Advertisement

DTaP-IPV-HepB-Hib Vaccine (Hexyon®): An Updated Review of its Use in Primary and Booster Vaccination

  • Yahiya Y. SyedEmail author
Adis Drug Evaluation

Abstract

Hexyon® is a fully-liquid, ready-to-use, hexavalent vaccine approved in the EU since 2013 for primary and booster vaccination in infants and toddlers from age 6 weeks against diphtheria, tetanus, pertussis, hepatitis B (HB), poliomyelitis, and invasive diseases caused by Haemophilus influenzae type b (Hib). While the source of HB antigen in Hexyon® is different from other vaccines, the rest of its valences have been extensively used in other approved vaccines. Hexyon® is highly immunogenic for all its component toxoids/antigens when used as primary and booster vaccine in infants and toddlers, irrespective of vaccination schedule. It provides durable protection against hepatitis B. Hexyon® can be used for a mixed primary series of hexavalent-pentavalent-hexavalent vaccines or as a booster in infants primed with Infanrix hexa™ or pentavalent (whole-cell or acellular pertussis) vaccines. Coadministration of Hexyon® with other common childhood vaccines did not affect immune response to any vaccines. Hexyon® has a good reactogenicity/safety profile. The immunogenicity and safety profile of Hexyon® was similar to that of several approved vaccines, including Infanrix hexa™. However, Hexyon® offers the convenience of full-liquid, ready-to-use formulation, which may minimize vaccination errors and preparation time. Thus, Hexyon® is a convenient, useful option for vaccination against childhood diseases caused by six major pathogens.

Notes

Acknowledgements

During the review process, the manufacturer of Hexyon® was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Compliance with Ethical Standards

Funding

The preparation of this review was not supported by any external funding.

