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ISSN 1027-2852 (Electronic)
ISSN 0864-4551 (Print)

2013, Number 3

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Biotecnol Apl 2013; 30 (3)

Procedure for the conjugation of the Streptococcus pneumoniae serotype 6B capsular polysaccharide to the tetanus toxoid

Soubal JP, Peña L, Santana D, Valdés Y, García D, Pedroso J, Cardoso F, González H, Fernández V, Vérez V

Language: Spanish
References: 39
Page: 199-215
PDF size: 272.93 Kb.


ABSTRACT

Streptococcus pneumoniae causes annually 826 000 deaths in children under five years. The serotype 6B, one of higher incidence, is targeted by the Cuban research and development project to develop a conjugate vaccine. There is limited data on how modifications caused by conjugation affect the physicochemical and antigenic characteristics of polysaccharides, particularly for serotype 6B capsular polysaccharide (PS6B), despite being the least immunogenic among S. pneumoniae polysaccharides. In this work, a conjugation procedure was established for PS6B comprising: fragmentation by acid hydrolysis, activation by periodate oxidation, and conjugation to tetanus toxoid (TT) by reductive amination to increase its immunogenicity. Reaction conditions were set to obtain the polysaccharide in three molecular size ranges (1-10, 10-30, 30-100 kDa) and levels of oxidation. PS6B fragmentation below 10 kDa and oxidation above 24 % of the repetitive units implied the loss of antigenicity. Polysaccharide length but not oxidation level had an impact on the physicochemical characteristics of the conjugates in the tested conditions. Unlike the native polysaccharide, conjugated 10-30 kDa and 30-100 kDa PS6B were immunogenic in rabbits, with evidence of thymus-dependent response. The procedure described supports obtaining PS6B-TT conjugates reproducibly in the 30- 100 kDa and 10-30 kDa molecular size ranges and with 8-18 % oxidized repeat units, which are immunogenic.


REFERENCES

  1. O’Brien KL, Wolfson LJ, Watt JP, Henkle E, Deloria-Knoll M, McCall N, et al. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet. 2009; 374(9693):893-902.

  2. González-Fernández A, Faro J, Fernández C. Immune renponses to polysaccharides: Lessons from humans and mice. Vaccine. 2008;26:292-300.

  3. Lucas AH, Rittenhouse-Olson K, Kronenberg M, Apicella MA, Wang D, Schreiber JR, et al. Carbohydrate moieties as vaccine candidates: Meeting summary. Vaccine. 2010;28(4):1121-31.

  4. Overturf GD. American Academy of Pediatrics. Committee on Infectious Diseases. Technical report: prevention of pneumococcal infections, including the use of pneumococcal conjugate and polysaccharide vaccines and antibiotic prophylaxis. Pediatrics. 2000;106(2 Pt 1):367-76.

  5. Organización Panamericana de la Salud. Informe Regional de SIREVA II: datos por país y por grupos de edad sobre las características de los aislamientos de Streptococcus pneumoniae, Haemophilus influenzae y Neisseria meningitidis en procesos invasores, 2000-2005. Documentos Técnicos. Tecnologías Esenciales de Salud. THS/EV-2007/002.

  6. Rodgers GL, Arguedas A, Cohen R, Dagan R. Global serotype distribution among Streptococcus pneumoniae isolates causing otitis media in children: Potential implications for pneumococcal conjugate vaccines. Vaccine. 2009;27:3802-10.

  7. Oosterhuis-Kafeja F, Beutels P, Van Damme P. Immunogenicity, effi cacy, safety and effectiveness of pneumococcal conjugate vaccines (1998-2006). Vaccine. 2007; 25(12):2194-212.

  8. Rückinger S, Dagan R, Albers L, Schönberger K, von Kries R. Immunogenicity of pneumococcal conjugate vaccines in infants after two or three primary vaccinations: a systematic review and metaanalysis. Vaccine. 2011;29(52):9600-6.

