Журнал микробиологии, эпидемиологии и иммунобиологии. 2020; 97: 564-577
Изучение роли иммунитета к нейраминидазе вируса гриппа в защите от вторичной бактериальной пневмонии, индуцированной S. aureus после гриппозной инфекции у мышей
https://doi.org/10.36233/0372-9311-2020-97-6-7Аннотация
Введение. Пневмония является наиболее частым осложнением после гриппозной инфекции, с которым ассоциированы тяжелые случаи заболеваний и смертельные исходы во время сезонных и пандемических вспышек гриппа. Ранее мы показали, что вакцинирование мышей вирусоподобными частицами (ВПЧ), несущими гемагглютинин (НА) вируса гриппа, снижает смертность, вызванную бактериальными инфекциями после перенесенной гриппозной инфекции у мышей.
Цель данной работы — изучение возможности усиления защитного эффекта ВПЧ при дополнении их нейраминидазой (NA) вируса гриппа.
Материалы и методы. Изучали влияние Gag-ВПЧ, несущих HA или NA вируса гриппа A/Пуэрто-Рико/8/34, отдельно или в комбинации на модели вторичной бактериальной инфекции, индуцированной S. aureus после гриппозной инфекции гомологичным или гетерологичным вакцине вирусами гриппа.
Результаты. Коктейль HA-Gag-ВПЧ 100 нг + NA-Gag-ВПЧ 20 нг полностью предотвращал смертность, потерю веса и репликацию вируса, а также значительно снижал размножение бактерий в легких животных, зараженных гомологичным вирусом гриппа. Иммунизация этим же коктейлем защищала 60% животных от смертности, снижала потерю их веса и ингибировала размножение патогенов в легких животных с вторичной бактериальной инфекцией S. aureus после гриппозной инфекции гетерологичным вирусом гриппа H1N1, несмотря на отсутствие антител, ингибирующих НА и NA этого вируса.
Заключение. Наши результаты показывают, что парентеральная вакцинация ВПЧ, содержащими НА и NA, может улучшить исход вторичной бактериальной пневмонии, индуцированной S. aureus после гриппа, даже если вирус антигенно отличается от вакцинного штамма. При этом в нашей модели иммунитет к НА вируса гриппа имел превалирующее значение.
Список литературы
1. Joseph C., Togawa Y., Shindo N. Bacterial and viral infections associated with influenza. Influenza Other Respir. Viruses. 2013; (7 Suppl. 2): 105–13. https://doi.org/10.1111/irv.12089.
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9. Shapiro A., Raman S., Johnson M., Piehl M. Community-acquired MRSA infections in North Carolina children: prevalence, antibiotic sensitivities, and risk factors. N. C. Med. J. 2009; 70(2): 102–7.
10. Dibah S., Arzanlou M., Jannati E., Shapouri R. Prevalence and antimicrobial resistance pattern of methicillin resistant Staphylococcus aureus (MRSA) strains isolated from clinical specimens in Ardabil, Iran. Iran. J. Microbiol. 2014; 6(3): 163–8.
11. McCullers J.A., Rehg J.E. 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(3): 341–50. https://doi.org/10.1086/341462
12. Iverson A.R., Boyd K.L., McAuley J.L., Plano L.R., Hart M.E., McCullers J.A. Influenza virus primes mice for pneumonia from Staphylococcus aureus. J. Infect. Dis. 2011; 203(6): 880–8. https://doi.org/10.1093/infdis/jiq113
13. Mina M.J., Klugman K.P. The role of influenza in the severity and transmission of respiratory bacterial disease. Lancet Respir. Med. 2014; 2(9): 750–63. https://doi.org/10.1016/S2213-2600(14)70131-6
14. Huber V.C., Peltola V., Iverson A.R., McCullers J.A. Contribution of vaccine-induced immunity toward either the HA or the NA component of influenza viruses limits secondary bacterial complications. J. Virol. 2010; 84(8): 4105–8. https://doi.org/10.1128/JVI.02621-09
15. Chaussee M.S., Sandbulte H.R., Schuneman M.J., DePaula F.P., Addengast L.A., Schlenker E.H., et al. C. Inactivated and live, attenuated influenza vaccines protect mice against influenza: Streptococcus pyogenes super-infections. Vaccine. 2011; 29(21): 3773–81. https://doi.org/10.1016/j.vaccine.2011.03.031
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17. Tricco A.C., Chit A., Soobiah C., Hallett D., Meier G., Chen M.H., et al. Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis. BMC Med. 2013; 11: 153. https://doi.org/10.1186/1741-7015-11-153
18. Lang P.O., Mendes A., Socquet J., Assir N., Govind S., Aspinall R. Effectiveness of influenza vaccine in aging and older adults: comprehensive analysis of the evidence. Clin. Interv. Aging. 2012; 7: 55–64. https://doi.org/10.2147/CIA.S25215
19. Govaert T.M., Thijs C.T., Masurel N., Sprenger M.J., Dinant G.J., Knottnerus J.A. The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial. JAMA. 1994; 272(21): 1661–5.
