biopreparatБИОпрепараты. Профилактика, диагностика, лечениеBiological Products. Prevention, Diagnosis, Treatment2221-996X2619-1156Scientific Centre for Expert Evaluation of Medicinal Products10.30895/2221-996X-2021-21-1-10-19biopreparat-317Research ArticleОБЗОРЫREVIEWSКоклюшные вакцины и роль липоолигосахарида Bordetella pertussis в иммунном ответе на коклюшную инфекцию и вакцинациюPertussis vaccines and the role of Bordetella pertussis lipooligosaccharide in the immune response to pertussis infection and vaccinationhttps://orcid.org/0000-0001-5586-2933АлексееваИ. А.AlekseevaI. A.

Алексеева Ирина Андреевна, доктор медицинских наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Irina A. Alekseeva, Dr. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

AlekseevaI@expmed.ruhttps://orcid.org/0000-0001-5029-3751ПерелыгинаО. В.PerelyginaO. V.

Перелыгина Ольга Викторовна, кандидат медицинских наук

Петровский б-р, д. 8, стр. 2, Москва, 127051

Olga V. Perelygina, Cand. Sci. (Med.)

8/2 Petrovsky Blvd, Moscow 127051

Pereligina@expmed.ruhttps://orcid.org/0000-0003-4976-483XКолышкинаЕ. Д.KolyshkinaE. D.

Колышкина Елена Дмитриевна

Петровский б-р, д. 8, стр. 2, Москва, 127051

Elena D. Kolyshkina

8/2 Petrovsky Blvd, Moscow 127051

Kolyshkina@expmed.ruФедеральное государственное бюджетное учреждение «Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияScientific Centre for Expert Evaluation of Medicinal ProductsRussian Federation2021290120212111019Copyright © Алексеева И.А., Перелыгина О.В., Колышкина Е.Д., 20212021Алексеева И.А., Перелыгина О.В., Колышкина Е.Д.Alekseeva I.A., Perelygina O.V., Kolyshkina E.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.biopreparations.ru/jour/article/view/317

В научной литературе опубликованы данные, свидетельствующие о «возвращении», «возрождении» коклюша. Проблема предупреждения и ликвидации заболеваемости коклюшем может быть решена только с помощью активной иммунизации восприимчивых контингентов высокоэффективной вакциной. Цель работы — охарактеризовать используемые в настоящее время цельноклеточные и бесклеточные коклюшные вакцины и оценить перспективу повышения их качества, в частности показать роль липоолигосахарида — антигена клеточной стенки Bordetella pertussis — в индуцировании адаптивного иммунитета. В статье кратко изложена схема патогенеза коклюшной инфекции, особенности формирования постинфекционного и поствакцинального противококлюшного иммунитета и рассмотрены способы улучшения коклюшных вакцин. Повышение качества существующих вакцин связано со снижением реактогенности цельноклеточной коклюшной вакцины и повышением иммуногенной активности бесклеточной коклюшной вакцины. Одна из возможностей понижения реактогенности цельноклеточной вакцины заключается в уменьшении количества коклюшных клеток в дозе вакцины при условии, что эти действия не отразятся на иммуногенной активности препарата. Другой возможный путь снижения реактогенности может заключаться в отборе вакцинных штаммов по содержанию в них эндотоксина липоолигосахарида (ЛОС). Для улучшения качества бесклеточных вакцин необходимо решить многие проблемы. Одна из них заключается в поиске и выделении новых протективных антигенов. В результате анализа данных литературы продемонстрировано, что ЛОС является чрезвычайно важным антигеном, участвующим в иммунном ответе организма и обеспечивающим Тh1- и Th17-клеточный ответ на коклюшную инфекцию, что является определяющим при борьбе с бактериями B. pertussis. Учитывая эволюционную стабильность структуры ЛОС, этот антиген (его нетоксичная олигосахаридная часть) может рассматриваться в качестве кандидата в состав бесклеточной коклюшной вакцины.

Some scientific publications contain data suggesting the “return” or “resurgence” of pertussis. Prevention and elimination of pertussis can only be achieved by extensive immunisation of susceptible populations with a highly effective vaccine. The aim of the study was to characterise available whole-cell and acellular pertussis vaccines and to assess the feasibility of improving their quality, for instance, to demonstrate the role of lipooligosaccharide (LOS)—Bordetella pertussis cell wall antigen—in the induction of adaptive immunity. The paper summarises pathogenesis of pertussis, development of post-infection and post-vaccination immunity, and potential ways of improving pertussis vaccines. Improvement of quality of available vaccines can be achieved by reducing reactogenicity of whole-cell pertussis vaccines and enhancing immunogenic activity of acellular pertussis vaccines. One way to reduce reactogenicity of a whole-cell vaccine is to reduce the number of pertussis cells in the vaccine dose, provided that this does not affect the immunogenic activity of the product. Another possible way of reducing reactogenicity is to select vaccine strains based on the LOS endotoxin content. Improvement of acellular vaccine quality involves addressing many issues, such as identification and isolation of new protective antigens. Literature review demonstrated that LOS is a key antigen, because it is involved in the body’s immune response and ensures Th1 and Th17 cell responses to pertussis, which is crucial for protection from B. pertussis bacteria. Considering the evolutionary stability of the LOS structure, this antigen (i.e. its non-toxic oligosaccharide part) can be considered as a candidate for acellular pertussis vaccine.

