Route-coupled pathogenicity and immunogenicity of vaccinia virus variant inoculated mice

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Abstract

Vaccinia virus had played a key role in the global smallpox eradication. However, in case of mass vaccination with various Vaccinia virus strains severe side effects were revealed sometimes ending up with lethal outcomes, especially in immunocompromised humans. Hence, in 1980 the World Health Organization recommended to cancel smallpox vaccination after declaring about smallpox eradication. Over the last 40 years, human population virtually lost immunity not only against smallpox, but also against other zoonotic orthopoxvirus infections, such as monkeypox, cowpox, buffalopox, and camelpox. All of them pose a represent increasing threat to human health and heighten a risk of emerging highly contagious viruses due to natural evolution of previous zoonotic orthopoxviruses. In order to prevent development of small outbreaks into spreading epidemics and, thus, to decrease a risk of emergence due to natural evolution of highly pathogenic for humans orthopoxviruses, efforts should be applied to develop safe new generation live vaccines based on Vaccinia virus with target virulence genes inactivation. These strains should be examined in laboratory animal models inoculated via different routes. Currently, Vaccinia virus often becomes attenuated to create live recombinant vaccines due to inserting target DNA sequences into the virus virulence genes resulting in their inactivation. Vaccinia virus strain LIVP used in the Russian Federation as smallpox vaccine as well as derivative attenuated variant LIVP-GFP created by using genetic engineering methods with inactivating its thymidine kinase gene were examined. Such viruses were intracerebrally inoculated into suckling mice at doses of 101 or 102 PFU/animal for neurovirulence assessment. Adult mice were infected intranasally, subcutaneously or intradermally at doses of 107 or 108 PFU/animal and clinical manifestations were analyzed for 14 days. On the 28th day after the onset, blood serum samples were collected from individual mice to measure virus specific antibody level by using ELISA. It was shown that recombinant Vaccinia virus strain LIVP-GFP displayed markedly lowered neurovirulence and pathogenicity for mice as compared to parental LIVP. Finally, intradermal route turned out to demonstrate the most safe and effective profile for immunization with both examined Vaccinia virus strains.

About the authors

S. N. Shchelkunov

State Research Center of Virology and Biotechnology VECTOR

Author for correspondence.
Email: snshchel@vector.nsc.ru
ORCID iD: 0000-0002-6255-9745

Sergei N. Shchelkunov - PhD, MD (Biology), Professor, Head Researcher, Department of Genomic Research, SRC VB VECTOR.

630559, Novosibirsk Region, Koltsovo.

Phone: +7 (903) 939-94-80 (mobile); Fax: +7 (383) 336-74-09

Russian Federation

A. A. Sergeev

State Research Center of Virology and Biotechnology VECTOR

Email: sergeev_ala@vector.nsc.ru

PhD (Biology), Leading Researcher, Department of Microorganisms Collection, SRC VB VECTOR.

630559, Novosibirsk Region, Koltsovo.

Russian Federation

A. S. Kabanov

State Research Center of Virology and Biotechnology VECTOR

Email: kabanov_as@vector.nsc.ru

PhD (Biology), Senior Researcher, Department of Microorganisms Collection, SRC VB VECTOR.

630559, Novosibirsk Region, Koltsovo.

Russian Federation

S. N. Yakubitskyi

State Research Center of Virology and Biotechnology VECTOR

Email: yakubitskiy_sn@vector.nsc.ru

Junior Researcher, Department of Genomic Research, SRC VB VECTOR.

630559, Novosibirsk Region, Koltsovo.

Russian Federation

T. V. Bauer

State Research Center of Virology and Biotechnology VECTOR

Email: bauer_tv@vector.nsc.ru

Junior Researcher, Department of Genomic Research, SRC VB VECTOR.

630559, Novosibirsk Region, Koltsovo.

Russian Federation

S. A. Pyankov

State Research Center of Virology and Biotechnology VECTOR

Email: piankov_sa@vector.nsc.ru

Leading Researcher, Department of Microorganisms Collection, SRC VB VECTOR.

630559, Novosibirsk Region, Koltsovo.

Russian Federation

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Copyright (c) 2020 Shchelkunov S.N., Sergeev A.A., Kabanov A.S., Yakubitskyi S.N., Bauer T.V., Pyankov S.A.

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