Drugs

, Volume 70, Issue 8, pp 1021–1058

DTPa-HBV-IPV/Hib Vaccine (Infanrix hexa™)

A Review of its Use as Primary and Booster Vaccination
Adis Drug Evaluation

Abstract

Infanrix hexa™, administered intramuscularly, is a diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine, indicated for primary and booster vaccination of infants. Infanrix hexa™ should be administered as a two- or three-dose primary vaccination course in infants aged ≤6 months, followed by booster vaccination between 11 and 18 months of age, with an interval of at least 6 months between the last dose of primary vaccination and the booster dose. This article reviews the immunogenicity and protective effectiveness, as well as the reactogenicity and safety of Infanrix hexa™.

Infanrix hexa™ as primary and booster vaccination was safe and highly immunogenic for all its component toxoids/antigens in infants aged <2 years, regardless of vaccination schedules. Its immunogenicity and safety profiles were generally similar to those of currently available vaccines, the diphtheria, tetanus and acellular pertussis-based pentavalent vaccines plus monovalent HBV or Hib vaccines. In large clinical studies, Infanrix hexa™ elicited a strong immune response against vaccine toxoids/antigens, as indicated by high seroprotection/seropositivity/vaccine response rates and geometric mean titres. Moreover, antibodies against vaccine toxoids/antigens persisted for up to a mean of ≈6 years after booster vaccination, and the vaccine induced long-term immune memory against hepatitis B surface antigen and Hib antigen. A strong immune response against Infanrix hexa™ toxoids/antigens after primary vaccination was also induced in infants who had received a dose of HBV vaccine at birth and in pre-term infants, although the response in the latter group was somewhat lower than that in full-term infants. In addition, when coadministered with other childhood vaccines, the immunogenicity of Infanrix hexa™ or that of the concomitantly administered vaccine was generally not altered. Hexavalent vaccines, including Infanrix hexa™, were protective against invasive Hib disease; Infanrix hexa™ is also expected to be protective against pertussis. Most solicited local and general symptoms with Infanrix hexa™ were mild to moderate in intensity and the vaccine was associated with few unsolicited adverse events. Available clinical data from more than 10 years’ experience with the vaccine suggest that Infanrix hexa™ as primary and booster vaccination is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B and invasive Hib disease.