коклюшцельноклеточная коклюшная вакцинабесклеточная коклюшная вакциналипоолигосахарид Bordetella pertussispertussiswhole-cell pertussis vaccineacellular pertussis vaccineBordetella pertussis lipooligosaccharideРабота выполнена в рамках государственного задания ФГБУ «НЦЭСМП» Минздрава России № 056-00005-21-00 на проведение прикладных научных исследований (номер государственного учета НИР 121022000147-4).The study reported in this publication was carried out as part of a publicly funded research project No. 056-00005-21-00 and was supported by the Scientific Centre for Expert Evaluation of Medicinal Products (R&D public accounting No. 121022000147-4).ReferencesMattoo S, Cherry JD. Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies. Clin Microbiol Rev. 2005;18(2):326–82. https://doi.org/10.1128/CMR.18.2.326-382.2005Mattoo S, Cherry JD. Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies. Clin Microbiol Rev. 2005;18(2):326–82. https://doi.org/10.1128/CMR.18.2.326-382.2005Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet. 2010;375(9730):1969–87. https://doi.org/10.1016/S0140-6736(10)60549-1Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, et al. Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet. 2010;375(9730):1969–87. https://doi.org/10.1016/S0140-6736(10)60549-1Paddock CD, Sanden GN, Cherry JD, Gal AA, Langston C, Tatti KM, et al. Pathology and pathogenesis of fatal Bordetella pertussis infection in infants. Clin Infect Dis. 2008;47(3):328– 38. https://doi.org/10.1086/589753Paddock CD, Sanden GN, Cherry JD, Gal AA, Langston C, Tatti KM, et al. Pathology and pathogenesis of fatal Bordetella pertussis infection in infants. Clin Infect Dis. 2008;47(3):328– 38. https://doi.org/10.1086/589753Melvin JA, Scheller EV, Miller JF, Cotter PA. Bordetella pertussis pathogenesis: current and future challenges. Nat Rev Microbiol. 2014;12(4):274–88. https://doi.org/10.1038/nrmicro3235Melvin JA, Scheller EV, Miller JF, Cotter PA. Bordetella pertussis pathogenesis: current and future challenges. Nat Rev Microbiol. 2014;12(4):274–88. https://doi.org/10.1038/nrmicro3235Marzouqi I, Richmond P, Fry S, Wetherall J, Mukkur T. Development of improved vaccines against whooping cough: current status. Hum Vaccin. 2010;6(7):543–53. https://doi.org/10.4161/hv.6.7.11413Marzouqi I, Richmond P, Fry S, Wetherall J, Mukkur T. Development of improved vaccines against whooping cough: current status. Hum Vaccin. 2010;6(7):543–53. https://doi.org/10.4161/hv.6.7.11413Miller D, Madge N, Diamond J, Wadsworth J, Ross E. Pertussis immunisation and serious acute neurological illnesses in children. BMJ. 1993;307(6913):1171–6. https://doi.org/10.1136/bmj.307.6913.1171Miller D, Madge N, Diamond J, Wadsworth J, Ross E. Pertussis immunisation and serious acute neurological illnesses in children. BMJ. 1993;307(6913):1171–6. https://doi.org/10.1136/bmj.307.6913.1171Guiso N. Bordetella pertussis and pertussis vaccines. Clin Infect Dis. 2009;49(10):1565–9. https://doi.org/10.1086/644733Guiso N. Bordetella pertussis and pertussis vaccines. Clin Infect Dis. 2009;49(10):1565–9. https://doi.org/10.1086/644733Cherry JD. Epidemic pertussis in 2012 — the resurgence of a vaccine-preventable disease. N Engl J Med. 2012;367(9):785–7. https://doi.org/10.1056/NEJMp1209051Cherry JD. Epidemic pertussis in 2012 — the resurgence of a vaccine-preventable disease. N Engl J Med. 2012;367(9):785–7. https://doi.org/10.1056/NEJMp1209051Witt MA, Arias L, Katz PH, Truong ET, Witt DJ. Reduced risk of pertussis among persons ever vaccinated with whole cell pertussis vaccine compared to recipients of acellular pertussis vaccines in a large US cohort. Clin Infect Dis. 2013;56(9):1248–54. https://doi.org/10.1093/cid/cit046Witt MA, Arias L, Katz PH, Truong ET, Witt DJ. Reduced risk of pertussis among persons ever vaccinated with whole cell pertussis vaccine compared to recipients of acellular pertussis vaccines in a large US cohort. Clin Infect Dis. 2013;56(9):1248–54. https://doi.org/10.1093/cid/cit046King AJ, van der Lee S, Mohangoo A, van Gent M, van der Ark A, van de Waterbeemd B. Genome-wide gene expression analysis of Bordetella pertussis isolates associated with a resurgence in pertussis: elucidation of factors involved in the increased fitness of epidemic strains. PLoS One. 2013;8(6):e66150. https://doi.org/10.1371/journal.pone.0066150King AJ, van der Lee S, Mohangoo A, van Gent M, van der Ark A, van de Waterbeemd B. Genome-wide gene expression analysis of Bordetella pertussis isolates associated with a resurgence in pertussis: elucidation of factors involved in the increased fitness of epidemic strains. PLoS One. 2013;8(6):e66150. https://doi.org/10.1371/journal.pone.0066150Amirthalingam G, Gupta S, Campbell H. Pertussis immunisation and control in England and Wales, 1957 to 2012: a historical review. Euro Surveill. 