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Cyclamen europaeum (Cyclamen purpurascens) extract as adjuvant for nasal immunization of mice with influenza antigens

Abstract

The article describes the first attempt to use the juice and extract of Cyclamen europaeum (Cyclamen purpurascens) tubers as an adjuvant for intranasal immunization of mice with influenza antigens. The concentration of antigens used for immunization was 300 μg/ml for each subtype. The adjuvant was added at the concentration of 10 and 20 mg/ml. Blood serum was studied using the hemagglutination inhibition reaction (HI) and enzyme immunoassay (ELISA). After two immunizations with a dose of 7.5 μg, the maximum inverse titers to the H1/H3/B components in the HI were 320/80/80, respectively. The administration of an intranasal comparator without an adjuvant did not result in seroconversion which can be detected by the HI. The analysis of the blood sera of mice, immunized intranasally by the antigen only, showed no increase in the antibody levels between the first and second injections. For mice immunized intranasally by a preparation containing 10 mg/ml (0.5 mg per 50 μl dose) of adjuvant the ELISA detected a significant growth of antibody levels for all components, and GMT antibody levels were comparable to GMT antibody levels after a single intramuscular injection of 5 μg of each antigen. Despite a significant serum titer dispersion (which the authors explain by the impossibility of ensuring absolute uniformity in administration of 50 μl of substance via the nasal route) the use of the extract as an adjuvant for intranasal immunization of mice with highly concentrated influenza antigens showed a significant humoral response. The level of this response after two immunizations in some animals was comparable to that after intramuscular administration. The obtained data open the possibility of using Cyclamen europaeum tuber extract or its chemical analogues in further studies in guinea pigs, ferrets or other animal models in order to develop an efficacious adjuvant for intranasal immunization.

About the Authors

A. S. Gudymo
State Research Center of Virology and Biotechnology «Vector»
Russian Federation
PhD student, Junior Research Scientist of the Laboratory of Molecular and Cellular Immunologyof the Department of Zoonotic Diseases and Influenza


S. V. Maltsev
State Research Center of Virology and Biotechnology «Vector»
Russian Federation
Research Scientist of the Laboratory of Molecular and Cellular Immunology of the Department of Zoonotic Diseases and Influenza


V. A. Evseenko
State Research Center of Virology and Biotechnology «Vector»
Russian Federation
Head of the Laboratory of Zoonotic Diseases of the Department of Zoonotic Diseases and Influenza. Candidate of Biological Sciences


N. V. Danilchenko
State Research Center of Virology and Biotechnology «Vector»
Russian Federation
Junior Research Scientist of the Laboratory of Serological Test Methods of the Department of Zoonotic Diseases and Influenza


V. Y. Marchenko
State Research Center of Virology and Biotechnology «Vector»
Russian Federation
Head of the Laboratory of Influenza of the Department of Zoonotic Diseases and Influenza. Candidate of Biological Sciences


A. G. Durymanov
State Research Center of Virology and Biotechnology «Vector»
Russian Federation
Senior Research Scientist of the Laboratory of Influenza Serodiagnostics of the Department of Zoonotic Diseases and Influenza


A. B. Ryzhikov
State Research Center of Virology and Biotechnology «Vector»
Russian Federation
Head of the Department of Zoonotic Diseases and Influenza. Candidate of Biological Sciences


References

1. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012; 12(1): 36–44.

2. Darvishian M, Dijkstra F, van Doorn E, Bijlsma MJ, Donker GA, de Lange MM, et al. Influenza vaccine effectiveness in the Netherlands from 2003/2004 through 2013/2014: The importance of circulating influenza virus types and subtypes. PLoS One 2017; 12(1): e0169528.

3. Raymond DD, Stewart SM, Lee J, Ferdman J, Bajic G, Do KT, et al. Influenza immunization elicits antibodies specific for an egg-adapted vaccine strain. Nat Med. 2016; 22(12): 1465–9.

4. Lee J, Boutz DR, Chromikova V, Joyce MG, Vollmers C, Leung K, et al. Molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination. Nat Med. 2016; 22(12): 1456–64.

5. Glück R. Intranasal immunization against influenza. J Aerosol Med. 2002; 15(2): 221–8.

6. Glück U, Gebbers JO, Glück R. Phase 1 evaluation of intranasal virosomal influenza vaccine with and without Escherichia coli heat-labile toxin in adult volunteers. J Virol. 1999; 73(9): 7780–6.

7. Mutsch M, Zhou W, Rhodes P, Bopp M, Chen RT, Linder T, et al. Use of the inactivated intranasal influenza vaccine and the risk of Bell’s palsy in Switzerland. ¹ Engl J Med. 2004; 350(9): 896–903.

8. Augustin JM, Kuzina V, Andersen SB, Bak S. Molecular activities, biosynthesis and evolution of triterpenoid saponins. Phytochemistry 2011; 72(6): 435–57.

9. Vajdy M, Srivastava I, Polo J, Donnelly J, O’Hagan D, Singh M. Mucosal adjuvants and delivery systems for protein-, DNA- and RNA-based vaccines. Immunol Cell Biol. 2004; 82(6): 617–27.

10. Hamouda T, Chepurnov A, Mank N, Knowlton J, Chepurnova T, Myc A, et al. Efficacy, immunogenicity and stability of a novel intranasal nanoemulsion-adjuvanted influenza vaccine in a murine model. Hum Vaccin. 2010; 6(7): 585–94.

11. Ren ST, Zhang XM, Sun PF, Sun LJ, Guo X, Tian T, et al. Intranasal immunization using mannatide as a novel adjuvant for an inactivated influenza vaccine and its adjuvant effect compared with MF59. PLoS One 2017; 12(1): e0169501.

12. Quan FS, Compans RW, Kang SM. Oral vaccination with inactivated influenza vaccine induces cross-protective immunity. Vaccine 2012; 30(2): 180–8.

13. Methods for quality control indicators of immunobiological medical drugs for influenza prophylaxis and diagnostics. Guidelines. ÌÓ 3.3.2.1758 – 03 (approved by Chief State Sanitary Physician of the Russian Federation) (in Russian).

14. World Health Organization (2004) WHO manual on animal influenza diagnosis and surveillance. Available from: https://goo.gl/k1qjv7.

15. Sinuforte®, Farma Mediterrania, S. L., Spain, LS-000026, Russian National register of medical drugs. Available from: https://goo.gl/ 97qYZo (in Russian).


Review

For citations:


Gudymo A.S., Maltsev S.V., Evseenko V.A., Danilchenko N.V., Marchenko V.Y., Durymanov A.G., Ryzhikov A.B. Cyclamen europaeum (Cyclamen purpurascens) extract as adjuvant for nasal immunization of mice with influenza antigens. BIOpreparations. Prevention, Diagnosis, Treatment. 2017;17(4):233-239. (In Russ.)

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ISSN 2221-996X (Print)
ISSN 2619-1156 (Online)