Bacterial lysates: conventional views and a new paradigm
DOI: 10.32364/2618-8430-2021-4-3-284-291
A.L. Zaplatnikov1, A.A. Girina2, V.I. Svintsitskaya1, I.V. Lepiseva3, M.V. Leshik1
1Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation
2Khanty-Mansi State Medical Academy, Khanty-Mansiysk, Russian Federation
3Children’s Republican Hospital, Petrozavodsk, Russian Federation
This paper addresses published data on therapeutic, preventive efficacy, and safety of bacterial lysates (BLs) in pediatric practice. Studies on the mechanisms of action of BLs are discussed. Experimental evidence demonstrates that the preventive effect of BLs is maintained even in the high level of bacterial lysis characterized by the presence of only small peptides or even their fragments without antigenic properties. The authors discuss the potential involvement of BLs in the development of trained immunity, whose effects last less time than a conventional epitope-specific adaptive immune memory. The article provides a pathogenic basis for BL use to prevent and manage recurrent respiratory infections and control respiratory allergic diseases as a part of complex treatment. Our data demonstrate a high efficacy of polyvalent mechanical BL to prevent acute and recurrent respiratory infections in children of organized communities, a reduced rate of bacterial complications, and 20 the rate of antibiotic prescription when using BLs. Good tolerability and the lack of adverse and side effects of BLs are emphasized.
Keywords: bacterial lysates, asthma, children, immunity, immune prophylaxis, polyvalent mechanical bacterial lysate, respiratory infections, recurrent respiratory infections, trained immunity.
For citation: Zaplatnikov A.L., Girina A.A., Svintsitskaya V.I. et al. Bacterial lysates: conventional views and a new paradigm. Russian Journal of Woman and Child Health. 2021;4(3):284–291 (in Russ.). DOI: 10.32364/2618-8430-2021-4-3-284-291.
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35. Markova T.P., Kim M.N., Chuvirova A.G.. Ismigen® in complex treatment of children with bronchial asthma. Pediatria. 2017;96(4):159–165 (in Russ.). DOI: 10.24110/0031-403X-2017-96-4-159-165.
36. Bartkowiak-Emeryk M., Emeryk A., Roliński J. et al. Impact of Polyvalent Mechanical Bacterial Lysate on lymphocyte number and activity in asthmatic children: a randomized controlled trial. Allergy Asthma Clin Immunol. 2021;17(1):10. DOI: 10.1186/s13223-020-00503-4.
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38. Netea M.G., Quintin J., van der Meer J.W. Trained immunity: a memory for innate host defense. Cell Host Microbe. 2011;9:355–361. DOI: 10.1016/j.chom.2011.04.006.
39. Netea M.G., Dominguez-Andres J., Barreiro L.B. et al. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020;20:375–388. DOI: 10.1038/s41577-020-0285-6.
2. Kimberlin D.W., ed. Red Book: 2018–2021. Report of the Committee on Infection Diseases. 31th ed., ed. Itasca, IL: American Academy of Pediatrics, 2018.
3. Zaplatnikov A.L., Girina A.A., Gluhareva N.S. et al. Immunoprophylaxis of acute respiratory infections: routine practice and new opportunities. Lechaschi Vrach. 2015;4:51–55 (in Russ.).
4. Jara-Perez J.V., Berber A. Primary prevention of acute respiratory tract infections in children using a bacterial immunostimulant: a double-masked, placebo-controlled clinical trial. Clin Ther. 2000;22(Suppl. 6):748–749.
5. Zaplatnikov A.L. Immunocorrectors of bacterial origin in the prevention and treatment of respiratory infections in children. Russian Pediatric Journal. 2002;1:45–48 (in Russ.)
6. Schaad U.B., Mütterlein R., Goffin H. et al. BV-Child Study Group. Immunostimulation with OM-85 in children with recurrent infections of the upper respiratory tract: a double-blind, placebo-controlled multicenter study. Chest. 2002;122:2042–2049.