References

  1. 1.
    World Health Organization. Immunization against disease of public health importance: fact sheet no. 288 [online]. Available from URL: http://www.who.int/mediacentre/factsheets/fs288/en/index.html [Accessed 2010 Mar 11]
  2. 2.
    United Nations Children’s Fund. Immunization summary: a statistical reference containing data through 2008 (the 2010 edition) [online]. Available from URL: http://www.childinfo.org/files/Immunization_Summary_2008_r6.pdf [Accessed 2010 Mar 10]
  3. 3.
    Combination vaccines for childhood immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP). Pediatrics 1999 May; 103 (5 Pt 1): 1064–77CrossRefGoogle Scholar
  4. 4.
    Mullany L. Considerations for implementing a new combination vaccine into managed care. Am J Manag Care 2002; 9 (1 Suppl.): S23–9Google Scholar
  5. 5.
    Centers for Disease Control and Prevention. ACIP provisional recommendations for the use of combination vaccines [online]. Available from URL: http://www.cdc.gov/vaccines/recs/provisional/downloads/combo-vax-Aug2009-508.pdf [Accessed 2010 Mar 11]
  6. 6.
    Zepp F, Schmitt HJ, Cleerbout J, et al. Review of 8 years of experience with Infanrix hexa (DTPa-HBV-IPV/Hib hexavalent vaccine). Expert Rev Vaccines 2009 Jun; 8(6): 663–78PubMedCrossRefGoogle Scholar
  7. 7.
    European Medicines Agency. Infanrix hexa: summary of product characteristics [online]. Available from URL: http://www.ema.europa.eu/humandocs/PDFs/EPAR/Infanrixhexa/H-296-PI-en.pdf [Accessed 2010 Apr 18]
  8. 8.
    Tichmann I, Preidel H, Grunert D, et al. Comparison of the immunogenicity and reactogenicity of two commercially available hexavalent vaccines administered as a primary vaccination course at 2, 4 and 6 months of age. Vaccine 2005 May 9; 23(25): 3272–9PubMedCrossRefGoogle Scholar
  9. 9.
    Tichmann I, Grunert D, Habash S, et al. Persistence of antibodies in children primed with two different hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type B vaccines and evaluation of booster vaccination. Hum Vaccin 2006 Nov 31; 2(6): 249–54PubMedCrossRefGoogle Scholar
  10. 10.
    Kilpi TM, Silfverdal SA, Nilsson L, et al. Immunogenicity and reactogenicity of two diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus-Haemophilus influenzae type b vaccines administered at 3, 5 and 11–12 months of age. Hum Vaccin 2009 Jan 28; 5(1): 18–25PubMedCrossRefGoogle Scholar
  11. 11.
    Arístegui J, Dal-Ré R, Díez-Delgado J, et al. Comparison of the reactogenicity and immunogenicity of a combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio (DTPa-HBV-IPV) vaccine, mixed with the Haemophilus influenzae type b (Hib) conjugate vaccine and administered as a single injection, with the DTPa-IPV/Hib and hepatitis B vaccines administered in two simultaneous injections to infants at 2, 4 and 6 months of age. Vaccine 2003 Sep 8; 21(25–26): 3593–600PubMedCrossRefGoogle Scholar
  12. 12.
    European Medicines Agency recommends suspension of Hexavac [media release] 2005 Sep 20 [online]. Available from URL: http://www.ema.europa.eu/humandocs/PDFs/EPAR/Hexavac/29736905en.pdf
  13. 13.
    Zepp F, Knuf M, Heininger U, et al. Safety, reactogenicity and immunogenicity of a combined hexavalent tetanus, diphtheria, acellular pertussis, hepatitis B, inactivated poliovirus vaccine and Haemophilus influenzae type b conjugate vaccine, for primary immunization of infants. Vaccine 2004 Jun 2; 22(17–18): 2226–33PubMedCrossRefGoogle Scholar
  14. 14.
    Avdicová M, Prikazsky V, Hudecková H, et al. Immunogenicity and reactogenicity of a novel hexavalent DTPa-HBV-IPV/Hib vaccine compared to separate concomitant injections of DTPa-IPV/Hib and HBV vaccines, when administered according to a 3, 5 and 11 month vaccination schedule. Eur J Pediatr 2002 Nov; 161(11): 581–7PubMedCrossRefGoogle Scholar
  15. 15.
    Tejedor JC, Omeñaca F, García-Sicilia J, et al. Antibody persistence after primary vaccination with a hexavalent DTPa-HBV-IPV/HiB vaccine coadministered with a meningococcal C-CRM197 vaccine and response to a DTPa-IPV/HiB booster at 18 months of age. Pediatr Infect Dis J 2006 Oct; 25(10): 943–5PubMedCrossRefGoogle Scholar