  9. Kenne L, Lindberg B, Madden J. Structural studies of the capsular antigen from Streptococcus pneumonia Type 26. Carbohydr Res. 1979;73:175-82.

  10. Sun Y, Park MK, Diamond B, Solomon A, Nahm MH. Repertoire of human antibodies against the polysaccharide capsule of Streptococcus pneumoniae serotype 6B. Infect Immun. 1999;67:1172-9.

  11. Peeters CC, Lagerman PR, de Weers O, Oomen LA, Hoogerhout P, Beurret M, et al. Preparation of polysaccharideconjugate vaccines. Methods Mol Med. 2003;87:153-74.

  12. Brückner J. Estimation of monosaccharides by the orcinol-sulphuric acid reaction. Biochem J. 1955;60(2):200-5.

  13. Porro M, Viti S, Antoni G, Neri P. Modifi cations of the Park-Johnson Ferricyanide submicromethod for the assay of reducing groups in carbohydrates. Anal Biochem. 1981;118:301-6.

  14. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193:265-75.

  15. van Dam JE, Breg J, Komen R, Kamerling JP, Vliegenthart JF. Isolation and structural studies of phosphate-containing oligosaccharides from alkaline and acid hydrolysates of Streptococcus pneumoniae type 6B capsular polysaccharide. Carbohydr Res. 1989;187(2):267-86.

  16. Chang J, Serrano Y, Garrido R, Rodríguez LM, Pedroso J, Cardoso F, et al. Relevance of O-acetyl and phosphoglycerol groups for the antigenicity of Streptococcus pneumoniae serotype 18C capsular polysaccharide. Vaccine. 2012; 30(49):7090-6.

  17. Anttila M, Eskola J, Ahman H, Käyhty H. Avidity of IgG for Streptococcus pneumoniae type 6B and 23F polysaccharides in infants primed with pneumococcal conjugates and boosted with polysaccharide or conjugate vaccines. J Infect Dis. 1998; 177(6):1614-21.

  18. Abeygunawardana C, Williams TC, Summer JS, Hennessey JP. Development and validation of an NMR-based identity assay for bacterial polysaccharides. Anal Biochem. 2000;279:226-40.

  19. Kamerling J. Pneumococcal Polysaccharides: A Chemical View. In: Streptococcus pneumoniae. Molecular biology & mechanisms of disease. New York: Mary Ann Liebert, Inc.; 1999. p.81-112.

  20. Hausdorff WP, Siber JR, Paradiso PR, inventors; Wyeth Lederley, Inc., assignee. Multivalent pneumococcal polysaccharideprotein conjugate composition. US patent US 0130137. 2009 may 21.

  21. Bröker M, Dull PM, Rappuoli R, Costantino P. Chemistry of a new investigational quadrivalent meningococcal conjugate vaccine that is immunogenic at all ages. Vaccine. 2009;27:5574-80.

  22. Rodríguez ME, van den Dobbelsteen GP, Oomen LA, de Weers O, van Buren L, Beurret M, et al. Immunogenicity of Streptococcus pneumoniae type 6B and 14 polysaccharide-tetanus toxoid conjugates and the effect of uncoupled polysaccharide on the antigen-specifi c immune response. Vaccine. 1998;16(20):1941-9.

  23. Wessels MR, Muñoz A, Kasper DL. A model of high-affi nity antibody binding to type III group B Streptococcus capsular polysaccharide. Proc Natl Acad Sci USA. 1987;84(24):9170-4.

  24. Zou W, Mackenzie R, Thérien L, Hirama T, Yang Q, Gidney MA, et al. Conformational epitope of the type III group B Streptococcus capsular polysaccharide. J Immunol. 1999;163(2):820-5.

  25. Moore SL, Uitz C, Ling CC, Bundle DR, Fusco PC, Michon F. Epitope specifi cities of the group Y and W-135 polysaccharides of Neisseria meningitidis. Clin Vaccine Immunol. 2007;14(10):1311-7.

