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Pediatric Drugs

, Volume 11, Issue 5, pp 349–357 | Cite as

Pneumococcal Polysaccharide Protein D-Conjugate Vaccine (Synflorix™; PHiD-CV)

  • Jamie D. CroxtallEmail author
  • Gillian M. Keating
Adis Drug Profile

Abstract

  • ▲ The pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV; Synflorix™) contains ten capsular polysaccharide serotypes from the bacterium Streptococcus pneumoniae, eight of which are conjugated to a nonlipidated cell-surface liporotein (protein D) of non-typeable Haemophilus influenzae (NTHi) and two of which are conjugated to either tetanus or diphtheria toxoid.

  • ▲ In a three-dose primary vaccination schedule in infants aged <6 months, PHiD-CV elicited high immune responses against all pneumococcal serotypes contained in the vaccine and was non-inferior to an approved 7-valent pneumococcal conjugate vaccine (7vCRM) for eight of the ten serotypes (five of the seven common to both vaccines). Moreover, functional antibodies were elicited against all vaccine serotypes in an opsonophagocytic activity (OPA) assay.

  • ▲ A fourth booster dose of PHiD-CV during the second year of life elicited an anamnestic response against all ten pneumococcal serotypes, as determined by both antibody concentrations and OPA titers.

  • ▲ There were no clinically relevant changes in the immunogenicity of PHiD-CV when coadministered with meningococcal serogroup C conjugate or pentavalent whole cell pertussis combination vaccines, and polio vaccines using two different primary vaccination schedules.

  • ▲ 11Pn-PD, an 11-valent prototype of PHiD-CV, demonstrated protection against episodes of acute otitis media (AOM) caused by S. pneumoniae and NTHi in infants aged <27 months. The first occurrence of an episode of AOM caused by pneumococcal vaccine serotypes was reduced by 52.6% in 11Pn-PD vaccinees compared with recipients of a control vaccine (primary endpoint).

  • ▲ The tolerability profile of PHiD-CV was generally similar to that of 7vCRM.

Keywords

Acute Otitis Medium Invasive Pneumococcal Disease Protective Efficacy Pneumococcal Vaccine Booster Vaccination 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments and Disclosures

This manuscript was reviewed by: H. Käyhty, National Institute for Health and Welfare, Department of Vaccination and Immune Protection Response Unit, Helsinki, Finland; M. Knuf, Johannes Gutenberg University, Mainz, Germany; R. Prymula, Department of Epidemiology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. This included review and comment by Lode Schuerman, GlaxoSmithKline Biologicals. Changes resulting from comments received were made on the basis of scientific and editorial merit.