  16. 16.
    Gabutti G, Zepp F, Schuerman L, et al. Evaluation of the immunogenicity and reactogenicity of a DTPa-HBV-IPV combination vaccine co-administered with a Hib conjugate vaccine either as a single injection of a hexavalent combination or as two separate injections at 3, 5 and 11 months of age. Scand J Infect Dis 2004; 36(8): 585–92PubMedCrossRefGoogle Scholar
  17. 17.
    Omenaca F, Garcia-Sicilia J, Boceta R, et al. Antibody persistence and booster vaccination during the second and fifth years of life in a cohort of children who were born prematurely. Pediatr Infect Dis J 2007 Sep; 26(9): 824–9PubMedCrossRefGoogle Scholar
  18. 18.
    Pichichero ME, Blatter MM, Reisinger KS, et al. Impact of a birth dose of hepatitis B vaccine on the reactogenicity and immunogenicity of diphtheria-tetanus-acellular pertussishepatitis B-inactivated poliovirus-Haemophilus influenzae type b combination vaccination. Pediatr Infect Dis J 2002 Sep; 21(9): 854–9PubMedCrossRefGoogle Scholar
  19. 19.
    Lim FS, Han HH, Jacquet JM, et al. Primary vaccination of infants against hepatitis B can be completed using a combined hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae type B vaccine. Ann Acad Med Singapore 2007 Oct; 36(10): 801–6PubMedGoogle Scholar
  20. 20.
    Zinke M, Kappes R, Kindler K, et al. Immune memory to hepatitis B virus in 4-9-year old children vaccinated in infancy with four doses of hexavalent DTPa-HBV-IPV/Hib vaccine. Hum Vaccin 2009 Sep; 5(9): 592–8PubMedGoogle Scholar
  21. 21.
    Tejedor JC, Moro M, Ruiz-Contreras J, et al. Immunogenicity and reactogenicity of primary immunization with a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzae type B vaccine coadministered with two doses of a meningococcal C-tetanus toxoid conjugate vaccine. Pediatr Infect Dis J 2006 Aug; 25(8): 713–20PubMedCrossRefGoogle Scholar
  22. 22.
    Schmitt HJ, Knuf M, Ortiz E, et al. Primary vaccination of infants with diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio virus and Haemophilus influenzae type b vaccines given as either separate or mixed injections. J Pediatr 2000 Sep; 137(3): 304–12PubMedCrossRefGoogle Scholar
  23. 23.
    Tejedor JC, Omeñaca F, García-Sicilia J, et al. Immunogenicity and reactogenicity of a three-dose primary vaccination course with a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzae type b vaccine coadministered with a meningococcal C conjugate vaccine. Pediatr Infect Dis J 2004 Dec; 23(12): 1109–15PubMedGoogle Scholar
  24. 24.
    Tichmann-Schumann I, Soemantri P, Behre U, et al. Immunogenicity and reactogenicity of four doses of diphtheria-tetanus-three-component acellular pertussis-hepatitis B-inactivated polio virus-Haemophilus influenzae type b vaccine coadministered with 7-valent pneumococcal conjugate vaccine. Pediatr Infect Dis J 2005 Jan; 24(1): 70–7PubMedCrossRefGoogle Scholar
  25. 25.
    Knuf M, Habermehl P, Cimino C, et al. Immunogenicity, reactogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV7) concurrently administered with a DTPa-HBV-IPV/Hib combination vaccine in healthy infants. Vaccine 2006 May 29; 24(22): 4727–36PubMedCrossRefGoogle Scholar
  26. 26.
    Heininger U, Sänger R, Jacquet JM, et al. Booster immunization with a hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus vaccine and Haemophilus influenzae type b conjugate combination vaccine in the second year of life: safety, immunogenicity and persistence of antibody responses. Vaccine 2007 Jan 22; 25(6): 1055–63PubMedCrossRefGoogle Scholar
  27. 27.
    World Health Organization. WHO position paper on Haemophilus influenzae type b conjugate vaccines. Wkly Epidemiol Rec 2006; 81(47): 445–52Google Scholar
  28. 28.
    Zinke M, Disselhoff J, Gartner B, et al. Immunological persistence in 4–6 and 7–9 year olds previously vaccinated in infancy with hexavalent DTPa-HBV-IPV/Hib. Hum Vaccin. Epub 2010 Feb 18; 6 (2)Google Scholar
  29. 29.
