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Yakubitskiy SN, Kolosova IV, Maksyutov RA, et al. Attenuation of Vaccinia Virus. Acta Naturae. 2015;7(4):113-21
Yakubitskiy, S. N., Kolosova, I. V., Maksyutov, R. A., & Shchelkunov, S. N. (2015). Attenuation of Vaccinia Virus. Acta naturae, 7(4), 113-21.
Yakubitskiy, S N, et al. "Attenuation of Vaccinia Virus." Acta naturae vol. 7,4 (2015): 113-21.
Yakubitskiy SN, Kolosova IV, Maksyutov RA, Shchelkunov SN. Attenuation of Vaccinia Virus. Acta Naturae. 2015 Oct-Dec;7(4):113-21. PMID: 26798498; PMCID: PMC4717256.
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Acta Naturae. 2015 Oct-Dec;7(4):113-21.

Attenuation of Vaccinia Virus.

Acta naturae

S N Yakubitskiy, I V Kolosova, R A Maksyutov, S N Shchelkunov

Affiliations

  1. State Research Center of Virology and Biotechnology "Vector", Koltsovo, Novosibirsk region, Russia.
  2. State Research Center of Virology and Biotechnology "Vector", Koltsovo, Novosibirsk region, Russia ; Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia.

PMID: 26798498 PMCID: PMC4717256

Abstract

Since 1980, in the post-smallpox vaccination era the human population has become increasingly susceptible compared to a generation ago to not only the variola (smallpox) virus, but also other zoonotic orthopoxviruses. The need for safer vaccines against orthopoxviruses is even greater now. The Lister vaccine strain (LIVP) of vaccinia virus was used as a parental virus for generating a recombinant 1421ABJCN clone defective in five virulence genes encoding hemagglutinin (A56R), the IFN-γ-binding protein (B8R), thymidine kinase (J2R), the complement-binding protein (C3L), and the Bcl-2-like inhibitor of apoptosis (N1L). We found that disruption of these loci does not affect replication in mammalian cell cultures. The isogenic recombinant strain 1421ABJCN exhibits a reduced inflammatory response and attenuated neurovirulence relative to LIVP. Virus titers of 1421ABJCN were 3 lg lower versus the parent VACV LIVP when administered by the intracerebral route in new-born mice. In a subcutaneous mouse model, 1421ABJCN displayed levels of VACV-neutralizing antibodies comparable to those of LIVP and conferred protective immunity against lethal challenge by the ectromelia virus. The VACV mutant holds promise as a safe live vaccine strain for preventing smallpox and other orthopoxvirus infections.

Keywords: attenuation; protection; vaccine; vaccinia virus; virulence genes

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