References

  1. 1.
    Hausdorff W, Bryant J, Kloek C, et al. The contribution of specific pneumococcal serogroups to different disease manifestations: implications for conjugate vaccine formulation and use, part II. Clin Infect Dis 2000; 30(1): 122–40PubMedCrossRefGoogle Scholar
  2. 2.
    Hausdorff WP, Bryant J, Paradiso PR. Which pneumococcal serogroups cause the most invasive disease: implications for conjugate vaccine formulation and use, part I. Clin Infect Dis 2000 Jan; 30(1): 100–21PubMedCrossRefGoogle Scholar
  3. 3.
    Foxwell A, Kyd J, Cripps A. Nontypeable Haemophilus influenzae: pathogenesis and prevention. Microbiol Mol Biol Rev 1998; 62(2): 294–308PubMedGoogle Scholar
  4. 4.
    World Health Organization. Haemophilus influenzae type B (Hib) [online]. Available from URL: http://www.who.int/mediacentre/factsheets/fs294/enindex.html [Accessed 2009 May 5]
  5. 5.
    Giebink G. The prevention of pneumococcal disease in children. N Engl J Med 2001; 345(16): 1177–83PubMedCrossRefGoogle Scholar
  6. 6.
    World Health Organization. Immunization, vaccines and biologicals [online]. Available from URL: http://who.int/vaccines/enpneumococcus.shtml [Accessed 2009 May 5]
  7. 7.
    Cripps AW, Otczyk DC, Kyd JM. Bacterial otitis media: a vaccine preventable disease? Vaccine 2005 Mar 18; 23(17–18): 2304–10PubMedCrossRefGoogle Scholar
  8. 8.
    Erramouspe J, Heyneman C. Treatment and prevention of otitis media. Ann Pharmacother 2000; 34(12): 1452–68PubMedCrossRefGoogle Scholar
  9. 9.
    University of Michigan Health System. Otitis media: guidelines for clinical care [online]. Available from URL: http://cme.med.umich.edu/pdf/guideline/OM07.pdf [Accessed 2009 May 6]
  10. 10.
    Forsgren A, Riesbeck K, Janson H. Protein D of Haemophilus influenzae: a protective nontypeable H. influenzae antigen and a carrier for pneumococcal conjugate vaccines. Clin Infect Dis 2008 Mar 1; 46(5): 726–31PubMedCrossRefGoogle Scholar
  11. 11.
    Stein K. Thymus-independent and thymus-dependent responses to polysaccharide antigens. J Infect Dis 1992; 165Suppl. 1: S49–52PubMedCrossRefGoogle Scholar
  12. 12.
    Murphy TF. Respiratory infections caused by non-typeable Haemophilus influenzae. Curr Opin Infect Dis 2003 Apr; 16(2): 129–34PubMedCrossRefGoogle Scholar
  13. 13.
    Dhillon S, Keam S. DTaP-IPV/Hib vaccine (Pentacel®). Pediatr Drugs 2008; 10(6): 405–16CrossRefGoogle Scholar
  14. 14.
    Maryland Department of Health & Mental Hygiene. Haemophilus influenzae type b (Hib) fact sheet [online]. Available from URL: http://www.edcp.org/pdf_factsheets/Haemophilus_influenzae_type-b.pdf [Accessed 2009 May 5]
  15. 15.
    Darkes MJ, Plosker GL. Pneumococcal conjugate vaccine (Prevnar; PNCRM7): a review of its use in the prevention of Streptococcus pneumoniae infection. Paediatr Drugs 2002; 4(9): 609–30PubMedGoogle Scholar
  16. 16.
    Whitney C, Farley M, Hadler J, et al. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med 2003; 348(18): 1737–46PubMedCrossRefGoogle Scholar
  17. 17.
    Feavers I, Knezevic I, Powell M, et al. Challenges in the evaluation and licensing of new pneumococcal vaccines, 7–8 July 2008, Ottawa, Canada. Vaccine 2009; 27(28): 3681–8PubMedCrossRefGoogle Scholar
  18. 18.
    World Health Organization. WHO/Health Canada consultation on serological criteria for evaluation and licensing of new pneumococcal vaccines [online]. Available from URL: http://www.who.int/biologicals/publications/meetings/areas/vaccines/pneumococcal/en/index.html [Accessed 2009 Apr 21]
  19. 19.
    Prymula R, Peeters P, Chrobok V, et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. Lancet 2006 Mar 4; 367(9512): 740–8PubMedCrossRefGoogle Scholar
  20. 20.
    Toropainen M, Raitolehto A, Henckaerts I, et al. Pneumococcal Haemophilus influenzae protein D conjugate vaccine induces antibodies that inhibit glycerophosphodiester phosphodiesterase activity of protein D. Infect Immun 2008 Oct; 76(10): 4546–53PubMedCrossRefGoogle Scholar