2013;18(38):20587. https://doi.org/10.2807/1560-7917.es2013.18.38.20587Amirthalingam G, Gupta S, Campbell H. Pertussis immunisation and control in England and Wales, 1957 to 2012: a historical review. Euro Surveill. 2013;18(38):20587. https://doi.org/10.2807/1560-7917.es2013.18.38.20587Halperin BA, Halperin SA. The reemergence of pertussis and infant deaths: is it time to immunize pregnant women? Future Microbiol. 2011;6(4):367–9. https://doi.org/10.2217/fmb.11.15Halperin BA, Halperin SA. The reemergence of pertussis and infant deaths: is it time to immunize pregnant women? Future Microbiol. 2011;6(4):367–9. https://doi.org/10.2217/fmb.11.15Poland GA. Pertussis outbreaks and pertussis vaccines: new insights, new concerns, new recommendations? Vaccine. 2012;30(49):6957–9. https://doi.org/10.1016/j.vaccine.2012.09.084Poland GA. Pertussis outbreaks and pertussis vaccines: new insights, new concerns, new recommendations? Vaccine. 2012;30(49):6957–9. https://doi.org/10.1016/j.vaccine.2012.09.084Klein NP, Bartlett J, Fireman B, Baxter R. Waning Tdap effectiveness in adolescents. Pediatrics. 2016;137(3):e20153326. https://doi.org/10.1542/peds.2015-3326Klein NP, Bartlett J, Fireman B, Baxter R. Waning Tdap effectiveness in adolescents. Pediatrics. 2016;137(3):e20153326. https://doi.org/10.1542/peds.2015-3326Gu XX, Plotkin SA, Edwards KM, Sette A, Mills KHG, Levy O, et al. Waning immunity and microbial vaccines — Workshop of the National Institute of Allergy and Infectious Diseases. Clin Vaccine Immunol. 2017;24(7):e00034–17. https://doi.org/10.1128/cvi.00034-17Gu XX, Plotkin SA, Edwards KM, Sette A, Mills KHG, Levy O, et al. Waning immunity and microbial vaccines — Workshop of the National Institute of Allergy and Infectious Diseases. Clin Vaccine Immunol. 2017;24(7):e00034–17. https://doi.org/10.1128/cvi.00034-17Mooi FR, Van Der Maas NA, De Melker HE. Pertussis resurgence: waning immunity and pathogen adaptation — two sides of the same coin. Epidemiol Infect. 2014;142(4):685– 94. https://doi.org/10.1017/S0950268813000071Mooi FR, Van Der Maas NA, De Melker HE. Pertussis resurgence: waning immunity and pathogen adaptation — two sides of the same coin. Epidemiol Infect. 2014;142(4):685– 94. https://doi.org/10.1017/S0950268813000071Schmidtke AJ, Boney KO, Martin SW, Skoff TH, Tondella ML, Tatti KM. Population diversity among Bordetella pertussis isolates, United States, 1935–2009. Emerg Infect Dis. 2012;18(8):1248–55. https://doi.org/10.3201/eid1808.120082Schmidtke AJ, Boney KO, Martin SW, Skoff TH, Tondella ML, Tatti KM. Population diversity among Bordetella pertussis isolates, United States, 1935–2009. Emerg Infect Dis. 2012;18(8):1248–55. https://doi.org/10.3201/eid1808.120082Sheridan SL, McCall BJ, Davis CA, Robson JMB, Hull BP, Selvey CE, et al. Acellular pertussis vaccine effectiveness for children during the 2009–2010 pertussis epidemic in Queensland. Med J Aust. 2014;200(6):334–8. https://doi.org/10.5694/mja13.11069Sheridan SL, McCall BJ, Davis CA, Robson JMB, Hull BP, Selvey CE, et al. Acellular pertussis vaccine effectiveness for children during the 2009–2010 pertussis epidemic in Queensland. Med J Aust. 2014;200(6):334–8. https://doi.org/10.5694/mja13.11069Tartof SY, Lewis M, Kenyon C, White K, Osborn A, Liko J, et al. Waning immunity to pertussis following 5 doses of DTaP. Pediatrics. 2013;131(4):e1047–52. https://doi.org/10.1542/peds.2012-1928Tartof SY, Lewis M, Kenyon C, White K, Osborn A, Liko J, et al. Waning immunity to pertussis following 5 doses of DTaP. Pediatrics. 2013;131(4):e1047–52. https://doi.org/10.1542/peds.2012-1928de Gouw D, Hermans PWM, Bootsma HJ, Zomer A, Heuvelman K, Diavatopoulos DA, Mooi FR. Differentially expressed genes in Bordetella pertussis strains belonging to a lineage which recently spread globally. PLoS ONE. 2014;9(1):e84523. https://doi.org/10.1371/journal.pone.0084523de Gouw D, Hermans PWM, Bootsma HJ, Zomer A, Heuvelman K, Diavatopoulos DA, Mooi FR. Differentially expressed genes in Bordetella pertussis strains belonging to a lineage which recently spread globally. PLoS ONE. 2014;9(1):e84523. https://doi.org/10.1371/journal.pone.0084523Breakwell L, Kelso P, Finley C, Schoenfeld S, Goode B, Misegades LK, et al. Pertussis vaccine effectiveness in the setting of pertactin-deficient pertussis. Pediatrics. 