Clinical Study of Safety and Efficacy of a Polymer-Subunit Adjuvant Influenza Vaccine Applied in Combination with an Immune Modulator in People Aged 60 and Over

Relevance. In Russia, acute respiratory viral infections (ARVI) account for 93% of all infectious diseases. Flu is more serious disease than many ARVI. Flu especially dangerous for people aged 60 years or older, for the reason that they have a weakened immune system, and as a rule there are a chronic diseases. Vaccination is the most effective way to prevent flu. In the Sverdlovsk region of long-term epidemiological monitoring has shown that vaccines can provide protection for up to 92% of persons from some social and age groups. Vaccination of elderly has features because of decline of cellular and humoral immune response to foreign antigens. There is evidence that the addition to the inactivated influenza vaccine immunomodulators immunogenicity of vaccines increased significantly. Goal. To evaluate the effectiveness of the vaccine Grippol® plus with immunomodulator Polyoxidonium® for elderly people aged 60 and older Materials and method. Medical immunobiological drug Grippol® plus -three valency inactivated polymer-subunit influenza vaccine produced by LLC «Scientifically Production Association Petrovax Farm»: 5 microgram hemagglutinin current strains of flu virus subtypes A(H1N1) and A(H3N2) and type B, 500 microgram immunoadjuvant Polioksidonium® in phosphate-salt buffer. The vaccine does not contain a preservative. Polioksidonium® - immunomodulator produced by LLC «Scientifically Production Association Petrovax Farm», which contains as active substance 12 mg Polyoxidonium (azoximer bromide) in a mixture with excipients: mannitol, povidone, betakarotene - up to 18 mg; lactose, potato starch, stearic acid to produce tablets weighing 0.25 g. Placebo - tablet in appearance and packaging are not different from Polioksidonium® produced by LLC «Scientifically Production Association Petrovax Farm» without the active substance and containing potato starch, stearic acid, polyvinylpyrrolidone, lactose monohydrate, betakarotene to obtain tablets with a weight of 0.25 g. Study Design: A prospective open «case - control» randomized placebo-controlled study. Results. Clinical study demonstrated a high safety and areactogenicity profile and immunologic, clinical and epidemiologic efficacy of the Grippol® plus vaccine in people aged 60 and over treated previously with Polyoxidonium® or placebo. Immunogenicity of the vaccine met all the criteria of the Committee for Proprietary Medicinal Products for all three flu virus stains in 21 - 28 days and 6 months after vaccination in both study cohorts. We found no statistically significant differences in the frequency of general and local reactions and immune response rate between the cohorts vaccinated with Grippol® plus with the prior use of Polyoxidonium® or placebo. The incidence rate of acute respiratory viral infections in the age group 60+ immunized with the Grippol® plus vaccine was twice as low as that among the non-vaccinated, p < 0.05.

грипп, пожилые люди, профилактика гриппа вакциной, иммуномодулятор, influenza, elderly people, prevention of influenza with a vaccine, an immune modulator

1. Kurskaya O.G., Sharshov K.A., Alekseev A.Y., Gulyaev M.A., Shestopalov A.M., Shestopalova L.V. et al. The study of local action, acute and chronic forms of syringe inactivated influenza vaccine Ultriks in animal models. Epidemiologiya i Vakcinoprofilaktika [Epidemiology and Vaccinal Prevention]. 2015; 3 (82): 66 – 73 (in Russian).

2. Semenova L.V. Epidemiological features of modern influenza and improving tactics vaccination: Doctorate of med. sci. diss. Perm’; 2012 (in Russian).

3. Clinical recommendations: influenza in adults. Clinical guidelines. Scientific-methodical edition.2014. Available at: http: www.Influenza.spb.ru/files/publications/influenza-adults-clinical-guidelines-2014.pdf (in Russian).

4. Kashirina O.S., Chernikova M.I., Vasilyev Yu.Z. Comparison of the immunogenicity and protective effect of cold-adapted live and inactivated vaccines against influenza type A. Zhurnal Mikrobiologii [Journal of Microbiology]. 2015; 3: 38 – 46 (in Russian) .

5. Saltykov TS Delayed mortality in influenza vaccination and tactics of the infection among the elderly. Epidemiologiya i Vakcinoprofilaktika [Epidemiology and Vaccinal Prevention]. 2008; 2: 55 – 57.

6. Fel’dblyum I.V., Menshikov M.G., Markovic N.I. et al. Prophylactic efficacy of vaccination against pneumococcal disease and influenza-risk patients in the Perm region. Novosti vakcinacii. Vakcinacia (bulleten’) [News vaccination. Vaccination (newsletter)]. 2008; 4 (54): 16 – 18 (in Russian).

7. Popov A.Y., Ezhlova E.B., Melnikov A.A., Frolova N.V., Mikheev V.N., Ryzhikov A.B. et all. Influence of annual immunization against influenza on the incidence of this infection in the Russian Federation. Epidemiologiya i Vakcinoprofilaktika [Epidemiology and Vaccinal Prevention]. 2016; 1 (86): 48 – 56 (in Russian).

8. WHO. Reccommended composition of influenza virus vaccines for use in the 2016 – 2017 Northern hemisphere influenza season. February 2016: 1 – 7.

9. Fel’dblyum I.V., Polushkina A.V., Pavroz K.A., Vorobiev N.N., Isaev N.V., Men’shikov M.G. et al. Evaluation of reactogenicity, safety, and immunogenicity of prophylactic efficacy of domestic split influenza vaccine Grifor. Epidemiologiya i Vakcinoprofilaktika [Epidemiology and Vaccinal Prevention]. 2010; 3 (52): 63 – 67 (in Russian).

10. Romanenko V.V., Briko N.I., Saltykov T.S., Ankudinova A.V., Semenova L.V., Kilyachina A.S. Influence of mass immunization of the population in the process of influenza and acute respiratory viral infections (Sverdlovsk region). Epidemiologiya i Vakcinoprofilaktika [Epidemiology and Vaccinal Prevention]. 2016; 1 (86): 56 – 61 (in Russian).

11. Bektemirov T.A., Gorbunov M.A., Elshina G.A. Prospects of Polyoxidonium with vaccines against viral hepatitis and influenza. Allergia, Astma i Klinicheskaya Immunologia [Allergy, Asthma and Clinical Immunology]. 2001; 1: 63 – 65 (in Russian).

12. Vasiliev Yu.Z. Adjuvants influenza vaccines – the current state. Zhurnal Mikrobiologii [Journal of Microbiology]. 2010; 1: 100 – 110 (in Russian).

13. Burtsev E.I. Specific prevention of influenza in the modern epidemic process: PhD of med. sci. diss. Moscow; 2005 (in Russian).

14. Hendon Yu.Z., Markushin S.G., Vasilyev Yu.M., Akopova I.I., Krivtsov G.G. Improved immunogenicity of the inactivated vaccine of influenza virus strain A/California/7/09 (H1N1) using chitosan as an adjuvant and antigen specificity analysis of influenza virus strain. Zhurnal Virusologii [Journal of Virology]. 2012; 1: 28 – 33 (in Russian).