20. Carrat F., Flahault A. Influenza vaccine: the challenge of antigenic drift. Vaccine. 2007; 25(39-40): 6852–62. https://doi.org/10.1016/j.vaccine.2007.07.027
21. Klausberger M., Leneva I.A., Egorov A., Strobl F., Ghorbanpour S.M., Falynskova I.N., et al. Off-target effects of an insect cell-expressed influenza HA-pseudotyped gag-VLP preparation in limiting postinfluenza Staphylococcus аureus infections. Vaccine. 2019; 38(4): 859–67. https://doi.org/10.1016/j.vaccine.2019.10.083
22. Klausberger M., Leneva I.A., Falynskova I.N., Vasiliev K., Poddubikov A.V., Lindner C., et al. The potential of influenza HA-specific immunity in mitigating lethality of postinfluenza pneumococcal infections. Vaccines. 2019; 7(4): 187. https://doi.org/10.3390/vaccines7040187
23. Leneva I.A., Burtseva E.I., Yatsyshina S.B., Fedyakina I.T., Kirillova E.S., Selkova E.P., et al. Virus susceptibility and clinical effectiveness of anti-influenza drugs during the 2010–2011 influenza season in Russia. 2016. Int. J. Infect. Dis. 2016; 43: 77–84. https://doi.org/10.1016/j.ijid.2016.01.001
24. WHO Manual on Animal Influenza Diagnosis and Surveillance. Available at: https://www.who.int/csr/resources/publications/influenza/whocdscsrncs20025rev.pdf
25. McCullers J.A., Bartmess K.C. Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. J. Infect. Dis. 2003; 187(6): 1000–9. https://doi.org/10.1086/368163
26. Alymova I.V., Samarasinghe A., Vogel P., Green A.M., Weinlich R., McCullers J.A. A novel cytotoxic sequence contributes to influenza А viral protein PB1-F2 pathogenicity and predisposition to secondary bacterial infection. J. Virol. 2014; 88(1): 503–15. https://doi.org/10.1128/JVI.01373-13
27. Li N., Ren A., Wang X., Fan X., Zhao Y., Gao G.F., et al. Influenza viral neuraminidase primes bacterial coinfection through TGF-β-mediated expression of host cell receptors. Proc. Natl. Acad. Sci. USA. 2015; 112(1): 238–43. https://doi.org/10.1073/pnas.1414422112
28. Zurli V., Gallotta M., Taccone M., Chiarot E., Brazzoli M., Corrente F., et al. Positive contribution of adjuvanted influenza vaccines to the resolution of bacterial superinfections. J. Infect. Dis. 2016; 213(12): 1876. https://doi.org/10.1093/infdis/jiw048
29. Zens K.D., Chen J.K., Farber D.L. Vaccine-generated lung tissue-resident memory T cells provide heterosubtypic protection to influenza infection. JCI Insight. 2016; 1(10): e85832. https://doi.org/10.1172/jci.insight.85832
Journal of microbiology, epidemiology and immunobiology. 2020; 97: 564-577
The study of neuraminidase immunity in protection against secondary bacterial pneumonia induced by S. aureus after influenza infection in mice
https://doi.org/10.36233/0372-9311-2020-97-6-7Abstract
Introduction. Pneumonia often occurs secondary to influenza infection and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. We previously have shown that vaccination with Virus-like particles (VLPs) containing hemagglutinin (HA) of influenza virus reduces mortality caused by bacterial infections after an influenza infections in mice.
The aim of this work is to study whether this protective effect may be potentiated by supplementing the HA preparation with the influenza neuraminidase (NA).
Materials and methods. We studied the effect of Gag-VLPs with the influenza HA or NA from А/PR/8/34 alone or in combination, in a lethal BALB/c mouse model of S. aureus infection after vaccine-matched or mismatched influenza virus challenge.