    Steiner M, Ramakrishnan G, Gartner B, et al. Lasting immune memory against hepatitis B in children after primary immunization with 4 doses of DTPa-HBV-IPV/Hib in the first and 2nd year of life. BMC Infect Dis 2010; 10: 9PubMedCrossRefGoogle Scholar
  30. 30.
    Giambi C, Bella A, Barale A, et al. A cohort study to evaluate persistence of hepatitis B immunogenicity after administration of hexavalent vaccines. BMC Infect Dis 2008 Jul 28; 8: 100PubMedCrossRefGoogle Scholar
  31. 31.
    Nolan T, Altmann A, Skeljo M, et al. Antibody persistence, PRP-specific immune memory, and booster responses in infants immunised with a combination DTPa-HBV-IPV/Hib vaccine. Vaccine 2004 Nov 15; 23(1): 14–20PubMedCrossRefGoogle Scholar
  32. 32.
    Omeñaca F, Garcia-Sicilia J, García-Corbeira P, et al. Response of preterm newborns to immunization with a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio and Haemophilus influenzae type b vaccine: first experiences and solutions to a serious and sensitive issue. Pediatrics 2005 Dec; 116(6): 1292–8PubMedCrossRefGoogle Scholar
  33. 33.
    Omeñaca F, Garcia-Sicilia J, García-Corbeira P, et al. Antipolyribosyl ribitol phosphate response of premature infants to primary and booster vaccination with a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus/Haemophilus influenzae type b vaccine. Pediatrics 2007 Jan; 119(1): e179–85PubMedCrossRefGoogle Scholar
  34. 34.
    Vazquez L, Garcia F, Ruttimann R, et al. Immunogenicity and reactogenicity of DTPa-HBV-IPV/Hib vaccine as primary and booster vaccination in low-birth-weight premature infants. Acta Paediatr 2008 Sep; 97(9): 1243–9PubMedCrossRefGoogle Scholar
  35. 35.
    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). Pediatr Infect Dis J 2009 Apr; 28 Suppl. 4: S97–S108PubMedGoogle Scholar
  36. 36.
    Zepp F, Behre U, Kindler K, et al. Immunogenicity and safety of a tetravalent measles-mumps-rubella-varicella vaccine co-administered with a booster dose of a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine in healthy children aged 12–23 months. Eur J Pediatr 2007 Aug; 166(8): 857–64PubMedCrossRefGoogle Scholar
  37. 37.
    Vesikari T, Prymula R, Schuster V, et al. Rotarix™ (RIX4414), an oral human rotavirus vaccine, is highly immunogenic when co-administered with diptheria-tetanuspertussis (DTPa)-combined vaccines in healthy infants in Europe. 24th Annual Meeting of the European Society for Paediatric Infectious Diseases; 2006 May 3–5; BaselGoogle Scholar
  38. 38.
    Vesikari T, Karvonen A, Prymula R, et al. Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind controlled study. Lancet 2007 Nov 24; 370(9601): 1757–63PubMedCrossRefGoogle Scholar
  39. 39.
    Esposito S, Tansey A, Thompson A, et al. Safety and immunologic non-inferiority of 13-valent pneumococcal conjugate vacine given as a 3-dose series with routine vaccines in healthy children [abstract no. 258]. 27th Annual Meeting of the European Society for Paediatric Infectious Diseases; 2009 Jun 9–13; BrusselsGoogle Scholar
  40. 40.
    Kieninger DM, Kueper K, Steul K, et al. Safety and immunologic noninferiority of 13-valent pneumococcal conjugate vaccine compared to 7-valent pneumococcal conjugate vaccine given with routine vaccines in healthy infants [abstract no. 111]. 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy/ Infectious Diseases Society of America 46th Annual Meeting; 2008 October 25–28; Washington, DCGoogle Scholar
  41. 41.
    Gimenez-Sanchez F, Kieninger DM, Kueper K, et al. Immunogenicity of Infanrix hexa antigens when given concomitantly with 13-valent pneumococcal conjugate vaccine in healthy infants and toddlers [abstract no. 109]. Infectious Diseases Society of America 47th Annual Meeting; 2009 Oct 29–Nov 1; Philadelphia (PA)Google Scholar
  42. 42.
    Kalies H, Grote V, Siedler A, et al. Effectiveness of hexavalent vaccines against invasive Haemophilus influenzae type b disease: Germany’s experience after 5 years of licensure. Vaccine 2008 May 12; 26(20): 2545–52PubMedCrossRefGoogle Scholar
  43. 43.
    Schmitt HJ, von König CH, Neiss A, et al. Efficacy of acellular pertussis vaccine in early childhood after household exposure. JAMA 1996 Jan 3; 275(1): 37–41PubMedCrossRefGoogle Scholar
