Immunobiological properties of circulating Bordetella pertussis strains: Candidate strains for production of pertussis vaccines
https://doi.org/10.30895/2221-996X-2025-25-4-428-437
Abstract
INTRODUCTION. One of the reasons for increased pertussis cases is the pathogen adapting to the existing collective immunity formed under conditions of vaccine prophylaxis. Monitoring immunobiological properties of Bordetella pertussis strains is necessary to track changes in the pathogen adaptive potential triggered by vaccination.
AIM. This study aimed to compare immunobiological properties of isolated circulating Bordetella pertussis strains and strains used to produce whole-cell pertussis vaccine.
MATERIALS AND METHODS. The study used nine isolates of modern circulating strains of B. pertussis. Experimental series of whole-cell pertussis vaccine was made using strains isolated from the patients with pertussis in 2016–2020. The series was evaluated by the following parameters: serological properties and antigenic structure (serotypes); haemagglutinating, haemolytic, and dermonecrotic effect; virulence; residual toxicity and protective properties. The study used outbred and inbred F1 mice (C57Bl/6J×CBA) and evaluated morphological and cultural properties of the bacteria. Experimental data were compared with the requirements for production strains set out in the local guidelines MUK 4.2.2317-08 (Selection, testing and storage of production strains of pertussis, parapertussis and bronchisepticosis bacteria).
RESULTS. Strains 16-16 and 33-18 were obtained from nine isolates of circulating B. pertussis strains meeting the requirements for production strains. The assessment results of protective activity for strains 25-16, 37-18, and 2-20 were analysed and showed the necessity of further confirming this value due to the limited experimental material. Four B. pertussis strains, 31(2)-17, 28(1)-18, 25-16, and 2-20, did not show the required protective activity (<8 IU/mL).
CONCLUSIONS. The properties of isolates 16-16 and 33-18 of B. pertussis meet all the requirements for production strains. The test strains have a modern genotype and are prospectively applicable as candidates for replacing obsolete B. pertussis strains in production of pertussis vaccines.
Keywords
About the Authors
I. A. AlekseevaRussian Federation
Irina A. Alekseeva, Dr. Sci. (Med.)
8/2 Petrovsky Blvd, Moscow 127051
D. N. Lepikhova
Russian Federation
Darya N. Lepikhova
8/2 Petrovsky Blvd, Moscow 127051
O. Yu. Borisova
Russian Federation
Olga Yu. Borisova, Dr. Sci. (Med.), Prof.
10 Admiral Makarov St., Moscow 125212
A. S. Pimenova
Russian Federation
Alena S. Pimenova, Cand. Sci. (Med.)
10 Admiral Makarov St., Moscow 125212
I. Yu. Andrievskaya
Russian Federation
Irina Yu. Andrievskaya
10 Admiral Makarov St., Moscow 125212
I. V. Ibragimkhalilova
Russian Federation
Ilkhamya V. Ibragimkhalilova, Cand. Sci. (Biol.)