2016;137(5):e20153973. https://doi.org/10.1542/peds.2015- 3973Breakwell L, Kelso P, Finley C, Schoenfeld S, Goode B, Misegades LK, et al. Pertussis vaccine effectiveness in the setting of pertactin-deficient pertussis. Pediatrics. 2016;137(5):e20153973. https://doi.org/10.1542/peds.2015- 3973Lam C, Octavia S, Ricafort L, Sintchenko V, Gilbert GL, Wood N, et al. Rapid increase in pertactin-deficient Bordetella pertussis isolates, Australia. Emerg Infect Dis. 2014;20(4):626–33. https://doi.org/10.3201/eid2004.131478Lam C, Octavia S, Ricafort L, Sintchenko V, Gilbert GL, Wood N, et al. Rapid increase in pertactin-deficient Bordetella pertussis isolates, Australia. Emerg Infect Dis. 2014;20(4):626–33. https://doi.org/10.3201/eid2004.131478Zeddeman A, van Gent M, Heuvelman CJ, van der Heide HG, Bart MJ, Advaniet A, et al. Investigations into the emergence of pertactin-deficient Bordetella pertussis isolates in six European countries, 1996 to 2012. Euro Surveill. 2014;19(33):20881. https://doi.org/10.2807/1560-7917.es2014.19.33.20881Zeddeman A, van Gent M, Heuvelman CJ, van der Heide HG, Bart MJ, Advaniet A, et al. Investigations into the emergence of pertactin-deficient Bordetella pertussis isolates in six European countries, 1996 to 2012. Euro Surveill. 2014;19(33):20881. https://doi.org/10.2807/1560-7917.es2014.19.33.20881Otsuka N, Han HJ, Toyoizumi-Ajisaka H, Nakamura Y, Arakawa Y, Shibayama K, Kamachi K. Prevalence and genetic characterization of pertactin-deficient Bordetella pertussis in Japan. PLoS ONE. 2012;7(2):e31985. https://doi.org/10.1371/journal.pone.0031985Otsuka N, Han HJ, Toyoizumi-Ajisaka H, Nakamura Y, Arakawa Y, Shibayama K, Kamachi K. Prevalence and genetic characterization of pertactin-deficient Bordetella pertussis in Japan. PLoS ONE. 2012;7(2):e31985. https://doi.org/10.1371/journal.pone.0031985Martin SW, Pawloski L, Williams M, Weening K, DeBolt C, Qin X, et al. Pertactin-negative Bordetella pertussis strains: evidence for a possible selective advantage. Clin Infect Dis. 2015;60(2):223–7. https://doi.org/10.1093/cid/ciu788Martin SW, Pawloski L, Williams M, Weening K, DeBolt C, Qin X, et al. Pertactin-negative Bordetella pertussis strains: evidence for a possible selective advantage. Clin Infect Dis. 2015;60(2):223–7. https://doi.org/10.1093/cid/ciu788Bouchez V, Brun D, Cantinelli T, Dore G, Njamkepo E, Guiso N. First report and detailed characterization of B. pertussis isolates not expressing pertussis toxin or pertactin. Vaccine. 2009;27(43):6034–41. https://doi.org/10.1016/j.vaccine.2009.07.074Bouchez V, Brun D, Cantinelli T, Dore G, Njamkepo E, Guiso N. First report and detailed characterization of B. pertussis isolates not expressing pertussis toxin or pertactin. Vaccine. 2009;27(43):6034–41. https://doi.org/10.1016/j.vaccine.2009.07.074Bodilis H, Guiso N. Virulence of pertactin-negative Bordetella pertussis isolates from infants, France. Emerg Infect Dis. 2013;19(3):471–4. https://doi.org/10.3201/1903.121475Bodilis H, Guiso N. Virulence of pertactin-negative Bordetella pertussis isolates from infants, France. Emerg Infect Dis. 2013;19(3):471–4. https://doi.org/10.3201/1903.121475Williams MM, Sen K, Weigand MR, Skoff TH, Cunningham VA, Halse TA, et al. Bordetella pertussis strain lacking pertactin and pertussis toxin. Emerg Infect Dis. 2016;22(2):319–22. https://doi.org/10.3201/eid2202.151332Williams MM, Sen K, Weigand MR, Skoff TH, Cunningham VA, Halse TA, et al. Bordetella pertussis strain lacking pertactin and pertussis toxin. Emerg Infect Dis. 2016;22(2):319–22. https://doi.org/10.3201/eid2202.151332Hozbor D. New pertussis vaccines: a need and a challenge. In: Fedele G, Ausiello C, eds. Pertussis Infection and Vaccines. Advances in Experimental Medicine and Biology. Vol 1183. Springer, Cham; 2019. P. 115–26. https://doi.org/10.1007/5584_2019_407Hozbor D. New pertussis vaccines: a need and a challenge. In: Fedele G, Ausiello C, eds. Pertussis Infection and Vaccines. Advances in Experimental Medicine and Biology. Vol 1183. Springer, Cham; 2019. P. 115–26. https://doi.org/10.1007/5584_2019_407Locht C, Papin JF, Lecher S, Debrie AS, Thalen M, Solovay K, et al. Live attenuated pertussis vaccine BPZE1 protects baboons against Bordetella pertussis disease and infection. J Infect Dis. 2017;216(1):117–24. https://doi.org/10.1093/infdis/ jix254Locht C, Papin JF, Lecher S, Debrie AS, Thalen M, Solovay K, et al. Live attenuated pertussis vaccine BPZE1 protects baboons against Bordetella pertussis disease and infection. J Infect Dis. 2017;216(1):117–24. https://doi.org/10.1093/infdis/ jix254Li P, Asokanathan C, Liu F, Khaing KK, Kmiec D, Wei X, et al. PLGA nano/micro particles encapsulated with pertussis toxoid (PTd) enhances Th1/Th17 immune response in a murine model. Int J Pharm. 