Email this article An Attenuated and Highly Immunogenic Variant of the Vaccinia Virus
- Authors: Shchelkunov S.N.1, Yakubitskiy S.N.1, Titova K.A.1, Pyankov S.A.1, Shulgina I.S.1, Starostina E.V.1, Borgoyakova M.B.1, Kisakov D.N.1, Karpenko L.I.1, Shchelkunova G.A.1, Sergeev A.A.1
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Affiliations:
- State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor
- Issue: Vol 16, No 2 (2024)
- Pages: 82-89
- Section: Research Articles
- Submitted: 10.02.2024
- Accepted: 04.04.2024
- Published: 21.08.2024
- URL: https://actanaturae.ru/2075-8251/article/view/27384
- DOI: https://doi.org/10.32607/actanaturae.27384
- ID: 27384
Cite item
Abstract
The vaccinia virus (VACV) has been used for prophylactic immunization against smallpox for many decades. However, the VACV-based vaccine had been highly reactogenic. Therefore, after the eradication of smallpox, the World Health Organization in 1980 recommended that vaccination against this infection be discontinued. As a result, there has been a rise in the occurrence of orthopoxvirus infections in humans in recent years, with the most severe being the 2022 monkeypox epidemic that reached all continents. Thus, it is crucial to address the pressing matter of developing safe and highly immunogenic vaccines for new generations to combat orthopoxvirus infections. In a previous study, we created a LAD strain by modifying the LIVP (L) VACV strain, which is used as a first-generation smallpox vaccine in Russia. This modification involved introducing mutations in the A34R gene to enhance extracellular virion production and deleting the A35R gene to counteract the antibody response to the viral infection. In this study, a strain LADA was created with an additional deletion in the DNA of the LAD strain ati gene. This ati gene directs the production of a major non-virion immunogen. The findings indicate that the LADA VACV variant exhibits lower levels of reactogenicity in BALB/c mice during intranasal infection, as compared to the original L strain. Following intradermal immunization with a 105 PFU dose, both the LAD and LADA strains were found to induce a significantly enhanced cellular immune response in mice when compared to the L strain. At the same time, the highest level of virus-specific IFN-γ producing cells for the LAD variant was detected on the 7th day post-immunization (dpi), whereas for LADA, it was observed on 14 dpi. The LAD and LADA strains induced significantly elevated levels of VACV-specific IgG compared to the original L strain, particularly between 28 and 56 dpi. The vaccinated mice were intranasally infected with the cowpox virus at a dose of 460 LD50 to assess the protective immunity at 62 dpi. The LADA virus conferred complete protection to mice, with the LAD strain providing 70% protection and the parent strain L offering protection to only 60% of the animals.
About the authors
S. N. Shchelkunov
State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor
Author for correspondence.
Email: snshchel@rambler.ru
Russian Federation, Koltsovo, Novosibirsk region, 630559
S. N. Yakubitskiy
State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor
Email: snshchel@rambler.ru
Russian Federation, Koltsovo, Novosibirsk region, 630559
K. A. Titova
State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor
Email: snshchel@rambler.ru
Russian Federation, Koltsovo, Novosibirsk region, 630559
S. A. Pyankov
State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor
Email: snshchel@rambler.ru
Russian Federation, Koltsovo, Novosibirsk region, 630559
I. S. Shulgina
State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor
Email: snshchel@rambler.ru
Russian Federation, Koltsovo, Novosibirsk region, 630559
E. V. Starostina
State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor
Email: snshchel@rambler.ru
Russian Federation, Koltsovo, Novosibirsk region, 630559
M. B. Borgoyakova
State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor
Email: snshchel@rambler.ru
Russian Federation, Koltsovo, Novosibirsk region, 630559
D. N. Kisakov
State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor
Email: snshchel@rambler.ru
Russian Federation, Koltsovo, Novosibirsk region, 630559
L. I. Karpenko
State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor
Email: snshchel@rambler.ru
Russian Federation, Koltsovo, Novosibirsk region, 630559
G. A. Shchelkunova
State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor
Email: snshchel@rambler.ru
Russian Federation, Koltsovo, Novosibirsk region, 630559
A. A. Sergeev
State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor
Email: snshchel@rambler.ru
Russian Federation, Koltsovo, Novosibirsk region, 630559
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