Combined immunization with attenuated live influenza vaccine and chimeric pneumococcal recombinant protein improves the outcome of virus-bacterial infection in mice

Autoři: T. Kramskaya aff001;  G. Leontieva aff001;  Yu. Desheva aff002;  K. Grabovskaya aff001;  T. Gupalova aff001;  L. Rudenko aff002;  A. Suvorov aff001
Působiště autorů: Department of Molecular Microbiology, Institute of Experimental Medicine, Saint Petersburg, Russian Federation aff001;  Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russian Federation aff002;  Department of Fundamental Medicine and Medical Technologies, Faculty of Dentistry and Medical Technologies, Saint Petersburg State University, Saint Petersburg, Russian Federation aff003
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222148


Influenza and its bacterial complications are a leading cause of morbidity and mortality worldwide. The effect of combined immunization with live influenza vaccine and recombinant chimeric pneumococcal protein in dual infection caused by influenza H1N1 and S. pneumoniae (serotype 3) has been studied. The combined vaccine consisted of the strain A/California/2009/38 (H1N1) pdm and chimeric recombinant protein PSPF composed of immunodominant fragments of the surface virulence factors of S. pneumoniae—PsaA, PspA, and Shr1875—associated with modified salmonella flagellin. Vaccinated mice were infected with the influenza virus 24 hours before or 24 hours after the onset of pneumococcal infection. The protective effect of combined vaccination was shown on both models of viral-bacterial infection.

Klíčová slova:

Medicine and health sciences – Infectious diseases – Viral diseases – Influenza – Infectious disease control – Vaccines – Viral vaccines – Recombinant vaccines – Bacterial diseases – Pathology and laboratory medicine – Pathogens – H1N1 – Streptococcus – Pneumococcus – Immunology – Public and occupational health – Preventive medicine – Biology and life sciences – Organisms – Viruses – RNA viruses – Orthomyxoviruses – Influenza viruses – Influenza A virus – Bacteria – Microbiology – Medical microbiology – Microbial pathogens – Viral pathogens – Bacterial pathogens – Virology – Vaccination and immunization


1. Loosli CG. Synergism between respiratory viruses and bacteria. Yale J Biol Med. 1968; 40 (5–6): 522–540. 4386279

2. Bello S, Mincholé E, Fandos S, Lasierra AB, Ruiz MA, Simon AL, et al. Inflammatory response in mixed viral-bacterial community-acquired pneumonia. BMC Pulm Med. 2014 Jul 29; 14:123. doi: 10.1186/1471-2466-14-123 25073709

3. Stöhr K. Preventing and treating influenza. BMJ. 2003; 326 (7401): 1223–1224. doi: 10.1136/bmj.326.7401.1223 12791711

4. McCullers JA. Insights into the interaction between influenza virus and pneumococcus. Clin Microbiol Rev. 2006; 19 (3): 571–82. doi: 10.1128/CMR.00058-05 16847087

5. Desheva YA, Leontieva GF, Kramskaya TA, Smolonogina TA, Grabovskaya KB, Kiseleva IV, et al. Evaluation in Mouse Model of Combined Virus-bacterial Vaccine Based on Attenuated Influenza A(H7N3) Virus and the Group B Streptococcus Recombinant Polypeptides. Open Microbiol J. 2016; 10: 168–175. doi: 10.2174/1874285801610010168 27867430

6. Desheva YA, Leontieva GF, Kramskaya TA, Smolonogina TA, Grabovskaya KB, Landgraf GO, et al. Prevention of Influenza A(H7N9) and Bacterial Infections in Mice Using Intranasal Immunization With Live Influenza Vaccine and the Group B Streptococcus Recombinant Polypeptides. Virology (Auckl). 2017; 8: 1178122X17710949. doi: 10.1177/1178122X17710949 28615930

7. Suvorov A, Dukhovlinov I, Leontieva G, Kramskaya T, Koroleva I, Grabovskaya K, et al. Chimeric Protein PSPF, a Potential Vaccine for Prevention Streptococcus pneumonia infections. Vaccines & Vaccination. 2015; 6:6. Available from:

8. Lu X, Tumpey TM, Morken T, Zaki SR, Cox NJ., Katz JM: A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans. Journal of virology. 1999; 73: 5903–5911. 10364342

9. Desheva Y A, G F Leontieva, Smolonogina T A, T A Kramskaya, Grabovskaya K B, L G Rudenko. et al. Immunomodulation and protective properties of combined mucosal vaccine based on attenuated influenza A virus and recombinant group B Streptococcus polypeptides. Infect Dis Ther. 2015; 3 (I.4): 92. doi: 10.4172/2332-0877.C1.006. ISSN: 2332-0877

10. Potter CW. Chronicle of influenza pandemics. In: Nicholson K. G., Webster R. G., and Hay A. J., editors. Textbook of influenza. London, United Kingdom: Blackwell Scientific Publications; 1998. pp. 3–18.