  44. 44.
    Greco D, Salmaso S, Mastrantonio P, et al. on behalf of the Progetto Pertosse Working Group. A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis. N Engl J Med 1996 Feb 8; 334(6): 341–8PubMedCrossRefGoogle Scholar
  45. 45.
    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 Sep; 118(3): 978–84PubMedCrossRefGoogle Scholar
  46. 46.
    Saenger R, Maechler G, Potreck M, et al. Booster vaccination with hexavalent DTPa-HBV-IPV/Hib vaccine in the second year of life is as safe as concomitant DTPa-IPV/Hib + HBV administered separately. Vaccine 2005 Jan 19; 23(9): 1135–43PubMedCrossRefGoogle Scholar
  47. 47.
    von Kries R, Toschke AM, Strassburger K, et al. Sudden and unexpected deaths after the administration of hexavalent vaccines (diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, Haemophilius influenzae type b): is there a signal? Eur J Pediatr 2005 Feb; 164(2): 61–9CrossRefGoogle Scholar
  48. 48.
    von Kries R Commenton B. Zinka et al. Unexplained cases of sudden infant death shortly after hexavalent vaccination [letter]. Vaccine 2006 Jul 26; 24(31–32): 5783–4; author reply 5785-6CrossRefGoogle Scholar
  49. 49.
    Chevallier B, Vesikari T, Brzostek J, et al. Safety and reactogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when coadministered with routine childhood vaccines. Pediatr Infect Dis J 2009 Apr; 28 (4 Suppl.): S109–18PubMedCrossRefGoogle Scholar
  50. 50.
    World Health Organization. Hepatitis B [online]. Available from URL: http://www.who.int/csr/disease/hepatitis/HepatitisB_whocdscsrlyo2002_2.pdf [Accessed 2010 Mar 16]
  51. 51.
    World Health Organization. Hepatitis B: fact sheet no. 204 (revised Aug 2008) [online]. Available from URL: http://www.who.int/mediacentre/factsheets/fs204/en/index.html [Accessed 2010 Mar 16]
  52. 52.
    Watt JP, Wolfson LJ, O’Brien KL, et al. Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates. Lancet 2009 Sep 12; 374(9693): 903–11PubMedCrossRefGoogle Scholar
  53. 53.
    EUVAC.NET. National childhood vaccination schedules [online]. Available from URL: http://www.euvac.net/graphics/euvac/vaccination/vaccination.html [Accessed 2010 Mar 12]
  54. 54.
    Kalies H, Grote V, Verstraeten T, et al. The use of combination vaccines has improved timeliness of vaccination in children. Pediatr Infect Dis J 2006 Jun; 25(6): 507–12PubMedCrossRefGoogle Scholar
  55. 55.
    Public Health Agency of Canada. Immunization schedules for infants and children [online]. Available from URL: http://www.phac-aspc.gc.ca/im/is-cv/index-eng.php [Accessed 2010 Mar 12]
  56. 56.
    Eskola J, Ward J, Dagan R, et al. Combined vaccination of Haemophilus influenzae type b conjugate and diphtheriatetanus-pertussis containing acellular pertussis. Lancet 1999 Dec 11; 354(9195): 2063–8PubMedCrossRefGoogle Scholar
  57. 57.
    Pichichero ME. Booster vaccinations: can immunologic memory outpace disease pathogenesis? Pediatrics 2009; 124(6): 1633–41PubMedCrossRefGoogle Scholar
  58. 58.
    Kalies H, Verstraeten T, Grote V, et al. Four and one-half-year follow-up of the effectiveness of diphtheria-tetanus toxoids-acellular pertussis/Haemophilus influenzae type b and diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus/H. influenzae type b combination vaccines in Germany. Pediatr Infect Dis J 2004 Oct; 23(10): 944–50PubMedCrossRefGoogle Scholar
  59. 59.
    Juretzko P, von Kries R, Hermann C. Effectiveness of acellular pertussis vaccine assessed by hospital-based active suveillance in Germany. Clin Infect Dis 2002 Jul; 35(2): 162–7PubMedCrossRefGoogle Scholar
  60. 60.
    World Health Organization. Global Advisory Committee on Vaccine Safety, 2–3 December 2004. Wkly Epidemiol Rec 2005 Jan 7; 80(1): 3–7Google Scholar
  61. 61.
    World Health Organization. Global Advisory Committee on Vaccine Safety, 9–10 June 2005. Wkly Epidemiol Rec 2005 Jul 15; 80(28): 242–7Google Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

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

Personalised recommendations