Conflicts of interest

Yahiya Syed is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

References

  1. 1.
    Obando-Pacheco P, Rivero-Calle I, Gomez-Rial J, et al. New perspectives for hexavalent vaccines. Vaccine. 2018;36(36):5485–94.CrossRefPubMedGoogle Scholar
  2. 2.
    Vidor E, Soubeyrand B. Manufacturing DTaP-based combination vaccines: industrial challenges around essential public health tools. Expert Rev Vaccines. 2016;15(12):1575–82.CrossRefPubMedGoogle Scholar
  3. 3.
    European Medicines Agency. Hexyon suspension for injection: summary of product characteristics. 2013. https://www.ema.europa.eu. Accessed 10 Jun 2019.
  4. 4.
    McCormack PL. DTaP-IPV-Hep B-Hib vaccine (Hexaxim®): a review of its use in primary and booster vaccination. Paediatr Drugs. 2013;15(1):59–70.CrossRefPubMedGoogle Scholar
  5. 5.
    Madhi SA, Lopez P, Zambrano B, et al. Antibody persistence in pre-school children after hexavalent vaccine infant primary and booster administration. Hum Vaccin Immunother. 2018;15(3):658–68.CrossRefGoogle Scholar
  6. 6.
    Vesikari T, Borrow R, Da Costa X, et al. Concomitant administration of a fully liquid ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal ACWY conjugate vaccine in toddlers. Vaccine. 2018;36(52):8019–27.CrossRefPubMedGoogle Scholar
  7. 7.
    Martinon-Torres F, Diez-Domingo J, Feroldi E, et al. Evaluation of a hexavalent-pentavalent-hexavalent infant primary vaccination series followed by a pentavalent booster vaccine in healthy infants and toddlers. Pediatr Infect Dis J. 2019;38(3):317–22.CrossRefPubMedGoogle Scholar
  8. 8.
    Prymula R, Kieninger D, Feroldi E, et al. Immunogenicity and safety of primary and booster vaccinations of a fully liquid DTaP-IPV-HB-PRP-T hexavalent vaccine in healthy infants and toddlers in Germany and the Czech Republic. Pediatr Infect Dis J. 2018;37(8):823–30.CrossRefPubMedGoogle Scholar
  9. 9.
    Ceyhan M, Yildirim I, Tezer H, et al. A fully liquid DTaP-IPV-HB-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Turkish infants and toddlers. Turk J Med Sci. 2017;47(4):1247–56.CrossRefPubMedGoogle Scholar
  10. 10.
    Lopez P, Arguedas Mohs A, Abdelnour Vasquez A, et al. A randomized controlled study of a fully liquid DTaP-IPV-HB-PRP-T hexavalent vaccine for primary and booster vaccinations of healthy infants and toddlers in Latin America. Pediatr Infect Dis J. 2017;36(11):e272–82.CrossRefPubMedGoogle Scholar
  11. 11.
    Kim YK, Vidor E, Kim HM, et al. Immunogenicity and safety of a fully liquid DTaP-IPV-HB-PRP ~ T hexavalent vaccine compared with the standard of care in infants in the Republic of Korea. Vaccine. 2017;35(32):4022–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Vesikari T, Borrow R, Da Costa X, et al. Concomitant administration of a fully liquid, ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal serogroup C conjugate vaccine in infants. Vaccine. 2017;35(3):452–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Chhatwal J, Lalwani S, Vidor E. Immunogenicity and safety of a liquid hexavalent vaccine in Indian infants. Indian Pediatr. 2017;54(1):15–20.CrossRefPubMedGoogle Scholar
  14. 14.
    Vesikari T, Silfverdal SA, Jordanov E, et al. A randomized, controlled study of DTaP-IPV-HB-PRP-T, a fully liquid hexavalent vaccine, administered in a 3-, 5- and 11- to 12-month schedule. Pediatr Infect Dis J. 2017;36(1):87–93.CrossRefPubMedGoogle Scholar
  15. 15.
    Paterson L. The European medicines agency’s article 58 procedure: reflections on the first approval for a vaccine. Regul Rapporteur. 2013;10(4):19–23.Google Scholar
  16. 16.
    Sanofi Pasteur. Fact sheet: a fully-liquid, ready to use 6-in-1 pediatric vaccine. 2018. https://www.sanofipasteur.com. Accessed 10 Jun 2019.
  17. 17.
    Madhi SA, Mitha I, Cutland C, et al. Immunogenicity and safety of an investigational fully liquid hexavalent combination vaccine versus licensed combination vaccines at 6, 10, and 14 weeks of age in healthy South African infants. Pediatr Infect Dis J. 2011;30(4):e68–74.CrossRefPubMedGoogle Scholar
  18. 18.
