Comparative study of the biological properties of influenza А virus mutants obtained by site-specific mutagenesis and the live influenza reassortant vaccine variant
The aim of study was to carry out comparative investigation of biological properties of site-specific mutants of Influenza A virus and variant of live cold-adapted (CA) influenza reassortant vaccine. Materials and methods. The genetic stability of site-specific mutants (SSM) of the A/WSN/33 (H1N1...
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| Format: | Article |
| Language: | Russian |
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Central Research Institute for Epidemiology
2022-12-01
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| Series: | Журнал микробиологии, эпидемиологии и иммунобиологии |
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| Online Access: | https://microbiol.crie.ru/jour/article/viewFile/1165/775 |
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| author | Bogdan S. Cherepovich Artem A. Rtishchev Irina I. Akopova Olga V. Borisova Vladimir Y. Kost Nina M. Kutuzova Stanislav G. Markushin |
| author_facet | Bogdan S. Cherepovich Artem A. Rtishchev Irina I. Akopova Olga V. Borisova Vladimir Y. Kost Nina M. Kutuzova Stanislav G. Markushin |
| author_sort | Bogdan S. Cherepovich |
| collection | DOAJ |
| description | The aim of study was to carry out comparative investigation of biological properties of site-specific mutants of Influenza A virus and variant of live cold-adapted (CA) influenza reassortant vaccine.
Materials and methods. The genetic stability of site-specific mutants (SSM) of the A/WSN/33 (H1N1) strain with ts (temperature sensitive)-mutations in polymerase genes was studied using a stress-test in MadinDarby Canine Kidney (MDCK) culture. A comparative study of immunogenicity of U2 and M26 mutants with the high genetic stability and the CA-reassortant with similar surface proteins was carried out. The increase in the antibody titer was investigated using enzyme-linked immunosorbent assay and the reaction of delayed hemagglutination. Ability of the studied viruses to induce type 1 interferon in A549 cells was determined using real-time polymerase chain reaction (real-time PCR).
Results. It was shown that U2 and M26 mutants, which have 3 ts-mutations or more in polymerase genes have high genetic stability. It was found that U2 and M26 mutants induced a higher antibody titers than the CA reassortant in mice following the intranasal immunization. The ability of site-specific mutants and CA reassortant to induce type 1 interferon was also investigated. Mutants U2 and M26 increased the level of interferon to a greater extent than the CA-reassortant.
Conclusion. The data obtained indicate that SSM U2 and M26 with 3 ts-mutations or more in the genome have a significant level of genetic stability. Mutants U2 and M26 have a higher immunogenicity and a higher ability to induce interferon in comparison with the CA reassortant. These facts allow us to conclude that SSM of the influenza virus with a set of mutations in polymerase genes can be considered as promising candidates for live influenza vaccines. |
| first_indexed | 2024-04-10T20:08:03Z |
| format | Article |
| id | doaj.art-6dccab7a0a0b42209cdd04c58a343699 |
| institution | Directory Open Access Journal |
| issn | 0372-9311 2686-7613 |
| language | Russian |
| last_indexed | 2024-04-10T20:08:03Z |
| publishDate | 2022-12-01 |
| publisher | Central Research Institute for Epidemiology |
| record_format | Article |
| series | Журнал микробиологии, эпидемиологии и иммунобиологии |
| spelling | doaj.art-6dccab7a0a0b42209cdd04c58a3436992023-01-26T15:09:56ZrusCentral Research Institute for EpidemiologyЖурнал микробиологии, эпидемиологии и иммунобиологии0372-93112686-76132022-12-0199555756410.36233/0372-9311-239842Comparative study of the biological properties of influenza А virus mutants obtained by site-specific mutagenesis and the live influenza reassortant vaccine variantBogdan S. Cherepovich0https://orcid.org/0000-0002-5803-6263Artem A. Rtishchev1https://orcid.org/0000-0002-4212-5093Irina I. Akopova2https://orcid.org/0000-0003-1795-4356Olga V. Borisova3https://orcid.org/0000-0002-7664-2945Vladimir Y. Kost4https://orcid.org/0000-0003-1703-2685Nina M. Kutuzova5https://orcid.org/0000-0002-5963-9525Stanislav G. Markushin6https://orcid.org/0000-0003-0994-5337I. Mechnikov Research Institute for Vaccines and SeraI. Mechnikov Research Institute for Vaccines and SeraI. Mechnikov Research Institute for Vaccines and SeraI. Mechnikov Research Institute for Vaccines and SeraShemyakin and Ovchinnikov Institute of Bioorganic Chemistry RASMoscow State Pedagogical UniversityНаучно-исследовательский институт вакцин и сывороток им. И.