Assessing immunogenicity and protectiveness of the vaccinia virus LIVP-GFP in three laboratory animal models

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Abstract

Smallpox eradication and lack of adequate animal model for smallpox infection underlies a necessity to assess immunogenic and protective properties of genetic engineering-created live attenuated smallpox vaccines in several animal models of orthopoxviral infections. Here we compared immunogenic and protective properties of the recombinant vaccinia virus (VACV) LIVP-GFP intradermally (i.d.) inoculated to mice, guinea pigs and rabbits. LIVP-GFP immunization in all animal species was applied at dose of 2 × 104 or 2 × 106 PFU. Control animals were injected with saline. Blood sampling was performed on day 28 after virus LIVP-GFP or saline inoculation. Blood samples were taken intravitally from the retro-orbital venous sinus in mice, heart in guinea pigs or marginal ear vein in rabbits. Serum samples were isolated by precipitating blood cells via centrifugation. The serum anti-VACV IgG titers were determined by ELISA. On day 30 post-immunization animals were intranasally challenged with lethal dose of host specific orthopoxvirus species. Mice were infected by cowpox virus (CPXV) strain GRI-90 at dose 68 LD50, guinea pigs – by VACV GPA at dose 56 LD50, rabbits — by VACV HB-92 at dose 100 LD50. All animals in control group died afterwards, whereas all animals immunized by attenuated recombinant virus LIVP-GFP at dose 2 × 106 PFU survived. In case of the LIVP-GFP immunization at dose 2 × 104 PFU, 88% of mice, 67% of rabbits and 50% of guinea pigs survived after being challenged with species-specific CPXV, VACV HB-92, and VACV GPA. ELISA data for the blood serum samples revealed a correlation between level of VACV-specific antibodies and level of protection in animal species. Based on the data obtained, it could be concluded that all three “animal–orthopoxvirus” models allow to provide with a proper evaluation of immunogenicity and protectiveness for generated modern attenuated vaccines against smallpox and other orthopoxviral human infections. Upon that, it was shown that BALB/c mouse strain was the most convenient investigational host species.

About the authors

S. N. Shchelkunov

State Research Center of Virology and Biotechnology “Vector”, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Author for correspondence.
Email: snshchel@rambler.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. Fax: +7 383 336-74-09.

Russian Federation

A. A. Sergeev

State Research Center of Virology and Biotechnology “Vector”, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Email: sergeev_ala@vector.nsc.ru

PhD (Biology), Leading 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”, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Email: yakubitskiy_sn@vector.nsc.ru

Junior Researcher, Department of Genomic Research, SRC VB “Vector”.

630559, Novosibirsk Region, Koltsovo.

Russian Federation

K. A. Titova

State Research Center of Virology and Biotechnology “Vector”, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Email: snshchel@vector.nsc.ru

Junior Researcher, Department of Microorganisms Collection, SRC VB “Vector”.

630559, Novosibirsk Region, Koltsovo.

Russian Federation

S. A. Pyankov

State Research Center of Virology and Biotechnology “Vector”, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing

Email: pyankov_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) 2021 Shchelkunov S.N., Sergeev A.A., Yakubitskyi S.N., Titova K.A., Pyankov S.A.

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