    Tregnaghi MW, Zambrano B, Santos-Lima E. Immunogenicity and safety of an investigational hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae B conjugate combined vaccine in healthy 2-, 4-, and 6-month-old Argentinean infants. Pediatr Infect Dis J. 2011;30(6):e88–96.CrossRefPubMedGoogle Scholar
  19. 19.
    Lanata C, Zambrano B, Ecker L, et al. Immunogenicity and safety of a fully liquid DTaP-IPV-Hep B-PRP-T vaccine at 2-4-6 months of age in Peru. J Vaccines Vaccin. 2012.  https://doi.org/10.4172/2157-7560.1000128.CrossRefGoogle Scholar
  20. 20.
    Kosalaraksa P, Thisyakorn U, Benjaponpitak S, et al. Immunogenicity and safety study of a new DTaP-IPV-Hep B-PRP-T combined vaccine compared to a licensed DTaP-IPV-Hep B//PRP-T comparator, both concomitantly administered with a 7-valent pneumococcal conjugate vaccine at 2, 4, and 6 months of age in Thai infants. Int J Infect Dis. 2011;15(4):e249–56.CrossRefPubMedGoogle Scholar
  21. 21.
    Becerra Aquino AG, Gutierrez Brito M, Aranza Doniz CE, et al. A fully liquid DTaP-IPV-Hep B-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Mexican children. Vaccine. 2012;30(45):6492–500.CrossRefGoogle Scholar
  22. 22.
    Macias M, Lanata CF, Zambrano B, et al. Safety and immunogenicity of an investigational fully liquid hexavalent DTaP-IPV-Hep B-PRP-T vaccine at two, four and six months of age compared with licensed vaccines in Latin America. Pediatr Infect Dis J. 2012;31(8):e126–32.CrossRefPubMedGoogle Scholar
  23. 23.
    Madhi SA, Koen A, Cutland C, et al. Antibody persistence and booster vaccination of a fully liquid hexavalent vaccine coadministered with measles/mumps/rubella and varicella vaccines at 15–18 months of age in healthy South African infants. Pediatr Infect Dis J. 2013;32(8):889–97.PubMedGoogle Scholar
  24. 24.
    Kosalaraksa P, Chokephaibulkit K, Benjaponpitak S, et al. Persistence of hepatitis B immune memory until 9–10 years of age following hepatitis B vaccination at birth and DTaP-IPV-HB-PRP ~ T vaccination at 2, 4 and 6 months. Hum Vaccin Immunother. 2018;14(5):1257–65.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Santos-Lima E, B’Chir S, Lane A. Combined immunogenicity data for a new DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim) following primary series administration at 2, 4, 6 months of age in Latin America. Vaccine. 2013;31(9):1255–8.CrossRefPubMedGoogle Scholar
  26. 26.
    European Medicines Agency. Hexyon: assessment report (EMA/373968/2013). 2013. https://www.ema.europa.eu. Accessed 10 Jun 2019.
  27. 27.
    Martinelli D, Fortunato F, Moffa L, et al. Post-marketing surveillance of Hexyon vaccine administered in preterm infants in the apulia region (Italy) in 2017 [abstract no. ESPID19-0212 + poster]. In: 37th Annual Meeting of the European Society for Paediatric Infectious Diseases. 2019.Google Scholar
  28. 28.
    Bozzola E, Spina G, Russo R, et al. Mandatory vaccinations in European countries, undocumented information, false news and the impact on vaccination uptake: the position of the Italian pediatric society. Ital J Pediatr. 2018;44(1):67.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    European Centre for Disease Prevention and Control. Vaccination schedules for individual European countries and specific age groups. 2019. https://ecdc.europa.eu. Accessed 20 May 2019.
  30. 30.
    Syed YY. DTaP5-HB-IPV-Hib vaccine (Vaxelis®): a review of its use in primary and booster vaccination. Pediatr Drugs. 2017;19(1):69–80.CrossRefGoogle Scholar
  31. 31.
    Dhillon S. DTPa-HBV-IPV/Hib Vaccine (Infanrix hexa™): a review of its use as primary and booster vaccination. Drugs. 2010;70(8):1021–58.CrossRefPubMedGoogle Scholar
  32. 32.
    Plotkin SA, Liese J, Madhi SA, et al. A DTaP-IPV//PRP-T vaccine (PentaximTM): a review of 16 years’ clinical experience. Expert Rev Vaccines. 2011;10(7):981–1005.CrossRefPubMedGoogle Scholar
  33. 33.
    Vidor E, Plotkin SA. Immunogenicity of a two-component (PT & FHA) acellular pertussis vaccine in various combinations. Hum Vaccin. 2008;4(5):328–40.CrossRefPubMedGoogle Scholar
  34. 34.
    Tregnaghi MW, Voelker R, Santos-Lima E, et al. Immunogenicity and safety of a novel yeast Hansenula polymorpha-derived recombinant Hepatitis B candidate vaccine in healthy adolescents and adults aged 10-45 years. Vaccine. 2010;28(20):3595–601.CrossRefPubMedGoogle Scholar