  21. 21.
    Nurkka A, Joensuu J, Henckaerts I, et al. Immunogenicity and safety of the eleven valent pneumococcal polysaccharide-protein D conjugate vaccine in infants. Pediatr Infect Dis J 2004 Nov; 23(11): 1008–14PubMedCrossRefGoogle Scholar
  22. 22.
    Poolman J, Kriz P, Feron C, et al. Pneumococcal serotype 3 otitis media, limited effect of polysaccharide conjugate immunisation and strain characteristics. Vaccine 2009; 27(24): 3213–22PubMedCrossRefGoogle Scholar
  23. 23.
    Schuerman L, Prymula R, Chrobok V, et al. Kinetics of the immune response following pneumococcal PD conjugate vaccination. Vaccine 2007 Mar 1; 25(11): 1953–61PubMedCrossRefGoogle Scholar
  24. 24.
    European Medicines Agency. Synflorix, pneumococcal polysaccharide conjugate vaccine (adsorbed): summary of product characteristics [online]. Available from URL: http://ec.europa.eu/enterprise/pharmaceuticals/register/2009/200903305561l/anx_5561l_en.pdf [Accessed 2009 Apr 22]
  25. 25.
    Vesikari T, Wysocki J, Chevallier B, et al. Immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) compared to the licensed 7vCRM vaccine. Pediatr Infect Dis J 2009 Apr; 28(4): S66–76PubMedGoogle Scholar
  26. 26.
    Wysocki J, Tejedor CC, Grunert D, et al. Immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when coadministered with different Neisseria meningitidis serogroup C conjugate vaccines. Pediatr Infect Dis J 2009 Apr; 28(4): S77–88PubMedGoogle Scholar
  27. 27.
    Bermal N, Szenborn L, Chrobot A, et al. The 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) coadministered with DTPw-HBV/Hib and poliovirus vaccines: assessment of immunogenicity. Pediat Infect Dis J 2009 Apr; 28(4): S89–96CrossRefGoogle Scholar
  28. 28.
    Knuf M, Szenborn L, Moro M, et al. Immunogenicity of routinely used childhood vaccines when coadministered with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Pediat Infect Dis J 2009 Apr; 28(4): S97–108CrossRefGoogle Scholar
  29. 29.
    Chevallier B, Vesikari T. Safety and reactogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when coadministered with route childhood vaccines. Ped Infect Dis J 2009 Apr; 28(4): Sl09–18Google Scholar
  30. 30.
    European Medicines Agency. Assessment report for synflorix [online]. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/synflorix/H-973-en6.pdf [Accessed 2009 Jun 3]
  31. 31.
    Henckaerts I, Goldblatt D, Ashton L, et al. Critical differences between pneumococcal polysaccharide enzyme-linked immunosorbent assays with or without 22F inhibition at low antibody concentrations in paediatric sera. Clin Vaccine Immunol 2006; 13(3): 356–60PubMedCrossRefGoogle Scholar
  32. 32.
    Schuerman L, Prymula R, Henckaerts I, et al. ELISA IgG concentrations and opsonophagocytic activity following pneumococcal protein D conjugate vaccination and relationship to efficacy against acute otitis media. Vaccine 2007 Mar 1; 25(11): 1962–8PubMedCrossRefGoogle Scholar
  33. 33.
    Henckaerts I, Durant N, De Grave D, et al. Validation of a routine opsonophagocytosis assay to predict invasive pneumococcal disease efficacy of conjugate vaccine in children. Vaccine 2007; 25(13): 2518–27PubMedCrossRefGoogle Scholar
  34. 34.
    Romero-Steiner S, Libutti D, Pais LB, et al. Standardization of an opsonophagocytic assay for the measurement of functional antibody activity against Streptococcus pneumoniae using differentiated HL-60 cells. Clin Diagn Lab Immunol 1997; 4(4): 415–22PubMedGoogle Scholar
  35. 35.
    Hausdorff WP, Beckers F, Dagan R, et al. Estimation of the direct impact of a 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) candidate against invasive pneumococcal disease (IPD). 6th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD); 2008 Jun 8–12 June; ReykjavikGoogle Scholar

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Adis, a Wolters Kluwer BusinessMairangi Bay, North Shore 0754, AucklandNew Zealand

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