7. Markova T.P., Chuvirov D.G. Pathogenetic mechanism of bacterial immune modulators’ action in children with common cold. Current Pediatrics. 2003;1:85–88 (in Russ.).
8. Lanzilli G., Falchetti R., Tricarico M. et al. In vitro effects of an immunostimulating bacterial lysate on human lymphocyte function. Int J Immunopathol Pharmacol. 2005;18:245–254. DOI: 10.1177/039463200501800207.
9. Macchi A., Vecchia L.D. Open comparative, randomized controlled clinical study of a new immunostimulating bacterial lysate in the prophylaxis of upper respiratory tract infections. Arzneimittelforschung. 2005;55:276–281.
10. Del-Rio-Navarro B.E., Espinosa Rosales F., Flenady V., Sienra-Monge J.J. Immunostimulants for preventing respiratory tract infection in children. Cochrane Database Syst Rev. 2006;(4):CD004974. DOI: 10.1002/14651 858. CD004 974.pub2.
11. Karaulov A.V., Kalyuzhin O.V. Immunotropic drugs: principles of application and clinical efficacy. M.: MCFER; 2007 (in Russ.).
12. Schaad U.B. OM-85 BV, an immunostimulant in pediatric recurrent respiratory tract infections: a systematic review. World J Pediatr. 2010;6(1):5–12. DOI: 10.1007/s12519-010-0001-x.
13. Morandi B., Agazzi A., D’Agostino A. et al. A mixture of bacterial mechanical lysates is more efficient than single strain lysate and of bacterial-derived soluble products for the induction of an activating phenotype in human dendritic cells. Immunol Lett. 2011;138(1):86–91. DOI: 10.1016/j.imlet .2011.03.006.
14. Cazzola M., Anapurapu S., Page C.P. Polyvalent mechanical bacterial lysate for the prevention of recurrent respiratory infections: a meta-analysis. Pulm Pharmacol Ther. 2012;25(1):62–68. DOI: 10.1016/j.pupt.2011.11.002.
15. Karpova E.P., Zaplatnikov A.L., Tulupov D.A. Immunoprophylaxis of infections of the upper respiratory tract in the frequently ill children. Vestnik Oto-Rino-Laringologii. 2015;80(5):80–84 (in Russ.) DOI: 10.17116/otorino201580580-84.
16. Kalyuzhin O.V. Topical bacterial lysates in the prevention and treatment of respiratory infections. Practical medicine. 2016;3(95):120–125 (in Russ.).
17. Esposito S., Soto-Martinez M.E., Feleszko W. et al. Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence. Curr Opin Allergy Clin Immunol. 2018;18(3):198–209. DOI: 10.1097/ACI.0000000000000433.
18. Yin J., Xu B., Zeng X., Shen K. Broncho-Vaxom in pediatric recurrent respiratory tract infections: A systematic review and meta-analysis. International Immunopharmacology. 2018;54:98–209. DOI: 10.1016/j.intimp.2017.10.032.
19. Zaplatnikov A.L., Girina A.A., Gluhareva N.S. et al. Polyvalent mechanical bacterial lysate in children with recurrent infections of the respiratory system: using experience, efficacy and safety. Pediatria. 2016;95(6):96–101 (in Russ.).
20. Janeway C.A.Jr. Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harb Symp Quant Biol. 1989;54 Pt 1:1–13. DOI: 10.1101/sqb.1989.054.01.003.
21. Janeway C.A.Jr. The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol Today. 1992;13(1):11–16. DOI: 10.1016/0167-5699(92)90198-G.
22. Medzhitov R., Janeway C.A.J. How does the immune system distinguish self from nonself? Semin Immunol. 2000;12:185–188. DOI: 10.1006/smim.2000.0230.
23. Janeway C.A.Jr., Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197–216. DOI: 10.1146/annurev.immunol.20.083001.084359.