И. МечниковаThe aim of study was to carry out comparative investigation of biological properties of site-specific mutants of Influenza A virus and variant of live cold-adapted (CA) influenza reassortant vaccine. Materials and methods. The genetic stability of site-specific mutants (SSM) of the A/WSN/33 (H1N1) strain with ts (temperature sensitive)-mutations in polymerase genes was studied using a stress-test in MadinDarby Canine Kidney (MDCK) culture. A comparative study of immunogenicity of U2 and M26 mutants with the high genetic stability and the CA-reassortant with similar surface proteins was carried out. The increase in the antibody titer was investigated using enzyme-linked immunosorbent assay and the reaction of delayed hemagglutination. Ability of the studied viruses to induce type 1 interferon in A549 cells was determined using real-time polymerase chain reaction (real-time PCR). Results. It was shown that U2 and M26 mutants, which have 3 ts-mutations or more in polymerase genes have high genetic stability. It was found that U2 and M26 mutants induced a higher antibody titers than the CA reassortant in mice following the intranasal immunization. The ability of site-specific mutants and CA reassortant to induce type 1 interferon was also investigated. Mutants U2 and M26 increased the level of interferon to a greater extent than the CA-reassortant. Conclusion. The data obtained indicate that SSM U2 and M26 with 3 ts-mutations or more in the genome have a significant level of genetic stability. Mutants U2 and M26 have a higher immunogenicity and a higher ability to induce interferon in comparison with the CA reassortant. These facts allow us to conclude that SSM of the influenza virus with a set of mutations in polymerase genes can be considered as promising candidates for live influenza vaccines.https://microbiol.crie.ru/jour/article/viewFile/1165/775site-specific mutantsinfluenza virusgenetic stabilityimmunogenicityca-reassortantinterferonogenicitylive influenza vaccines |
| spellingShingle | Bogdan S. Cherepovich Artem A. Rtishchev Irina I. Akopova Olga V. Borisova Vladimir Y. Kost Nina M. Kutuzova Stanislav G. Markushin Comparative study of the biological properties of influenza А virus mutants obtained by site-specific mutagenesis and the live influenza reassortant vaccine variant Журнал микробиологии, эпидемиологии и иммунобиологии site-specific mutants influenza virus genetic stability immunogenicity ca-reassortant interferonogenicity live influenza vaccines |
| title | Comparative study of the biological properties of influenza А virus mutants obtained by site-specific mutagenesis and the live influenza reassortant vaccine variant |
| title_full | Comparative study of the biological properties of influenza А virus mutants obtained by site-specific mutagenesis and the live influenza reassortant vaccine variant |
| title_fullStr | Comparative study of the biological properties of influenza А virus mutants obtained by site-specific mutagenesis and the live influenza reassortant vaccine variant |
| title_full_unstemmed | Comparative study of the biological properties of influenza А virus mutants obtained by site-specific mutagenesis and the live influenza reassortant vaccine variant |
| title_short | Comparative study of the biological properties of influenza А virus mutants obtained by site-specific mutagenesis and the live influenza reassortant vaccine variant |
| title_sort | comparative study of the biological properties of influenza а virus mutants obtained by site specific mutagenesis and the live influenza reassortant vaccine variant |
| topic | site-specific mutants influenza virus genetic stability immunogenicity ca-reassortant interferonogenicity live influenza vaccines |
| url | https://microbiol.crie.ru/jour/article/viewFile/1165/775 |
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