2016;513(1–2):183–90. https://doi.org/10.1016/j.ijpharm.2016.08.059Li P, Asokanathan C, Liu F, Khaing KK, Kmiec D, Wei X, et al. PLGA nano/micro particles encapsulated with pertussis toxoid (PTd) enhances Th1/Th17 immune response in a murine model. Int J Pharm. 2016;513(1–2):183–90. https://doi.org/10.1016/j.ijpharm.2016.08.059Koj S, Ługowski C, Niedziela T. Neoglikokoniugaty lipooligosacharydu Bordetella pertussis-nowe potencjalne składniki szczepionki przeciwkrztuścowej. Postepy Hig Med Dosw (Online). 2015;69:1013–30.Koj S, Ługowski C, Niedziela T. Bordetella pertussis lipooligosaccharide-derived neoglycoconjugates — new components of pertussis vaccine. Postepy Hig Med Dosw (Online). 2015;69:1013– 30 (In Polish)Farizo KM, Burns DL, Finn TM, Gruber MF, Pratt RD. Clinical evaluation of pertussis vaccines: US Food and Drug Administration regulatory considerations. J Infect Dis. 2014;209(Suppl 1):S28–31. https://doi.org/10.1093/infdis/jit532Farizo KM, Burns DL, Finn TM, Gruber MF, Pratt RD. Clinical evaluation of pertussis vaccines: US Food and Drug Administration regulatory considerations. J Infect Dis. 2014;209(Suppl 1):S28–31. https://doi.org/10.1093/infdis/jit532Cervantes GE. Bordetella pertussis: reemergente. Rev Mex Patol Clin Med Lab. 2018;65(1):18–21.Cervantes GE. Bordetella pertussis: reemergente. Rev Mex Patol Clin Med Lab. 2018;65(1):18–21.Flak TA, Goldman WE. Signalling and cellular specificity of airway nitric oxide production in pertussis. Cell Microbiol. 1999;1(1):51–60. https://doi.org/10.1046/j.1462-5822.1999.00004.xFlak TA, Goldman WE. Signalling and cellular specificity of airway nitric oxide production in pertussis. Cell Microbiol. 1999;1(1):51–60. https://doi.org/10.1046/j.1462-5822.1999.00004.xWeiss AA, Mobberley PS, Fernandez RC, Mink CM. Characterization of human bactericidal antibodies to Bordetella pertussis. Infect Immun. 1999;67(3):1424–31. https://doi.org/10.1128/IAI.67.3.1424-1431.1999Weiss AA, Mobberley PS, Fernandez RC, Mink CM. Characterization of human bactericidal antibodies to Bordetella pertussis. Infect Immun. 1999;67(3):1424–31. https://doi.org/10.1128/IAI.67.3.1424-1431.1999Trollfors B, Lagergård T, Taranger J, Bergfors E, Schneerson R, Robbins JB. Serum immunoglobulin G antibody responses to Bordetella pertussis lipooligosaccharide and B. parapertussis lipopolysaccharide in children with pertussis and parapertussis. Clin Diagn Lab Immunol. 2001;8(5):1015– 7. https://doi.org/10.1128/CDLI.8.5.1015-1017.2001Trollfors B, Lagergård T, Taranger J, Bergfors E, Schneerson R, Robbins JB. Serum immunoglobulin G antibody responses to Bordetella pertussis lipooligosaccharide and B. parapertussis lipopolysaccharide in children with pertussis and parapertussis. Clin Diagn Lab Immunol. 2001;8(5):1015– 7. https://doi.org/10.1128/CDLI.8.5.1015-1017.2001Elder KD, Harvill ET. Strain-dependent role of BrkA during Bordetella pertussis infection of the murine respiratory tract. Infect Immun. 2004;72(10):5919–24. https://doi.org/10.1128/IAI.72.10.5919-5924.2004Elder KD, Harvill ET. Strain-dependent role of BrkA during Bordetella pertussis infection of the murine respiratory tract. Infect Immun. 2004;72(10):5919–24. https://doi.org/10.1128/IAI.72.10.5919-5924.2004Elomaa A, Qiushui He, Nhu Nguyen Tran Minh, Mertsola J. Pertussis before and after the introduction of acellular pertussis vaccines in Finland. Vaccine. 2009;27(40):5443–9. https://doi.org/10.1016/j.vaccine.2009.07.010Elomaa A, Qiushui He, Nhu Nguyen Tran Minh, Mertsola J. Pertussis before and after the introduction of acellular pertussis vaccines in Finland. Vaccine. 2009;27(40):5443–9. https://doi.org/10.1016/j.vaccine.2009.07.010Steinman RM, Hemmi H. Dendritic Cells: Translating innate to adaptive immunity. In: Pulendran B, Ahmed R, eds. From Innate Immunity to Immunological Memory. Current Topics in Microbiology and Immunology. Vol 311. Springer, Berlin, Heidelberg; 2006. P. 17–58. https://doi.org/10.1007/3-540-32636-7_2Steinman RM, Hemmi H. Dendritic Cells: Translating innate to adaptive immunity. In: Pulendran B, Ahmed R, eds. From Innate Immunity to Immunological Memory. Current Topics in Microbiology and Immunology. Vol 311. Springer, Berlin, Heidelberg; 2006. P. 17–58. https://doi.org/10.1007/3-540-32636-7_2Beutler B, Hoebe K, Du X, Ulevitch RJ. How we detect microbes and respond to them: the Toll-like receptors and their transducers. J Leukoc Biol. 2003;74(4):479–85. https://doi.org/10.1189/jlb.0203082Beutler