Results. A cocktail of HA-Gag and NA-Gag-VLPs fully protected from weight loss, mortality and viral replication and significantly reduced the bacterial burden in the lungs of А/PR/8/34 infected animals. Immunization with this cocktail HA-Gag-VLPs 100 ng + NA-Gag-VLPs 20 ng also protected 60% of animals from mortality associated with secondary bacterial S. aureus infection following a heterologous H1N1 influenza virus challenge, and led to the significant protection from weight loss and pulmonary pathogen replication even in the absence of HA-inhibition and NA-inhibition antibodies.
Conclusion. Our results indicate that influenza vaccination may improve the outcome of a secondary bacterial pneumonia induced by S. aureus after influenza even when the virus is antigenically different from the vaccine strain. At the same time, in our model, the significance of the immunity to influenza virus HA was prevalent.
References
1. Joseph C., Togawa Y., Shindo N. Bacterial and viral infections associated with influenza. Influenza Other Respir. Viruses. 2013; (7 Suppl. 2): 105–13. https://doi.org/10.1111/irv.12089.
2. Metersky M.L., Masterton R.G., Lode H., File T.M., Babinchak T. Epidemiology, microbiology, and treatment considerations for bacterial pneumonia complicating influenza. Int. J. Infect. Dis. 2012; 16(5): e321–31. https://doi.org/10.1016/j.ijid.2012.01.003
3. Metzger D.W., Sun K. Immune dysfunction and bacterial coinfections following influenza. J. Immunol. 2013; 191(5): 2047–52. https://doi.org/10.4049/jimmunol.1301152
4. Morens D.M., Taubenberger J.K., Fauci A.S. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J. Infect. Dis. 2008; 198(7): 962–70. https://doi.org/10.1086/591708
5. Lindsay M.I., Herrmann E.C., Morrow G.W., Brown A.L. Hong Kong influenza: clinical, microbiologic, and pathologic features in 127 cases. JAMA. 1970; 214(10): 1825–32. https://doi.org/10.1001/jama.1970.03180100019004
6. Palacios G., Hornig M., Cisterna D., Savji N., Bussetti A.V., Kapoor V., et al. Streptococcus pneumoniae coinfection is correlated with the severity of H1N1 pandemic influenza. PLoS One. 2009; 4(12): e8540. https://doi.org/10.1371/journal.pone.0008540
7. Randolph A.G., Vaughn F., Sullivan R., Rubinson L., Thompson B.T., Yoon G., et al. Critically ill children during the 20092010 influenza pandemic in the United States. Pediatrics. 2011; 128(6): e1450-8. https://doi.org/0.1542/peds.2011-0774
8. Giersing B.K., Dastgheyb S.S., Modjarrad K., Moorthy V. Status of vaccine research and development of vaccines for Staphylococcus aureus. Vaccine. 2016; 34(26): 2962–6. https://doi.org/10.1016/j.vaccine.2016.03.110
9. Shapiro A., Raman S., Johnson M., Piehl M. Community-acquired MRSA infections in North Carolina children: prevalence, antibiotic sensitivities, and risk factors. N. C. Med. J. 2009; 70(2): 102–7.
10. Dibah S., Arzanlou M., Jannati E., Shapouri R. Prevalence and antimicrobial resistance pattern of methicillin resistant Staphylococcus aureus (MRSA) strains isolated from clinical specimens in Ardabil, Iran. Iran. J. Microbiol. 2014; 6(3): 163–8.