8/2 Petrovsky Blvd, Moscow 127051
References
1. Babachenko IV, Nesterova YuV, Chernyshova YuYu, et al. Clinical-epidemiological aspects of whooping cough in children in conditions of mass vaccinoprophylactics. Journal Infectology. 2019;11(2):88–96 (In Russ.). https://doi.org/10.22625/2072-6732-2019-11-2-88-96
2. Krasnov VV, Ilyanenkov KF, Pavlovich LR, Kuzmicheva MV. Pertussis in infants. Children Infections. 2018;1(1):12–7 (In Russ.). https://doi.org/10.22627/2072-8107-2018-17-1-12-17
3. Esposito S, Stefanelli P, Fry NK, et al. Pertussis prevention: Reasons for resurgence, and differences in the current acellular pertussis vaccines. Front Immunol. 2019;10:1344. https://doi.org/10.3389/fimmu.2019.01344
4. Mir-Cros A, Moreno-Mingorance A, Martin-Gomez MT, et al. Pertactin-deficient Bordetella pertussis with unusual mechanism of pertactin disruption, Spain, 1986–2018. Emerg Infect Dis. 2022;28(5):967–76. https://doi.org/10.3201/eid2805.211958
5. Burns DL, Meade BD, Messionnier NE. Pertussis resurgence: Perspectives from the Working Group Meeting on pertussis on the causes, possible paths forward, and gaps in our knowledge. J Infect Dis. 2014;209(Suppl 1):S32–5. https://doi.org/10.1093/infdis/jit491
6. Mooi 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/S0950268813000071
7. Zomer A, Otsuka N, Hiramatsu Y, et al. Bordetella pertussis population dynamics and phylogeny in Japan after adoption of acellular pertussis vaccines. Microb Genom. 2018;4(5):e000180. https://doi.org/10.1099/mgen.0.000180
8. Mir-Cros A, Moreno-Mingorance A, Martín-Gómez MT, et al. Population dynamics and antigenic drift of Bordetella pertussis following whole cell vaccine replacement, Barcelona, Spain, 1986–2015. Emerg Microbes Infect. 2019;8(1):1711–20. https://doi.org/10.1080/22221751.2019.1694395
9. Ross PJ, Sutton CE, Higgins S, et al. Relative contribution of Th1 and Th17 cells in adaptive immunity to Bordetella pertussis: Towards the rational design of an improved acellular pertussis vaccine. PLoS Pathog. 2013;9(4):e1003264. https://doi.org/10.1371/journal.ppat.1003264
10. Warfel JM, Zimmerman LI, Merkel TJ. Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model. Proc Natl Acad Sci USA. 2014;111(2):787–92. https://doi.org/10.1073/pnas.1314688110
11. Borisova OYu, Gadua NT, Pimenova AS, et al. Structure of population of strains of the Bordetella pertussis in the Russia. Epidemiology and Vaccinal Prevention. 2016;15(4):22–8 (In Russ.). https://doi.org/10.31631/2073-3046-2016-15-4-22-28
12. Koide K, Yao SM, Chiang C-S, et al. Genotyping and macrolide-resistant mutation of Bordetella pertussis in East and South-East Asia. J Glob Antimicrob Resist. 2022;31:263–9. https://doi.org/10.1016/j.jgar.2022.10.007
13. Barkoff AM, Mertsola J, Pierard D, et al. Surveillance of circulating Bordetella pertussis strains in Europe during 1998 to 2015. J Clin Microbiol. 2018;56(5):e01998-17. https://doi.org/10.1128/JCM.01998-17
14. Moosa F, du Plessis M, Weigand MR, et al. Genomic characterization of Bordetella pertussis in South Africa, 2015–2019. Microb Genom. 2023;9(12):001162. https://doi.org/10.1099/mgen.0.001162
15. Fu P, Zhou J, Yang C, et al. Molecular evolution and increasing macrolide resistance of Bordetella pertussis, Shanghai, China, 2016–2022. Emerg Infect Dis. 2023;30(1):29–38. https://doi.org/10.3201/eid3001.221588
16. Weigand MR, Williams MM, Peng Y, et al. Genomic survey of Bordetella pertussis diversity, United States, 2000–2013. Emerg Infect Dis. 2019;25(4):780–3. https://doi.org/10.3201/eid2504.180812
