Improvement of the process of production of polysaccharide polyribosyl ribitol phosphate used in the Haemophilus influenzae vaccines
https://doi.org/10.47183/mes.2021.037
Abstract
The production of vaccines requires constant improvement of methods and tools, revision and modernization of the current technology with the aim to improve quality of the product made for the benefit of public health. The purposяe of this work was to improve the process of production of polysaccharide polyribosyl ribitol phosphate (PRP), which is the active agent of Haemophilus influenzae type b (Hib) vaccines. We investigated how PRP yield depends on the following factors: concentration of dissolved oxygen in the culture liquid, glucose concentration control method applied in cultivation, source of protein for the producer microorganism, stability of the polysaccharide at the culture liquid inactivation stage. As a result, we managed to increase the PRP yield in the culture liquid by 10%, ensured a 25% boost of the biomass accumulation rate during cultivation in the fermenter and reduced the cultivation time by 6.5 hours. The PRP loss rate at the culture liquid inactivation stage was reduced by 80%. Relying on the patented composition, we invented a new composition of the nutrient medium that meets the current regulatory requirements.
About the Authors
A. A. BelyankinRussian Federation
52, Svobody str., St. Petersburg, 198320.
E. L. Salimova
Russian Federation
52, Svobody str., St. Petersburg, 198320.
A. D. Konon
Russian Federation
52, Svobody str., St. Petersburg, 198320.
V. P. Trukhin
Russian Federation
52, Svobody str., St. Petersburg, 198320.
References
1. Baranov AA, i dr. Vakcinoprofilaktika gemofil'noj infekcii tipa b. M., 2020; 33 s. (In Russian).
2. Lobzin YuV. Upravljaemye i social'no znachimye infekcii: problemy i puti reshenija. Bjulleten' medicinskoj nauki. 2019; 3 (15): 39–43.
3. Sivaja OV, Kozlov RS, Krechikova OI, Ivanchik NV, Katosova LK, Gudkova LV. Antibiotikorezistentnost' Haemophilus influenzae v Rossii: rezul'taty mnogocentrovogo prospektivnogo issledovanija PeGAS. Klinicheskaja mikrobiologija i antimikrobnaja himioterapija. 2014; (1): 57–69. (In Russian).
4. Strachunskij LS, Belousov YuB, Kozlov SN, redaktory. Prakticheskoe rukovodstvo po antiinfekcionnoj himioterapii. Smolensk, 2007; 464 s. (In Russian).
5. Koroleva IS, Koroleva MA, Melnikova AA. Jepidemiologija gnojnyh bakterial'nyh meningitov v period vakcinoprofilaktiki pnevmokokkovoj i gemofil'noj infekcij v Rossijskoj Federacii. Jepidemiologija i infekcionnye bolezni. Aktual'nye voprosy. 2017; (6): 63–8. (In Russian).
6. Fedoseenko MV, Galickaya MG, Namazova LS. Jepoha kon"jugirovannyh vakcin: mezhdunarodnyj opyt uspeshnogo primenenija. Pediatricheskaja farmakologija. 2008; 6: 6–14. (In Russian).
7. Granoff D. Haemophilus influenzae type b polysaccharide vaccines. The Journal of Pediatrics. 1985; 107 (3): 330–6.
8. Weekly epidemiological record. Haemophilus influenzae type b (Hib) Vaccination Position Paper — September 2013. 2013; 88 (39): 413–28.
9. World Health Organization Recommendations for the production and control of Haemophilus influenzae type b conjugate vaccines. WHO Technical Report Series. 2000; 897: 27–60.
10. European Pharmacopoeia 8.0. Council of Europe, Strasbourg, 2014. V. 1; 1380 p.
11. Vakcina gemofil'naja tip b kon"jugirovannaja, liofilizat dlja prigotovlenija rastvora dlja vnutrimyshechnogo vvedenija. Gosudarstvennaja farmakopeja RF XIV izd. Tom 4. FS.3.3.1.0055.18. Dostupno po ssylke: http://femb.ru/femb/pharmacopea.php (data obrashhenija: 16.02.2020). (In Russian).
12. OFS.1.2.3.0019.15. Opredelenie saharov spektrofotometricheskim metodom. Federal'naja jelektronnaja medicinskaja biblioteka. Dostupno po ssylke: http://www.femb.ru/feml (data obrashhenija: 31.04.2020). (In Russian).
13. Riza A. Isolation and purification of capsular polysaccharide of Haemophilus influenzae type b (Hib) by hexadecyltrimethylammonium bromide (CTAB) precipitation and chromatography. In: Riza A, Nurainy N, editors. Proceed Intern Semin Chemist. 2008: 294–6.
14. Konon A. D. i dr. Optimizacija metodiki opredelenija koncentracii poliribozilribitolfosfata v processe proizvodstva substancii dlja polisaharidnyh vakcin. Innovacii v zdorov'e nacii. 2017: 194–8. (In Russian).
15. Truhin VP, Salimova EL, Konon AD, avtory; Shtamm Haemophilus influenzae SPB tip v — vysokoaktivnyj producent kapsul'nogo polisaharida poliribozilribitolfosfata. Patent RF # 2624014. 06.30.2017. (In Russian).
16. Truhin VP, Salimova EL, Konon AD, avtory; Sposob poluchenija vakciny gemofil'noj tip b kon"jugirovannoj. Patent RF #: 2704452. 28.10.2019. (In Russian).
17. Orlova OE, Yastrebova NE, Elkina SI. Specificheskie harakteristiki sostava pitatel'noj sredy dlja kul'tivirovanija Haemophilis influenzae tip b s tochki zrenija bakterial'nogo metabolizma. Zhurnal mikrobiologii, jepidemiologii i immunobiologii. 2001; 3: 111–7. (In Russian).
18. Esmaily F, Aminian M, Tavangar AR, Hadi A, editors. Comparison of bacterial biomass and PRP production between different isolates of Haemophilus influenzae type b (Hib) under different culture conditions. Archives of Razi Institute. 2011; 66: 43–49.
19. Orlova OE, i dr. Kul'tivirovanie Haemophilus influenzae, serotipa B, v amino-peptidnoj polusinteticheskoj pitatel'noj srede. Zhurnal mikrobiologii, jepidemiologii i immunobiologii. 2001; 3: 56–8. (In Russian).
20. Loeb MR. Ferrochelatase activity and protoporphyrin IX utilization in Haemophilus influenza. Journal of bacteriology. 1995; 177 (12): 3613–15.
21. Beri S, Gandhi D, Sharma P, Gundpatil D, Goel S, Gairola S. Comparability studies of hemin from two different origins porcine and bovine in the production of Haemophilus influenzae type b (Hib) polysaccharide. Biologicals. 2020; 67: 38–41. DOI: 10.1016/j.biologicals.2020.07.006. PMID: 32768281.
22. de Oliveira Cintra F, Takagi M. Study of the chemical stability of the capsular polysaccharide produced by Haemophilus influenzae type b. Carbohydrate polymers. 2015; 116: 167–72.
23. Orlova OE, i dr. Dinamika rosta Haemophilus influenzae serotipa B i sintez kapsul'nogo polisaharida v processe kul'tivirovanija v sinteticheskoj pitatel'noj srede. Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2001; 2: 75. (In Russian).
Review
For citations:
Belyankin A.A., Salimova E.L., Konon A.D., Trukhin V.P. Improvement of the process of production of polysaccharide polyribosyl ribitol phosphate used in the Haemophilus influenzae vaccines. Extreme Medicine. 2021;23(4):5-11. https://doi.org/10.47183/mes.2021.037