sang Wan (Department of Pharmaceutical Engineering, Gyeongnam National University of Science and Technology)
  • 김판길 (경남과학기술대학교 제약공학과) ;
  • 하연조 (경남과학기술대학교 제약공학과) ;
  • 이수만 (경남과학기술대학교 제약공학과) ;
  • 김삼웅 (경남과학기술대학교 제약공학과) ;
  • 갈상완 (경남과학기술대학교 제약공학과)
  • Received : 2015.06.15
  • Accepted : 2015.10.26
  • Published : 2015.11.30

Abstract

Salmonella Typhimurium (ST) JOL389 and χ3339 are strong virulent strains against mouse. ST χ8554 is derived by deletion of the asd gene from ST χ3339. Plasmid pMMP184 carrying a ghost cassette was transformed into ST χ8554, and ST χ8554 ghost cells were prepared and administrated via the oral route to BALB/c mice. Change in the amount of total IgG was not elicited to boosting of single ST χ8554 ghost cells, but the content was increased from 6 weeks after the 3rd administration. However, when the ST JOL389 ghost cells is administered together with ST χ8554 ghost cells, the content of total IgG was increased in 2 weeks post primary administration. It was found that the content of total IgG of the group mixed with ST JOL389 ghost cells showed an increased value of 8 times or more at 10 weeks when compared with the group of ST χ8554 ghost cells. The content of IgG1, IgG2a, and sIgA in both groups increased from 4 weeks postprimary administration. As a challenge test of virulent ST χ3339, χ8554 (pMMP184) and χ8554 (pMMP184)/JOL389 ghost cell groups showed protection of 50% or more when compared to the control group. These results suggest that the preparation of combined ghost cells from a strong virulent ST increases immunity more than a single strain.

살모넬라 타이피무리움 JOL389와 χ3339는 마우스에 강한 독력을 가진 균주들이며, χ8554는 χ3339로부터 유도되었다. 고스트 카세트를 운반하는 플라스미드 pMMP184가 제조된 후에, BALB/c 마우스의 구강 경로를 경유하여 투여되었다. 총 IgG의 함량 변화는 χ8554 고스트 세포의 부스팅으로 발현 함량이 낮게 나타났지만, 3차 접종의 2주 경과 후, 6주차에서 증가되는 양상을 보였다. 그러나, 혼합 백신 그룹인 JOL389/χ8554 그룹에서는 총 IgG의 함량이 일차 접종 후 2주차부터 상승되는 경향을 보였고, 추가접종이 진행되므로써 많은 상승 폭을 나타내었다. 총 IgG의 함량은 백신 접종 후 10주차에서 χ8554그룹에 비교하여 JOL389/χ8554은 8배 이상 높은 것으로 관찰되었다. IgG1, IgG2a, 분비IgA의 함량은 백신화 후 4주차에서 상승되었다. 독력 살모넬라 타이피무리움 χ3339로 도전실험결과, χ8554 [pMMP184]과 χ8554 [pMMP184]/JOL389은 대조구에 비교하여 50% 이상의 보호효과가 관찰되었다. 이들 결과는 χ8554 [pMMP184]/JOL389은 χ8554 [pMMP184]보다 더 높은 면역 응답을 유도하는 것이 가능한 것으로 추정된다.