11. McCullers J.A., Rehg J.E. 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(3): 341–50. https://doi.org/10.1086/341462
12. Iverson A.R., Boyd K.L., McAuley J.L., Plano L.R., Hart M.E., McCullers J.A. Influenza virus primes mice for pneumonia from Staphylococcus aureus. J. Infect. Dis. 2011; 203(6): 880–8. https://doi.org/10.1093/infdis/jiq113
13. Mina M.J., Klugman K.P. The role of influenza in the severity and transmission of respiratory bacterial disease. Lancet Respir. Med. 2014; 2(9): 750–63. https://doi.org/10.1016/S2213-2600(14)70131-6
14. Huber V.C., Peltola V., Iverson A.R., McCullers J.A. Contribution of vaccine-induced immunity toward either the HA or the NA component of influenza viruses limits secondary bacterial complications. J. Virol. 2010; 84(8): 4105–8. https://doi.org/10.1128/JVI.02621-09
15. Chaussee M.S., Sandbulte H.R., Schuneman M.J., DePaula F.P., Addengast L.A., Schlenker E.H., et al. C. Inactivated and live, attenuated influenza vaccines protect mice against influenza: Streptococcus pyogenes super-infections. Vaccine. 2011; 29(21): 3773–81. https://doi.org/10.1016/j.vaccine.2011.03.031
16. Okamoto S., Kawabata S., Fujitaka H., Uehira T., Okuno Y., Hamada S. Vaccination with formalin-inactivated influenza vaccine protects mice against lethal influenza Streptococcus pyogenes superinfection. Vaccine. 2004; 22(21-22): 2887–93. https://doi.org/10.1016/j.vaccine.2003.12.024
17. Tricco A.C., Chit A., Soobiah C., Hallett D., Meier G., Chen M.H., et al. Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis. BMC Med. 2013; 11: 153. https://doi.org/10.1186/1741-7015-11-153
18. Lang P.O., Mendes A., Socquet J., Assir N., Govind S., Aspinall R. Effectiveness of influenza vaccine in aging and older adults: comprehensive analysis of the evidence. Clin. Interv. Aging. 2012; 7: 55–64. https://doi.org/10.2147/CIA.S25215
19. Govaert T.M., Thijs C.T., Masurel N., Sprenger M.J., Dinant G.J., Knottnerus J.A. The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial. JAMA. 1994; 272(21): 1661–5.
20. Carrat F., Flahault A. Influenza vaccine: the challenge of antigenic drift. Vaccine. 2007; 25(39-40): 6852–62. https://doi.org/10.1016/j.vaccine.2007.07.027
21. Klausberger M., Leneva I.A., Egorov A., Strobl F., Ghorbanpour S.M., Falynskova I.N., et al. Off-target effects of an insect cell-expressed influenza HA-pseudotyped gag-VLP preparation in limiting postinfluenza Staphylococcus aureus infections. Vaccine. 2019; 38(4): 859–67. https://doi.org/10.1016/j.vaccine.2019.10.083
22. Klausberger M., Leneva I.A., Falynskova I.N., Vasiliev K., Poddubikov A.V., Lindner C., et al. The potential of influenza HA-specific immunity in mitigating lethality of postinfluenza pneumococcal infections. Vaccines. 2019; 7(4): 187. https://doi.org/10.3390/vaccines7040187
23. Leneva I.A., Burtseva E.I., Yatsyshina S.B., Fedyakina I.T., Kirillova E.S., Selkova E.P., et al. Virus susceptibility and clinical effectiveness of anti-influenza drugs during the 2010–2011 influenza season in Russia. 2016. Int. J. Infect. Dis. 2016; 43: 77–84. https://doi.org/10.1016/j.ijid.2016.01.001
24. WHO Manual on Animal Influenza Diagnosis and Surveillance. Available at: https://www.who.int/csr/resources/publications/influenza/whocdscsrncs20025rev.pdf
25. McCullers J.A., Bartmess K.C. Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. J. Infect. Dis. 2003; 187(6): 1000–9. https://doi.org/10.1086/368163
26. Alymova I.V., Samarasinghe A., Vogel P., Green A.M., Weinlich R., McCullers J.A. A novel cytotoxic sequence contributes to influenza A viral protein PB1-F2 pathogenicity and predisposition to secondary bacterial infection. J. Virol. 2014; 88(1): 503–15. https://doi.org/10.1128/JVI.01373-13
27. Li N., Ren A., Wang X., Fan X., Zhao Y., Gao G.F., et al. Influenza viral neuraminidase primes bacterial coinfection through TGF-β-mediated expression of host cell receptors. Proc. Natl. Acad. Sci. USA. 2015; 112(1): 238–43. https://doi.org/10.1073/pnas.1414422112
28. Zurli V., Gallotta M., Taccone M., Chiarot E., Brazzoli M., Corrente F., et al. Positive contribution of adjuvanted influenza vaccines to the resolution of bacterial superinfections. J. Infect. Dis. 2016; 213(12): 1876. https://doi.org/10.1093/infdis/jiw048
29. Zens K.D., Chen J.K., Farber D.L. Vaccine-generated lung tissue-resident memory T cells provide heterosubtypic protection to influenza infection. JCI Insight. 2016; 1(10): e85832. https://doi.org/10.1172/jci.insight.85832
