Preclinical studies of immunogenity, protectivity, and safety of the combined vector vaccine for prevention of the middle east respiratory syndrome
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1. | Title | Title of document | Preclinical studies of immunogenity, protectivity, and safety of the combined vector vaccine for prevention of the middle east respiratory syndrome |
2. | Creator | Author's name, affiliation, country | Inna V. Dolzhikova; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | D. M. Grousova; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | O. V. Zubkova; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | A. I. Tukhvatulin; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | A. V. Kovyrshina; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | N. L. Lubenets; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | T. A. Ozharovskaia; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | O. Popova; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | I. B. Esmagambetov; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | D. V. Shcheblyakov; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | I. M. Evgrafova; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | A. A. Nedorubov; I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences; Россия |
2. | Creator | Author's name, affiliation, country | I. V. Gordeichuk; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences; M.P. Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of the Russian Academy of Sciences; Россия |
2. | Creator | Author's name, affiliation, country | S. A. Gulyaev; M.P. Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of the Russian Academy of Sciences; Россия |
2. | Creator | Author's name, affiliation, country | A. G. Botikov; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | L. V. Panina; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | D. V. Mishin; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | S. Y. Loginova; The 48th Central Research Institute of the Ministry of Defense of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | S. V. Borisevich; The 48th Central Research Institute of the Ministry of Defense of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | P. G/ Deryabin; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | B. S. Naroditsky; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences; Россия |
2. | Creator | Author's name, affiliation, country | D. Y. Logunov; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; Россия |
2. | Creator | Author's name, affiliation, country | A. L. Gintsburg; N.F. Gamaleya National Research Center for Epidemiology and Microbiology of the Ministry of Health of the Russian Federation; I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences; Россия |
3. | Subject | Discipline(s) | |
3. | Subject | Keyword(s) | adenoviral vector; Middle East Respiratory Syndrome (MERS); immunogenicity; safety assessment |
4. | Description | Abstract | The Middle East Respiratory Syndrome (MERS) is an acute inflammatory disease of the respiratory system caused by the MERS-CoV coronavirus. The mortality rate for MERS is about 34.5%. Due to its high mortality rate, the lack of therapeutic and prophylactic agents, and the continuing threat of the spread of MERS beyond its current confines, developing a vaccine is a pressing task, because vaccination would help limit the spread of MERS and reduce its death toll. We have developed a combined vector vaccine for the prevention of MERS based on recombinant human adenovirus serotypes 26 and 5. Studies of its immunogenicity have shown that vaccination of animals (mice and primates) induces a robust humoral immune response that lasts for at least six months. Studies of the cellular immune response in mice after vaccination showed the emergence of a specific CD4+ and CD8+ T cell response. A study of the vaccine protectivity conducted in a model of transgenic mice carrying the human DPP4 receptor gene showed that our vaccination protected 100% of the animals from the lethal infection caused by the MERS-CoV virus (MERS-CoV EMC/2012, 100LD50 per mouse). Studies of the safety and tolerability of the developed vaccine in rodents, rabbits, and primates showed a good safety profile and tolerance in animals; they revealed no contraindications for clinical testing.
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5. | Publisher | Organizing agency, location | Acta Naturae Ltd |
6. | Contributor | Sponsor(s) |
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7. | Date | (DD-MM-YYYY) | 27.10.2020 |
8. | Type | Status & genre | Peer-reviewed Article |
8. | Type | Type | Research Article |
9. | Format | File format | |
10. | Identifier | Uniform Resource Identifier | https://actanaturae.ru/2075-8251/article/view/11042 |
10. | Identifier | Digital Object Identifier (DOI) | 10.32607/actanaturae.11042 |
11. | Source | Title; vol., no. (year) | Acta Naturae; Vol 12, No 3 (2020) |
12. | Language | English=en | ru |
13. | Relation | Supp. Files |
Fig. 1. Titers of glycoprotein-specific IgGs in the serum of immunized animals two weeks (A) and four weeks (B) after boosting of the vaccination. The abscissa axis represents immunization doses (v.p. per mouse); the ordinate axis shows reciprocal IgG titers. The geometric mean titers and 95% confidence intervals are indicated (272KB) doi: 10.32607/20758251-2020-12-3-114-123-660 Fig. 2. Titers of glycoprotein-specific IgGs in the serum of immunized animals six months after vaccination. The ordinate axis shows reciprocal IgG titers. The geometric mean titer and the 95% confidence interval (n = 6) are indicated (89KB) doi: 10.32607/20758251-2020-12-3-114-123-661 Fig. 3. A – Titers of glycoprotein-specific IgG in the plasma of immunized marmosets after vaccination. IgG titers are shown on the ordinate axis; time after immunization is represented on the abscissa axis. Individual titers for each studied animal and the geometric mean titer (n = 3) are indicated. B – Titers of virus-neutralizing antibodies in the plasma of immunized marmosets after vaccination. Virus-neutralizing antibody titers are shown on the ordinate axis; time after immunization is represented on the abscissa axis. Individual titers for each studied animal and the geometric mean titer (n = 3) are indicated (207KB) doi: 10.32607/20758251-2020-12-3-114-123-662 Fig. 4. Study of the lymphoproliferative activity of splenocytes in mice immunized with the vaccine or placebo. The levels (in %) of proliferating CD4+ and CD8+ T cells re-stimulated with recombinant MERS-CoV S glycoprotein on the 18th day after vaccination are presented. Medians of the percentage of proliferating cells after re-stimulation and 95% CI for the median for each group (n = 6) are indicated. * – p < 0.05 (116KB) doi: 10.32607/20758251-2020-12-3-114-123-663 Fig. 5. Increase in the concentration of IFN-gamma in the splenocyte media of immunized and non-immunized mice after re-stimulation with recombinant MERS-CoV S glycoprotein. Median increase in the concentration of IFN-gamma after re-stimulation and 95% CI for the median for each group (n = 6) are indicated. * – p < 0.05 (98KB) doi: 10.32607/20758251-2020-12-3-114-123-664 Fig. 6. Survival of vaccinated (n = 10) and non-vaccinated (control group, n = 10) animals after a lethal infection of MERS-CoV. The ordinate axis shows the survival rate of animals (%). The abscissa axis represents time after immunization (days) (141KB) doi: 10.32607/20758251-2020-12-3-114-123-665 Fig. 7. Rectal temperature, body weight, and biochemical blood parameters in primates (common marmosets) immunized with the combined vector vaccine against MERS (indicated by triangles) and control animals (marked by circles) (605KB) doi: 10.32607/20758251-2020-12-3-114-123-666 |
14. | Coverage | Geo-spatial location, chronological period, research sample (gender, age, etc.) | |
15. | Rights | Copyright and permissions |
Copyright (c) 2020 Dolzhikova I.V., Grousova D.M., Zubkova O.V., Tukhvatulin A.I., Kovyrshina A.V., Lubenets N.L., Ozharovskaia T.A., Popova O., Esmagambetov I.B., Shcheblyakov D.V., Evgrafova I.M., Nedorubov A.A., Gordeichuk I.V., Gulyaev S.A., Botikov A.G., Panina L.V., Mishin D.V., Loginova S.Y., Borisevich S.V., Deryabin P.G., Naroditsky B.S., Logunov D.Y., Gintsburg A.L.![]() This work is licensed under a Creative Commons Attribution 4.0 International License. |