11. Bakaletz LO. Developing animal models for polymicrobial diseases. Nat. Rev. Microbiol. 2004; 2: 552–568. 15197391

12. Louria D, Blumenfeld H, Ellis J, ED Kilbourne, and D Rogers. Studies on influenza in the pandemic of 1957–58. II. Pulmonary complications of influenza. J. Clin. Investig. 1959; 38: 213–265. doi: 10.1172/JCI103791 13620784

13. Qin Z, Yang Y, Wang H, Luo J, Huang X, You J, et al. Role of Autophagy and Apoptosis in the Postinfluenza Bacterial Pneumonia. Biomed Res Int. 2016; 2016: 3801026. doi: 10.1155/2016/3801026 27376082

14. Hedlund J, Christenson B, Lundbergh P, Ortqvist A. Effects of a large-scale intervention with influenza and 23-valent pneumococcal vaccines in elderly people: a 1-year follow-up. Vaccine. 2003; 21:3906–3911. 12922125

15. Levandowski RA, Gerrity TR, and CS Garrard. Modifications of lung clearance mechanisms by acute influenza A infection. J. Lab. Clin. Med. 1985; 106: 428–432. 4045299

16. Park K, LO Bakaletz, Coticchia JM, Lim DJ Effect of influenza A virus on ciliary activity and dye transport function in the chinchilla eustachian tube. Ann. Otol. Rhinol. Laryngol. 1993; 102: 551–558.

17. Madhi SA, Schoub B, Klugman KP. Interaction between influenza virus and Streptococcus pneumoniae in severe pneumonia. Expert Rev Respir Med. 2008; 2: 663–672. doi: 10.1586/17476348.2.5.663 20477301

18. Loosli CG, SF Stinson, DP Ryan, Hertweck MS, JD Hardy, Serebrin R The destruction of type 2 pneumocytes by airborne influenza PR8-A virus; its effect on surfactant and lecithin content of the pneumonic lesions of mice. Chest. 1975; 67: 7S–14S. 1172777

19. McCullers JA, and KC Bartmess. Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. J. Infect. Dis. 2003; 187: 1000–1009. 12660947

20. McCullers JA, JE Rehg. Lethal synergism between influenza virus and Streptococcus pneumoniae: characterization of a mouse model and the role of platelet-activating factor receptor. J. Infect. Dis. 2002; 186: 341–350. 12134230

21. Plotkowski MC, Bajolet-Laudinat O, Puchelle E. Cellular and molecular mechanisms of bacterial adhesion to respiratory mucosa. Eur.Respir. J. 1993; 6: 903–916. 8339812

22. de Bentzmann S, Plotkowski C, Puchelle E.. Receptors in the Pseudomonas aeruginosa adherence to injured and repairing airway epithelium. Am. J. Respir. Crit. Care Med. 1996; 154: S155–S162. 8876535

23. Hayden FG, Fritz R, MC Lobo, Alvord W, Strober W, SE Straus. Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense. J. Clin. Investig. 1998; 101: 643–649. doi: 10.1172/JCI1355 9449698

24. Julkunen I, Sareneva T, Pirhonen J, Ronni T, Melen K, Matikainen S. Molecular pathogenesis of influenza A virus infection and virus-induced regulation of cytokine gene expression. Cytokine Growth Factor Rev. 2001; 12: 171–180. 11325600

25. Bergeron Y, Ouellet N, AM Deslauriers, Simard M, Olivier M, MG Bergeron. Cytokine kinetics and other host factors in response to pneumococcal pulmonary infection in mice. Infect. Immun. 1998; 66:912–922. 9488375

26. McNamee LA, Harmsen AG. Both influenza-induced neutrophil dysfunction and neutrophil-independent mechanisms contribute to increased susceptibility to a secondary Streptococcus pneumoniae infection. Infect Immun. 2006; 74(12): 6707–6721. doi: 10.1128/IAI.00789-06 16982840