B, Hoebe K, Du X, Ulevitch RJ. How we detect microbes and respond to them: the Toll-like receptors and their transducers. J Leukoc Biol. 2003;74(4):479–85. https://doi.org/10.1189/jlb.0203082Triantafilou M, Brandenburg K, Kusumoto S, Fukase K, Mackie A, Seyde U, Triantafilou K. Combinational clustering of receptors following stimulation by bacterial products determines lipopolysaccharide responses. Biochem J. 2004;381(2):527–36. https://doi.org/10.1042/BJ20040172Triantafilou M, Brandenburg K, Kusumoto S, Fukase K, Mackie A, Seyde U, Triantafilou K. Combinational clustering of receptors following stimulation by bacterial products determines lipopolysaccharide responses. Biochem J. 2004;381(2):527–36. https://doi.org/10.1042/BJ20040172Mills KH, Ross PJ, Allen AC, Wilk MM. Do we need a new vaccine to control the re-emergence of pertussis? Trends Microbiol. 2014;22(2):49–52. https://doi.org/10.1016/j.tim.2013.11.007Mills KH, Ross PJ, Allen AC, Wilk MM. Do we need a new vaccine to control the re-emergence of pertussis? Trends Microbiol. 2014;22(2):49–52. https://doi.org/10.1016/j.tim.2013.11.007Siciliano NA, Skinner JA, Yuk MH. Bordetella bronchiseptica modulates macrophage phenotype leading to the inhibition of CD4+ T cell proliferation and the initiation of a Th17 immune response. J Immunol. 2006;177(10):7131–8. https://doi.org/10.4049/jimmunol.177.10.7131Siciliano NA, Skinner JA, Yuk MH. Bordetella bronchiseptica modulates macrophage phenotype leading to the inhibition of CD4+ T cell proliferation and the initiation of a Th17 immune response. J Immunol. 2006;177(10):7131–8. https://doi.org/10.4049/jimmunol.177.10.7131Dabbagh K, Lewis DB. Toll-like receptors and Thelper-1/T-helper-2 responses. Curr Opin Infect Dis. 2003;16(3):199–204. https://doi.org/10.1097/00001432-200306000-00003Dabbagh K, Lewis DB. Toll-like receptors and Thelper-1/T-helper-2 responses. Curr Opin Infect Dis. 2003;16(3):199–204. https://doi.org/10.1097/00001432-200306000-00003Kapsenberg ML. Dendritic-cell control of pathogen-driven T-cell polarization. Nat Rev Immunol. 2003;3(12):984–93. https://doi.org/10.1038/nri1246Kapsenberg ML. Dendritic-cell control of pathogen-driven T-cell polarization. Nat Rev Immunol. 2003;3(12):984–93. https://doi.org/10.1038/nri1246Warfel JM, Merkel TJ. The baboon model of pertussis: effective use and lessons for pertussis vaccines. Expert Rev Vaccines. 2014;13(10):1241–52. https://doi.org/10.1586/14760584.2014.946016Warfel JM, Merkel TJ. The baboon model of pertussis: effective use and lessons for pertussis vaccines. Expert Rev Vaccines. 2014;13(10):1241–52. https://doi.org/10.1586/14760584.2014.946016Higgins SC, Jarnicki AG, Lavelle EC, Mills KH. TLR4 mediates vaccine-induced protective cellular immunity to Bordetella pertussis: role of IL-17-producing T cells. J Immunol. 2006;177(11):7980–9. https://doi.org/10.4049/jimmunol.177.11.7980Higgins SC, Jarnicki AG, Lavelle EC, Mills KH. TLR4 mediates vaccine-induced protective cellular immunity to Bordetella pertussis: role of IL-17-producing T cells. J Immunol. 2006;177(11):7980–9. https://doi.org/10.4049/jimmunol.177.11.7980van den Berg BM, David S, Beekhuizen H, Mooi FR, van Furth R. Protection and humoral immune responses against Bordetella pertussis infection in mice immunized with acellular or cellular pertussis immunogens. Vaccine. 2000;19(9–10):1118–28. https://doi.org/10.1016/s0264-410x(00)00329-7van den Berg BM, David S, Beekhuizen H, Mooi FR, van Furth R. Protection and humoral immune responses against Bordetella pertussis infection in mice immunized with acellular or cellular pertussis immunogens. Vaccine. 2000;19(9–10):1118–28. https://doi.org/10.1016/s0264-410x(00)00329-7Gzyl A, Augustynowicz E, Zawadka M, Rabczenko D, Slusarczyk J. Ocena efektywności pełnokomórkowych i bezkomórkowych szczepionek przeciw krztuścowi w eliminacji eksperymentalnego zakazenia myszy Bordetella pertussis. Med Dosw Mikrobiol. 2007;59(2):123–35.Gzyl A, Augustynowicz E, Zawadka M, Rabczenko D, Slusarczyk J. Evaluation of whole-cell and acellular pertussis vaccines effectiveness in clearance of experimental B. pertussis infection in mice. Med Dosw Mikrobiol. 2007;59(2):123–35 (In Polish)Brummelman J, Helm K, Hamstra HJ, van der Ley P, Boog CJ, Han WG, et al. Modulation of the CD4+ T cell response after acellular pertussis vaccination in the presence of TLR4 ligation. Vaccine. 2015;33(12):1483–91. https://doi.org/10.1016/j.vaccine.2015.01.063Brummelman J, Helm K, Hamstra HJ, van der Ley P, Boog CJ, Han WG, et al. Modulation of the CD4+ T cell response after acellular pertussis vaccination in the presence of TLR4 ligation. Vaccine. 