24. Zaplatnikov A.L., Girina A.A., Sugyan N.G. et al. Therapeutic and prophylactic efficacy of polyvalent mechanical bacterial lysate and prospects for its use in pediatric practice. Pediatria. 2019;98(2):113–119 (in Russ.).
25. Khaitov R.M. Immunology. M.: GEOTAR-Media; 2016 (in Russ.).
26. Instructions for medical use of the drug Ismigen®. (Electronic resource.) URL: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=4b4a8cd7-ed2c-4749–8937–93cc4e846bafandt= (access date: 05.28.2021) (in Russ.)
27. Rossi G.A., Peri C., Raynal M.E. et al. Naturally occurring immune response against bacteria commonly involved in upper respiratory tract infections: analysis of the antigen-specific salivary IgA levels. Immunol Lett. 2003;86(1):85–91.
28. Lanzilli G., Falchetti R., Cottarelli A. et al. In vivo effect of an immunostimulating bacterial lysate on human B-lymphocytes. Int J Immunopathol Pharmacol. 2006;19(3):551–559.
29. Braido F., Schenone G., Pallestrini E. et al. The relationship between mucosal immunoresponse and clinical outcome in patients with recurrent upper respiratory tract infections treated with a mechanical bacterial lysate. J Biol Regul Homeost Agents. 2011;25(3):477–485.
30. Lanzilli G., Traggiai E., Braido F. et al. Administration of a polyvalent mechanical bacterial lysate to elderly patients with COPD: Effects on circulating T, B and NK cells. Immunol Lett. 2013;149(1–2):62–67.
31. Rosaschino F., Cattaneo L. Strategies for optimizing compliance of paediatric patients for seasonal antibacterial vaccination with sublingually administered Polyvalent Mechanical Bacterial Lysates. Acta Biomed. 2004;75(3):171–178.
32. Aksic О., Cattaneo L., Rosaschino F. Evaluation of the clinical efficacy of a new polyvalent mechanical bacterial lysate in a population 180 school-age children with recurrent respiratory infections. GEA. 2005;2:1–4.
33. Banche G., Allizond V., Mandras N. et al. Improvement of clinical response in allergic rhinitis patients treated with an oral immunostimulating bacterial lysate: in vivo immunological effects. Int J Immunopathol Pharmacol. 2007;20:129–138.
34. Bartkowiak-Emeryk M. The influence of polyvalent mechanical bacterial lysate on immunological parameters in asthmatic children. European Academy of Allergy and Clinical Immunology Congress. 17–21 June 2017, Helsinki: Abstract 0078.
35. Markova T.P., Kim M.N., Chuvirova A.G.. Ismigen® in complex treatment of children with bronchial asthma. Pediatria. 2017;96(4):159–165 (in Russ.). DOI: 10.24110/0031-403X-2017-96-4-159-165.
36. Bartkowiak-Emeryk M., Emeryk A., Roliński J. et al. Impact of Polyvalent Mechanical Bacterial Lysate on lymphocyte number and activity in asthmatic children: a randomized controlled trial. Allergy Asthma Clin Immunol. 2021;17(1):10. DOI: 10.1186/s13223-020-00503-4.
37. Ferrara F., Rial A., Suárez N., Chabalgoity J.A. Polyvalent Bacterial Lysate Protects Against Pneumonia Independently of Neutrophils, IL-17A or Caspase-1 Activation. Front Immunol. 2021;12:562244. DOI: 10.3389/fimmu.2021.562244.
38. Netea M.G., Quintin J., van der Meer J.W. Trained immunity: a memory for innate host defense. Cell Host Microbe. 2011;9:355–361. DOI: 10.1016/j.chom.2011.04.006.
39. Netea M.G., Dominguez-Andres J., Barreiro L.B. et al. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020;20:375–388. DOI: 10.1038/s41577-020-0285-6.
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