17. Ma L, Caulfield A, Dewan KK, Harvill ET. Pertactin-deficient Bordetella pertussis, vaccine-driven evolution, and reemergence of pertussis. Emerg Infect Dis. 2021;27(6):1561–6. https://doi.org/10.3201/eid2706.203850
18. Belcher T, Preston A. Bordetella pertussis evolution in the (functional) genomics era. Pathog Dis. 2015;73(8):ftv064. https://doi.org/10.1093/femspd/ftv064
19. Borisova OYu, Andrievskaya IYu, Pimenova AS, et al. Genotypic characteristics of Bordetella pertussis, candidate strains for production of pertussis component of vaccines (statement I). Bulletin of RSMU. 2024;(2):4–9 (In Russ.). https://doi.org/10.24075/vrgmu.2024.017
20. Alekseeva IA, Lepikhova DN, Borisova OYu, et al. Influence of storage conditions on the toxicity of whole-cell pertussis vaccine in outbred mice. Biological Products. Prevention, Diagnosis, Treatment. 2025;25(1):111–20 (In Russ.). https://doi.org/10.30895/2221-996X-2025-25-1-111-120
21. Hiramatsu Y, Miyaji Y, Otsuka N, et al. Significant decrease in pertactin-deficient Bordetella pertussis isolates, Japan. Emerg Infect Dis. 2017;23(4):699–701. https://doi.org/10.3201/eid2304.161575
22. Kallonen T, Mertsola J, Mooi FR, He Q. Rapid detection of the recently emerged Bordetella pertussis strains with the ptxP3 pertussis toxin promoter allele by real-time PCR. Clin Microbiol Infect. 2012;18(9):E377–9. https://doi.org/10.1111/j.1469-0691.2012.04000.x
23. Petersen RF, Dalby T, Dragsted DM, et al. Temporal trends in Bordetella pertussis populations, Denmark, 1949–2010. Emerg Infect Dis. 2012;18(5):767–74. https://doi.org/10.3201/eid1805.110812
24. Schmidtke AJ, Boney KO, Martin SW, et al. Population diversity among Bordetella pertussis isolates, United States, 1935–2009. Emerg Infect Dis. 2012;18(8):1248–55. https://doi.org/10.3201/eid1808.120082
25. Mooi FR, van Loo IHM, van Gent M, et al. Bordetella pertussis strains with increased toxin production associated with pertussis resurgence. Emerg Infect Dis. 2009;15(8):1206–13. https://doi.org/10.3201/eid1508.081511
26. Carbonetti NH. Pertussis toxin and adenylate cyclase toxin: key virulence factors of Bordetella pertussis and cell biology tools. Future Microbiol. 2010;5(3):455–69. https://doi.org/10.2217/fmb.09.133
27. Pierce C, Klein N, Peters M. Is leukocytosis a predictor of mortality in severe pertussis infection? Intensive Care Med. 2000;26(10):1512–4. https://doi.org/10.1007/s001340000587
28. Advani A, Gustafsson L, Carlsson R-M, Donnelly D. Clinical outcome of pertussis in Sweden: association with pulsed-field gel electrophoresis profiles and serotype. APMIS. 2007;115(6):736–42. https://doi.org/10.1111/j.1600-0463.2007.apm_628.x
29. Basov AA, Vysochanskaya SO, Tsvirkun OV, et al. Criteria for assessing the epidemiological situation of pertussis in Russian Federation. Epidemiology and Vaccinal Prevention. 2024;23(1):4–13 (In Russ.). https://doi.org/10.31631/2073-3046-2024-23-1-4-13
30. Chodorowska M, Kuklinska D. Restrykcyjna analiza DNA paleczek Bordetella pertussis wyizolowanych od chorych na krztusiec w 1968 roku i w latach 1995–98 oraz szczepow B. pertussis stosowanych do produkcji krajowej szczepionki przeciwkrztuscowej. Med Dośw Mikrobiol. 2001;52(2):111–7 (In Polish).
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For citations:
Alekseeva I.A., Lepikhova D.N., Borisova O.Yu., Pimenova A.S., Andrievskaya I.Yu., Ibragimkhalilova I.V. Immunobiological properties of circulating Bordetella pertussis strains: Candidate strains for production of pertussis vaccines. Biological Products. Prevention, Diagnosis, Treatment. 2025;25(4):428-437. (In Russ.) https://doi.org/10.30895/2221-996X-2025-25-4-428-437




