  26. Wessels MR, Kasper DL. Antibody Recognition of the type 14 pneumococcal capsule. evidence of conformational epitope in a neutral polysaccharide. J Exp Med. 1989;169(6): 2121-31.

  27. Mawas F, Niggemann J, Jones C, Corbel MJ, Kamerling JP, Vliegenthart JF. Immunogenicity in a mouse model of a conjugate vaccine made with a synthetic single repeating unit of type 14 pneumococcal polysaccharide coupled to CRM197. Infect Immun. 2002; 70(9):5107-14.

  28. Laferriere CA, Sood RK, de Muys JM, Michon F, Jennings HJ. Streptococcus pneumoniae type 14 polysaccharide-conjugate vaccines: length stabilization of opsonophagocytic conformational polysaccharide epitopes. Infect Immun. 1998;66(6):2441-6.

  29. Kim JS, Laskowich ER, Michon F, Kaiser RE, Arumugham RG. Monitoring activation sites on polysaccharides by GC-MS. Anal Biochem. 2006;358(1):136-42.

  30. Gudlavalleti SK, Lee CH, Norris SE, Paul- Satyaseela S, Vann WF, Frasch CE. Comparison of Neisseria meningitidis serogroup W135 polysaccharide-tetanus toxoid conjugate vaccines made by periodate activation of O-acetylated, non-O-acetylated and chemically de-O-acetylated polysaccharide. Vaccine. 2007;25(46):7972-80.

  31. Wessels MR, Paoletti LC, Guttormsen HK, Michon F, D’Ambra AJ, Kasper DL. Structural properties of group b streptococcal type III polysaccharide conjugate vaccines that infl uence immunogenicity and effi cacy. Infect Immun. 1998;66(5):86-2192.

  32. Michon F, Uitz C, Sarar A, D’Ambra AJ, Laude-Sharp M, Moore S, Fusco PC. Group B Streptococcal Type II and III Conjugate Vaccines. Physicochemical Properties that Infl uence Immunogenicity. Clin Vaccine Immunol. 2006;13(18):936-43.

  33. Wuorimaa T, Dagan R, Väkeväinen M, Bailleux F, Haikala R, Yaich M, et al. Avidity and subclasses of IgG after immunization of infants with an 11-valent pneumococcal conjugate vaccine with or without aluminum adjuvant. J Infect Dis. 2001;184(9):1211-5.

  34. Usinger WR, Lucas AH. Avidity as a determinant of the protective effi cacy of human antibodies to pneumococcal capsular polysaccharides. Infect Immun. 1999;67:2366-70.

  35. Daum RS, Hogerman D, Rennels MB, Bewley K, Malinoski F, Rothstein E, et al. Infant immunization with pneumococcal CRM197 vaccines: effect of saccharide size on immunogenicity and interactions with simultaneously administered vaccines. J Infect Dis. 1997; 176(2):445-55.

  36. An SJ, Yeon YK, Kothari S, Kothari N, Kim JA, Lee E, et al. Physico-chemical properties of Salmonella typhi Vi polysaccharide-diftheria toxoid conjugate vaccines affect immunogenicity. Vaccine. 2011;29(44):7618-23.

  37. Dick WE Jr, Beurret M. Glycoconjugates of bacterial carbohydrate antigens. A survey and considerations of design and preparation factors. Contrib Microbiol Immunol. 1989; 10:48-114.

  38. Laferrière CA, Sood RK, de Muys JM, Michon F, Jennings HJ. The synthesis of Streptococcus pneumoniae polysaccharide-tetanus toxoid conjugates and the effect of chain length on immunogenicity. Vaccine. 1997; 5(2):179-86.

  39. Mäkelä O, Péterfy F, Outschoorn IG, Richter AW, Seppälä I. Immunogenic properties of alpha (1→6) dextran, its protein conjugates, and conjugates of its breakdown products in mice. Scand J Immunol. 1984;19(6):541-50.




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