  35. 35.
    Lyabis O, Feroldi E, Jordanov E, et al. Long-term hepatitis B immunity after different immunization schedules with Sanofi Pasteur’s hexavalent DTAP-IPV-HB-PRP-T vaccine: a review [abstract no. 19-0890]. In: 37th Annual Meeting of the European Society for Paediatric Infectious Disease (ESPID). 2019.Google Scholar
  36. 36.
    Orsi A, Azzari C, Bozzola E, et al. Hexavalent vaccines: characteristics of available products and practical considerations from a panel of Italian experts. J Prev Med Hyg. 2018;59(2):E107–19.PubMedPubMedCentralGoogle Scholar
  37. 37.
    World Health Organization. Pertussis vaccines: WHO position paper—August 2015. Wkly Epidemiol Rec. 2015;90(35):433–60.Google Scholar
  38. 38.
    Smittskyddsinstitutet. Pertussis surveillance in Sweden: progress report October 1997—September 2006 with an executive summary. 2008. https://www.folkhalsomyndigheten.se. Accessed 10 Jun 2019.
  39. 39.
    Simondon F, Preziosi MP, Yam A, et al. A randomized double-blind trial comparing a two-component acellular to a whole-cell pertussis vaccine in Senegal. Vaccine. 1997;15(15):1606–12.CrossRefPubMedGoogle Scholar
  40. 40.
    Gustafsson L, Hessel L, Storsaeter J, et al. Long-term follow-up of Swedish children vaccinated with acellular pertussis vaccines at 3, 5, and 12 months of age indicates the need for a booster dose at 5 to 7 years of age. Pediatrics. 2006;118(3):978–84.CrossRefPubMedGoogle Scholar
  41. 41.
    Rendi-Wagner P, Kundi M, Mikolasek A, et al. Hospital-based active surveillance of childhood pertussis in Austria from 1996 to 2003: estimates of incidence and vaccine effectiveness of whole-cell and acellular vaccine. Vaccine. 2006;24(33–34):5960–5.CrossRefPubMedGoogle Scholar
  42. 42.
    Chit A, Zivaripiran H, Shin T, et al. Acellular pertussis vaccines effectiveness over time: a systematic review, meta-analysis and modeling study. PLoS One. 2018;13(6):e0197970.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    World Health Organization. Haemophilus influenzae type b (Hib) vaccination position paper—September 2013. Wkly Epidemiol Rec. 2013;88(39):413–28.Google Scholar
  44. 44.
    Morris SK, Moss WJ, Halsey N. Haemophilus influenzae type b conjugate vaccine use and effectiveness. Lancet Infect Dis. 2008;8(7):435–43.CrossRefPubMedGoogle Scholar
  45. 45.
    Georges S, Lepoutre A, Dabernat H, et al. Impact of Haemophilus influenzae type b vaccination on the incidence of invasive Haemophilus influenzae disease in France, 15 years after its introduction. Epidemiol Infect. 2013;141(9):1787–96.CrossRefPubMedGoogle Scholar
  46. 46.
    Kalies H, Grote V, Siedler A. Effectiveness of hexavalent vaccines against invasive Haemophilus influenzae type b disease: Germany’s experience after 5 years of licensure. Vaccine. 2008;26(20):2545–52.CrossRefPubMedGoogle Scholar
  47. 47.
    Lyabis O, Bonanni P, Icardi P, et al. Role of fully liquid ready-to-use vaccine and vaccines that require reconstitution in minimization of vaccination errors: focused literature review [abstract no. 19-0526]. In: 37th Annual Meeting of the European Society for Paediatric Infectious Disease (ESPID). 2019.Google Scholar
  48. 48.
    Bakhache P, Virey B, Bienenfeld C. Knowledge and practices regarding infant vaccination: results of a survey of French physicians. Eur J Pediatr. 2019;178(4):533–40.CrossRefPubMedGoogle Scholar
  49. 49.
    Lloyd AJ, Nafees B, Ziani E, et al. What are the preferences of health care professionals in Germany regarding fully liquid, ready-to-use hexavalent pediatric vaccine versus hexavalent pediatric vaccine that needs reconstitution? Patient Prefer Adherence. 2015;9:1517–24.PubMedPubMedCentralGoogle Scholar
  50. 50.
    De Coster I, Fournie X, Faure C, et al. Assessment of preparation time with fully-liquid versus non-fully liquid paediatric hexavalent vaccines. A time and motion study. Vaccine. 2015;33(32):3976–82.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.SpringerAucklandNew Zealand

Personalised recommendations