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Effect of NaCl on the Stability of Oncolytic Vaccinia Virus
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  • Journal title : Journal of Life Science
  • Volume 26, Issue 1,  2016, pp.23-33
  • Publisher : Korean Society of Life Science
  • DOI : 10.5352/JLS.2016.26.1.23
 Title & Authors
Effect of NaCl on the Stability of Oncolytic Vaccinia Virus
Kim, Seong-Geun; Ran, Gui Shao; Kwon, Hyuk-Chan; Hwang, Tae-Ho;
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Pexa-Vec (JX-594) is a specific cancer-targeted oncolytic and immunotherapeutic vaccinia virus. The purpose of this study was to develop methods to maximize the stability of Pexa-Vec. In short-term instability testing, viral activity was rapidly decreased both at 4℃ and at room temperature (RT), but it was completely restored after sonication followed by vortex. Long-term stability testing of Pexa-Vec in the following liquid formulations was performed: (A) 30 mM Tris/pH 7.6, (B) 30 mM Tris/pH 8.6, (C) 30 mM Tris/pH 7.6, 150 mM NaCl, 15% sucrose, (D) 30 mM Tris/pH 7.6, 15% sucrose, and (E) 30 mM Tris/pH 8.6, 15% sucrose. Viral activity decreased less than 2 log10 at 4℃, and RT was observed in 3 days in B, while viral activity was not decreased even after 4–8 weeks at 4℃ and at 1 week in RT in A, suggesting that neutral pH may be essential to maintain virus stability. The addition of 15% sucrose into A (D) significantly increased viral stability at −20℃, 4℃, or RT, and it was also observed at pH 8.6 (E). The addition of 150 mM NaCl into D (C) significantly increased viral stability in addition to the sucrose effect at 4℃ or RT. Accordingly, the viral activity in formulation C was maintained for 1.5 years at 4℃, and for 1-2 weeks in RT. In conclusion, we propose that formulation C can provide the most adequate condition for the proper storage of vaccinia oncolytic virus.
Formulation;NaCl;oncolytic virus;stability;viral activity;
 Cited by
Breitbach, C. J., Parato, K., Burke, J., Hwang, T. H., Bell, J. C. and Kirn, D. H. 2015. Pexa-Vec double agent engineered vaccinia: oncolytic and active immunotherapeutic. Curr. Opin. Virol. 13, 49-54. crossref(new window)

Cruz, P. E., Silva, A. C., Roldão, A., Carmo, M., Carrondo, M. J. and Alves, P. M. 2006. Screening of novel excipients for improving the stability of retroviral and adenoviral vectors. Biotechno.l Prog. 22, 568-576. crossref(new window)

Donnelly, O. G., Errington-Mais, F., Prestwich, R., Harrington, K., Pandha, H., Vile, R. and Melcher, A. A. 2012. Recent clinical experience with oncolytic viruses. Curr. Pharm. Biotechnol. 13, 1834-1841. crossref(new window)

Galdiero, F. 1979. Adenovirus aggregation and preservation in extracellular environment. Arch. Virol. 59, 99-105. crossref(new window)

Heo, J., Reid, T., Ruo, L., Breitbach, C. J., Rose, S., Bloomston, M., Cho, M., Lim, H. Y., Chung, H. C., Kim, C. W., Burke, J., Lencioni, R., Hickman, T., Moon, A., Lee, Y. S., Kim, M. K., Daneshmand, M., Dubois, K., Longpre, L., Ngo, M., Rooney, C., Bell, J. C., Rhee, B. G., Patt, R., Hwang, T. H. and Kirn, D. H. 2013. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Nat. Med. 19, 329-336. crossref(new window)

Kaufman, H. L., Kohlhapp, F. J. and Zloza, A. 2015. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev. Drug Discov. 14, 642-662. crossref(new window)

Kim, M. K., Breitbach, C. J., Moon, A., Heo, J., Lee, Y. K., Cho, M., Lee, J. W., Kim, S. G., Kang, D. H., Bell, J. C., Park, B. H., Kirn, D. H. and Hwang, T. H. 2013. Oncolytic and immunotherapeutic vaccinia induces antibody-mediated complement-dependent cancer cell lysis in humans. Sci. Transl. Med. 5, 185ra63 crossref(new window)

Mackett, M., Smith, G. L. and Moss, B. 1982. Vaccinia virus: A selectable eukaryotic cloning and expression vector. Proc. Natl. Acad. Sci. USA 79, 7,415-7,419. crossref(new window)

Park, B. H., Hwang, T., Liu, T. C., Sze, D. Y., Kim, J. S., Kwon, H. C., Oh, S. Y., Han, S. Y., Yoon, J. H., Hong, S. H., Moon, A., Speth, K., Park, C., Ahn, Y. J., Daneshmand, M., Rhee, B. G., Pinedo, H. M., Bell, J. C. and Kirn, D. H. 2008. Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial. Lancet Oncol. 9, 533-542. crossref(new window)

Smith, G. L., Mackett, M. and Moss, B. 1984. Recombinant vaccinia viruses as new live vaccines. Biotechnol. Genet. Eng. Rev. 2, 383-407. crossref(new window)

Verardi, P. H., Titong, A. and Hagen, C. J. 2012. A vaccinia virus renaissance: new vaccine and immunotherapeutic uses after smallpox eradication. Hum. Vaccin. Immunother. 8, 961-970. crossref(new window)