2015;33(12):1483–91. https://doi.org/10.1016/j.vaccine.2015.01.063Mahon BP, Sheahan BJ, Griffin F, Murphy G, Mills KH. Atypical disease after Bordetella pertussis respiratory infection of mice with targeted disruptions of interferongamma receptor or immunoglobulin μ chain genes. J Exp Med. 1997;186(11):1843–51. https://doi.org/10.1084/jem.186.11.1843Mahon BP, Sheahan BJ, Griffin F, Murphy G, Mills KH. Atypical disease after Bordetella pertussis respiratory infection of mice with targeted disruptions of interferongamma receptor or immunoglobulin μ chain genes. J Exp Med. 1997;186(11):1843–51. https://doi.org/10.1084/jem.186.11.1843Weiss AA, Patton AK, Millen SH, Chang SJ, Ward JI, Bernstein DI. Acellular pertussis vaccines and complement killing of Bordetella pertussis. Infect Immun. 2004;72(12):7346–51. https://doi.org/10.1128/IAI.72.12.7346-7351.2004Weiss AA, Patton AK, Millen SH, Chang SJ, Ward JI, Bernstein DI. Acellular pertussis vaccines and complement killing of Bordetella pertussis. Infect Immun. 2004;72(12):7346–51. https://doi.org/10.1128/IAI.72.12.7346-7351.2004Albitar-Nehme S, Basheer SM, Njamkepo E, Brisson JR, Guiso N, Caroff M. Comparison of lipopolysaccharide structures of Bordetella pertussis clinical isolates from pre- and post-vaccine era. Carbohydr Res. 2013;378:56–62. https://doi.org/10.1016/j.carres.2013.05.002Albitar-Nehme S, Basheer SM, Njamkepo E, Brisson JR, Guiso N, Caroff M. Comparison of lipopolysaccharide structures of Bordetella pertussis clinical isolates from pre- and post-vaccine era. Carbohydr Res. 2013;378:56–62. https://doi.org/10.1016/j.carres.2013.05.002Schaeffer LM, McCormack FX, Wu H, Weiss AA. Bordetella pertussis lipopolysaccharide resists the bactericidal effects of pulmonary surfactant protein A. J Immunol. 2004;173(3):1959–65. https://doi.org/10.4049/jimmunol.173.3.1959Schaeffer LM, McCormack FX, Wu H, Weiss AA. Bordetella pertussis lipopolysaccharide resists the bactericidal effects of pulmonary surfactant protein A. J Immunol. 2004;173(3):1959–65. https://doi.org/10.4049/jimmunol.173.3.1959Geurtsen J, Vandebriel RJ, Gremmer ER, Kuipers B, Tommassen J, van der Ley P. Consequences of the expression of lipopolysaccharide-modifying enzymes for the efficacy and reactogenicity of whole-cell pertussis vaccines. Microbes Infect. 2007;9(9):1096–103. https://doi.org/10.1016/j.micinf.2007.04.015Geurtsen J, Vandebriel RJ, Gremmer ER, Kuipers B, Tommassen J, van der Ley P. Consequences of the expression of lipopolysaccharide-modifying enzymes for the efficacy and reactogenicity of whole-cell pertussis vaccines. Microbes Infect. 2007;9(9):1096–103. https://doi.org/10.1016/j.micinf.2007.04.015Caroff M, Karibian D. Structure of bacterial lipopolysaccharides. Carbohydr Res. 2003;338(23):2431–47. https://doi.org/10.1016/j.carres.2003.07.010Caroff M, Karibian D. Structure of bacterial lipopolysaccharides. Carbohydr Res. 2003;338(23):2431–47. https://doi.org/10.1016/j.carres.2003.07.010Whitfield C, Trent MS. Biosynthesis and export of bacterial lipopolysaccharides. Annu Rev Biochem. 2014;83:99–128. https://doi.org/10.1146/annurev-biochem-060713-035600Whitfield C, Trent MS. Biosynthesis and export of bacterial lipopolysaccharides. Annu Rev Biochem. 2014;83:99–128. https://doi.org/10.1146/annurev-biochem-060713-035600Nikaido H, Vaara M. Outer membrane. In: Neidhardt FC, Ingraham JL, Low KB, Magasanik B, Schaechter M, Umbarger HE, eds. Escherichia coli and Salmonella typhimurium — cellular and molecular biology. Washington DC: ASM; 1987. P. 7–22.Nikaido H, Vaara M. Outer membrane. In: Neidhardt FC, Ingraham JL, Low KB, Magasanik B, Schaechter M, Umbarger HE, eds. Escherichia coli and Salmonella typhimurium — cellular and molecular biology. Washington DC: ASM; 1987. P. 7–22.Sperandeo P, Martorana AM, Polissi A. Lipopolysaccharide biogenesis and transport at the outer membrane of Gramnegative bacteria. Biochim Biophys Acta Mol Cell Biol Lipids. 2017;1862(11):1451–60. https://doi.org/10.1016/j.bbalip.2016.10.006Sperandeo P, Martorana AM, Polissi A. Lipopolysaccharide biogenesis and transport at the outer membrane of Gramnegative bacteria. Biochim Biophys Acta Mol Cell Biol Lipids. 2017;1862(11):1451–60. https://doi.org/10.1016/j.bbalip.2016.10.006Nikaido H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev. 2003;67(4):593– 656. https://doi.org/10.1128/mmbr.67.4.593-656.2003Nikaido H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev. 2003;67(4):593– 656. https://doi.org/10.1128/mmbr.67.4.593-656.2003Park BS, Lee JO. Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp Mol Med. 2013;45(12):e66. https://doi.org/10.1038/emm.2013.97Park BS, Lee JO. Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp Mol Med. 2013;45(12):e66. https://doi.org/10.1038/emm.2013.97Caroff M, Deprun C, Richards JC, Karibian D. Structural characterization of the lipid A of Bordetella pertussis 1414 endotoxin. J Bacteriol. 1994;176(16):5156–9. https://doi.org/10.1128/jb.176.16.5156-5159.1994Caroff M, Deprun C, Richards JC, Karibian D. Structural characterization of the lipid A of Bordetella pertussis 1414 endotoxin. J Bacteriol. 1994;176(16):5156–9. https://doi.org/10.1128/jb.176.16.5156-5159.1994Gaudet RG, Sintsova A, Buckwalter CM, Leung N, Cochrane A, Li J, et al. Cytosolic detection of the bacterial metabolite HBP activates TIFA-dependent innate immunity. Science. 2015;348(6240):1251–5. https://doi.org/10.1126/science.aaa4921Gaudet RG, Sintsova A, Buckwalter CM, Leung N, Cochrane A, Li J, et al. Cytosolic detection of the bacterial metabolite HBP activates TIFA-dependent innate immunity. Science. 2015;348(6240):1251–5. https://doi.org/10.1126/science.aaa4921Preston A, Mandrell RE, Gibson BW, Apicella MA. The lipooligosaccharides of pathogenic Gram-negative bacteria. Crit Rev Microbiol. 1996;22(3):139–80. https://doi.org/10.3109/10408419609106458Preston A, Mandrell RE, Gibson BW, Apicella MA. The lipooligosaccharides of pathogenic Gram-negative bacteria. Crit Rev Microbiol. 1996;22(3):139–80. https://doi.org/10.3109/10408419609106458Munford RS. Sensing Gram-negative bacterial lipopolysaccharides: a human disease determinant? Infect Immun. 2008;76(2):454–65. https://doi.org/10.1128/IAI.00939-07Munford RS. Sensing Gram-negative bacterial lipopolysaccharides: a human disease determinant? Infect Immun. 2008;76(2):454–65. https://doi.org/10.1128/IAI.00939-07Gotto JW, Eckhardt T, Reilly PA, Scott JV, Cowell JL, Metcalf TN, 3rd, et al. Biochemical and immunological properties of two forms of pertactin, the 69,000-molecular-weight outer membrane protein of Bordetella pertussis. Infect Immun. 1993;61(5):2211–5. https://doi.org/10.1128/IAI.61.5.2211-2215.1993Gotto JW, Eckhardt T, Reilly PA, Scott JV, Cowell JL, Metcalf TN, 3rd, et al. Biochemical and immunological properties of two forms of pertactin, the 69,000-molecular-weight outer membrane protein of Bordetella pertussis. Infect Immun. 1993;61(5):2211–5. https://doi.org/10.1128/IAI.61.5.2211-2215.1993Jennings HJ, Ługowski C, Ashton FE. Conjugation of meningococcal lipopolysaccharide R-type oligosaccharides to tetanus toxoid as route to a potential vaccine against group B Neisseria meningitidis. Infect Immun. 1984.43(1):407–12. https://doi.org/10.1128/IAI.43.1.407-412.1984Jennings HJ, Ługowski C, Ashton FE. Conjugation of meningococcal lipopolysaccharide R-type oligosaccharides to tetanus toxoid as route to a potential vaccine against group B Neisseria meningitidis. Infect Immun. 1984.43(1):407–12. https://doi.org/10.1128/IAI.43.1.407-412.1984Dias WO, van der Ark AA, Sakauchi MA, Kubrusly FS, Prestes AF, Borges MM, et al. An improved whole cell pertussis vaccine with reduced content of endotoxin. Hum Vaccin Immunother. 2013;9(2):339–48. https://doi.org/10.4161/hv.22847Dias WO, van der Ark AA, Sakauchi MA, Kubrusly FS, Prestes AF, Borges MM, et al. An improved whole cell pertussis vaccine with reduced content of endotoxin. Hum Vaccin Immunother. 2013;9(2):339–48. https://doi.org/10.4161/hv.22847Mohammadpour Dounighi N, Razzaghi-Abyane M, Nofeli M, Zolfagharian H, Shahcheraghi F. Study on toxicity reduction and potency induction in whole-cell pertussis vaccine by developing a new optimal inactivation condition processed on Bordetella pertussis. Jundishapur J Microbiol. 2016;9(7):e34153. https://doi.org/10.5812/jjm.34153Mohammadpour Dounighi N, Razzaghi-Abyane M, Nofeli M, Zolfagharian H, Shahcheraghi F. Study on toxicity reduction and potency induction in whole-cell pertussis vaccine by developing a new optimal inactivation condition processed on Bordetella pertussis. Jundishapur J Microbiol. 2016;9(7):e34153. https://doi.org/10.5812/jjm.34153Чупринина РП, Алексеева ИА. Возможность повышения иммуногенной активности и стабильности цельноклеточного коклюшного компонента комбинированных вакцин. Эпидемиология и вакцинопрофилактика. 2014;2(75):89–95.Chuprinina RP, Alekseeva IA. The possibility of increasing the potency and stability of whole-cell pertussis component of combined vaccines. Epidemiologiya i vaktsinoprofilaktika = Epidemiology and Vaccinal Prevention. 2014;2(75):89–95 (In Russ.)

The authors declare that there are no conflicts of interest present.