Keywords

References

  1. Bertani, G. 1951. Studies on lysogenesis. I. The mode of phage liberation by lysogenic Escherichia coli. J. Bacteriol. 62, 293-300.
  2. Chaudhari, A. A., Jawale, C. V., Kim, S. W. and Lee, J. H. 2012. Construction of a Salmonella Gallinarum ghost as a novel inactivated vaccine candidate and its protective efficacy against fowl typhoid in chickens. Vet. Res. 43, 44-55. https://doi.org/10.1186/1297-9716-43-44
  3. Chaudhari, A. A. and Lee, J. H. 2013. Evaluation of the adjuvant effect of Salmonella-based Escherichia coli heat-labile toxin B subunits on the efficacy of a live Salmonella-delivered avian pathogenic Escherichia coli vaccine. Avian Pathol. 42, 365-372. https://doi.org/10.1080/03079457.2013.811466
  4. DeKruyff, R. H., Rizzo, L. V. and Umetsu, D. T. 1993. Induction of immunoglobulin synthesis by CD4+ T cell clones. Semin. Immunol. 5, 5421-5430.
  5. Gor, D. O., Rose, N. R. and Greenspan, N. S. 2003. Th1-Th2: a procrustean paradigm. Nat. Immunol. 4, 503-505.
  6. Ha, Y. J., Kim, T. W., Kim, S. T., Kang. H. Y., Gal, S. W. and Kim, S. W. 2014a. Ghost vaccine prepared from strong virulent Salmonella typhimurium does not improve immune responses of BALB/c mice. J. Life Sci. 24, 39-45. https://doi.org/10.5352/JLS.2014.24.1.39
  7. Ha, Y. J., Kim, S. T., Kang. H. Y., Gal, S. W. and Kim, S. W. 2014b. The complex Salmonella typhimurium ghost cells play an additional role as an immune adjuvant. J. Life Sci. 24, 154-160. https://doi.org/10.5352/JLS.2014.24.2.154
  8. Jalava, K., Hensel, A., Szostak, M., Resch, S. and Lubitz, W. 2002. Bacterial ghosts as vaccine candidates for veterinary applications. J. Control. Release 85, 17-25. https://doi.org/10.1016/S0168-3659(02)00267-5
  9. Jawale, C. V., Chaudhari, A. A., Jeon, B. W., Nandre, R. M. and Lee, J. H. 2012. Characterization of a novel inactivated Salmonella enterica serovar Enteritidis vaccine candidate generated using a modified cI857/λ PR/gene E expression system. Infect. Immun. 80, 1502-1509. https://doi.org/10.1128/IAI.06264-11
  10. Jechlinger, W., Haller, C., Resch, S., Hofmann, A., Szostak, M. P. and Lubitz, W. 2005. Comparative immunogenicity of the hepatitis B virus core 149 antigen displayed on the inner and outer membrane of bacterial ghosts. Vaccine 23, 3609-3617. https://doi.org/10.1016/j.vaccine.2004.11.078
  11. Jeon, B. W., Nandre, R. M. and Lee, J. H. 2013. Oral immunization with an attenuated Salmonella Gallinarum mutant as a fowl typhoid vaccine with a live adjuvant strain secreting the B subunit of Escherichia coli heat-labile enterotoxin. BMC Vet. Res. 6, 96-104.
  12. Kim, S. W., Kang, H. Y., Hur, J., Gal, S. W., Bang, W. Y., Cho, K. K., Kim, C. W., Bahk, J. D. and Lee, J. H. 2011. Construction of a conditional lethal Salmonella mutant via genetic recombination using the ara system and asd gene. J. Microbiol. Methods 87, 202-207. https://doi.org/10.1016/j.mimet.2011.08.004
  13. Kim, S. W., Moon, K. H., Baik, H. S., Kang, H. Y., Kim, S. K., Bahk, J. D., Hur, J. and Lee, J. H. 2009. Changes of physiological and biochemical properties of Salmonella enterica serovar Typhimurium by deletion of cpxR and lon genes using allelic exchange method. J. Microbiol. Methods 79, 314-320. https://doi.org/10.1016/j.mimet.2009.09.025
  14. Kwon, S. R., Nam, Y. K., Kim, S. K. and Kim, K. H. 2006. Protection of tilapia (Oreochromis mosambicus) from edwardsiellosis by vaccination with Edwardsiella tarda ghosts. Fish Shellfish Immunol. 20, 621-626. https://doi.org/10.1016/j.fsi.2005.08.005
  15. Langemann, T., Koller, V. J., Muhammad, A., Kudela, P., Mayr, U. B. and Lubitz, W. 2010. The Bacterial Ghost platform system: production and applications. Bioeng. Bugs. 1, 326-336. https://doi.org/10.4161/bbug.1.5.12540
  16. Li, Y., Wang, S., Xin, W., Scarpellini, G., Shi, Z., Gunn, B., Roland, K. L. and Curtiss, R. 3rd. 2008. A sopB deletion mutation enhances the immunogenicity and protective efficacy of a heterologous antigen delivered by live attenuated Salmonella enterica vaccines. Infect. Immun. 76, 5238-5246. https://doi.org/10.1128/IAI.00720-08
  17. Mayr, U. B., Haller, C., Haidinger, W., Atrasheuskaya, A., Bukin, E., Lubitz, W. and Ignatyev, G. 2005. Bacterial ghosts as an oral vaccine: a single dose of Escherichia coli O157:H7 bacterial ghosts protects mice against lethal challenge. Infect. Immun. 73, 4810-4817. https://doi.org/10.1128/IAI.73.8.4810-4817.2005
  18. Nandre, R. M., Jawale, C. V. and Lee, J. H. 2013. Enhanced protective immune responses against Salmonella Enteritidis infection by Salmonella secreting an Escherichia coli heat-labile enterotoxin B subunit protein. Comp. Immunol. Microbiol. Infect. Dis. 36, 537-548. https://doi.org/10.1016/j.cimid.2013.06.002
  19. Riedmann, E. M., Kyd, J. M., Cripps, A. W. and Lubitz, W. 2007. Bacterial ghosts as adjuvant particles. Expert. Rev. Vaccines 6, 241-253. https://doi.org/10.1586/14760584.6.2.241
  20. Sambrook, J., Fritsch, E. F. and Maniatis, T. 1989. Molecular Cloning, A Laboratory Manual. 2nd Ed., Cold Spring Harbor Laboratory. Press, Cold Spring Harbor, NY.
  21. Tabrizi, C. A., Walcher, P., Mayr, U. B., Stiedl, T., Binder, M., McGrath, J. and Lubitz, W. 2004. Bacterial ghosts-biological particles as delivery systems for antigens, nucleic acids and drugs. Curr. Opin. Biotechnol. 15, 530-537. https://doi.org/10.1016/j.copbio.2004.10.004