27. Stegemann-Koniszewski S, Gereke M, Orrskog S, Lienenklaus S, Pasche B, Bader SR, et al. TLR7 contributes to the rapid progression but not to the overall fatal outcome of secondary pneumococcal disease following influenza A virus infection. J Innate Immun 2013; 5: 84–96. J. of innate immunity, 2012. 23154432

28. Lee N, Leo YS, Cao B, Chan PK, Kyaw WM, Uyeki TM, et al. Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients. EurRespir J. 2015; 45(6): 1642–52. doi: 10.1183/09031936.00169714 25573405

29. Clements DA, Langdon L, Bland C, Walter E. Influenza A vaccine decreases the incidence of otitis media in 6- to 30-month-old children in day care. Arch. Pediatr. Adolesc. Med. 1995; 149: 1113–1117. 7550814

30. Christenson B, Lundbergh P, Hedlund J, Ortqvist A. Effects of a large-scale intervention with influenza and 23-valent pneumococcal vaccines in adults aged 65 years or older: a prospective study. Lancet. 2001; 357: 1008–1011. 11293594

31. Desheva YA, Leontieva GF, Kramskaya TA, Landgraf GO, Sychev IA, Rekstin AR, et al. Factors of early protective action of live influenza vaccine combined with recombinant bacterial polypeptides against homologous and heterologous influenza infection. Heliyon. 2019; 5(2):e01154. doi: 10.1016/j.heliyon.2019.e01154 30839941

32. Laiño J, Villena J, Suvorov A, Zelaya H, Ortiz Moyano R, Salva S, et al. Nasal immunization with recombinant chimeric pneumococcal protein and cell wall from immunobiotic bacteria improve resistance of infant mice to Streptococcus pneumoniae infection. PLoS One. 2018; 13 (11): e0206661. doi: 10.1371/journal.pone.0206661 30395582

33. Rudd JM, Ashar HK, Chow VT, Teluguakula N. Lethal Synergism between Influenza and Streptococcus pneumoniae. J Infect Pulm Dis. 2016; 2(2): doi: 10.16966/2470-3176.114 27981251

34. Evlashev AYu Meringova LF, Leonteva GF Kramskaya TA, Dukhin AI Grabovskaya KB, et al. Influenza A-group B streptococcal mixed infection. Study of systemic humoral immunity. AdvExp Med Biol. 1997; 418:949–952. No abstract available. 9331807

35. Chetverikova LK, Frolov BA, Kramskaya TA, Polyak RYa. Experimental influenza infection: influence of stress. ActaVirol. 1987; 31(5): 424–33. 2446485

36. Coelingh K, Olajide IR, MacDonald, Yogev R Efficacy and effectiveness of live attenuated influenza vaccine in school-age children. Expert review of vaccines. 2015; 14(10): 1331–1346. doi: 10.1586/14760584.2015.1078732 26372891

37. Karlström A, Boyd KL, English BK, McCullers JA. Treatment with protein synthesis inhibitors improves outcomes of secondary bacterial pneumonia after influenza. J Infect Dis. 2009; 199(3): 311–319. doi: 10.1086/596051 19113989

38. Henderson B M Wilson. Cytokine induction by bacteria: beyond lipopolysaccharide. Cytokine.1996; 8: 269–282. 9162215

39. Magda S. Jonczyk, Michelle Simon, Saumya Kumar, Vitor E. Fernandes, Nicolas Sylvius, Ann-Marie Mallon, et al. Genetic Factors Regulating Lung Vasculature and Immune Cell Functions Associate with Resistance to Pneumococcal Infection. PLoS One. 2014 Mar 3; 9 (3): e89831. doi: 10.1371/journal.pone.0089831 24594938

Článek vyšel v časopise


2019 Číslo 9

Nejčtenější v tomto čísle

Tomuto tématu se dále věnují…


Zvyšte si kvalifikaci online z pohodlí domova

Antiseptika a prevence ve stomatologii
nový kurz
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Citikolin v neuroprotekci a neuroregeneraci: od výzkumu do klinické praxe nejen očních lékařů
Autoři: MUDr. Petr Výborný, CSc., FEBO

Zánětlivá bolest zad a axiální spondylartritida – Diagnostika a referenční strategie
Autoři: MUDr. Monika Gregová, Ph.D., MUDr. Kristýna Bubová

Diagnostika a léčba deprese pro ambulantní praxi
Autoři: MUDr. Jan Hubeňák, Ph.D

Význam nemocničního alert systému v době SARS-CoV-2
Autoři: doc. MUDr. Helena Lahoda Brodská, Ph.D., prim. MUDr. Václava Adámková

Všechny kurzy