Generation of an attenuated Tiantan vaccinia virus by deletion of the ribonucleotide reductase large subunit

Generation of an attenuated Tiantan vaccinia virus by deletion of the ribonucleotide reductase... Attenuation of the virulence of vaccinia Tiantan virus (VTT) underlies the strategy adopted for mass vaccination campaigns. This strategy provides advantages of safety and efficacy over traditional vaccines and is aimed at minimization of adverse health effects. In this study, a mutant form of the virus, MVTT was derived from VTT by deletion of the ribonucleotide reductase large subunit (R1) ( TI4L ). Compared to wild-type parental (VTT) and revertant (VTT-rev) viruses, virulence of the mutant MVTT was reduced by 100-fold based on body weight reduction and by 3,200-fold based on determination of the intracranial 50 % lethal infectious dose. However, the immunogenicity of MVTT was equivalent to that of the parental VTT. We also demonstrated that the TI4L gene is not required for efficient replication. These data support the conclusion that MVTT can be used as a replicating virus vector or as a platform for the development of vaccines against infectious diseases and for cancer therapy. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

Generation of an attenuated Tiantan vaccinia virus by deletion of the ribonucleotide reductase large subunit

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Publisher
Springer Vienna
Copyright
Copyright © 2014 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-014-2057-8
Publisher site
See Article on Publisher Site

Abstract

Attenuation of the virulence of vaccinia Tiantan virus (VTT) underlies the strategy adopted for mass vaccination campaigns. This strategy provides advantages of safety and efficacy over traditional vaccines and is aimed at minimization of adverse health effects. In this study, a mutant form of the virus, MVTT was derived from VTT by deletion of the ribonucleotide reductase large subunit (R1) ( TI4L ). Compared to wild-type parental (VTT) and revertant (VTT-rev) viruses, virulence of the mutant MVTT was reduced by 100-fold based on body weight reduction and by 3,200-fold based on determination of the intracranial 50 % lethal infectious dose. However, the immunogenicity of MVTT was equivalent to that of the parental VTT. We also demonstrated that the TI4L gene is not required for efficient replication. These data support the conclusion that MVTT can be used as a replicating virus vector or as a platform for the development of vaccines against infectious diseases and for cancer therapy.

Journal

Archives of VirologySpringer Journals

Published: Sep 1, 2014

References

  • Modified Vaccinia Virus Ankara as antigen delivery system: how can we best use its potential?
    Drexler, I; Staib, C; Sutter, G
  • A vaccinia virus transfer vector using a GUS reporter gene inserted into the I4L locus
    Howley, PM; Spehner, D; Drillien, R
  • The attenuation of vaccinia Tian Tan strain by the removal of the viral M1L-K2L genes
    Zhu, W; Fang, Q; Zhuang, K; Wang, H; Yu, W; Zhou, J; Liu, L; Tien, P; Zhang, L; Chen, Z

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