title: Combined hepatitis A and B vaccines: a review of their immunogenicity and tolerability.
abstract: Three combined hepatitis A and B vaccine preparations are commercially available in various countries: a two-dose paediatric formulation (Ambirix) [administered at months 0 and 6-12]; and a three-dose adult (Twinrix Adult) or paediatric (Twinrix Paediatric) formulation (administered at months 0, 1 and 6). The adult vaccine provides consistent, marked immunogenicity which is at least similar to that of its constituent vaccines used together and with a tolerability profile that is possibly improved. An accelerated, day-0, -7 and -21 regimen has also shown immunogenicity similar to that of the monovalent vaccines given concurrently, and now has an emerging role in adults likely to travel to hepatitis A virus (HAV) and/or hepatitis B virus (HBV) endemic regions within 1 month. The adult vaccine appears effective and generally well tolerated when given concurrently with monovalent typhoid vaccine (Typherix). Immunogenicity of the two-dose paediatric vaccine is high and appears to be similar whether administered as a month-0, -6 or month-0, -12 schedule and when compared to that of the three-dose paediatric vaccine (months 0, 1, 6), both of which provide a similar degree of protection to the adult vaccine. Although both preparations also provide high end-of-schedule seroprotection against hepatitis B surface antigen, protection between the first and second doses of the two-dose regimen appears lower than with the three-dose schedule. Therefore, the three-dose paediatric vaccine is a practical option in individuals at risk of immediate exposure to HBV, while the two-dose regimen may have an important function in immunisation programmes in regions where such risk is low. Combined hepatitis A and B vaccines are generally well tolerated. The most frequently reported adverse events in clinical trials were injection-site pain and redness, and general fatigue and headache; most events were mild and transient. Pharmacoeconomic models suggest the combined vaccine is cost effective compared with no vaccine (in children/adolescents) or monovalent hepatitis B vaccine (in children/adolescents and prison inmates).
  
  
  CONCLUSIONS
  The three commercially available combined hepatitis A and B adult and paediatric vaccines are highly immunogenic and generally well tolerated; the adult vaccine demonstrates immunogenicity at least as marked as that of monovalent hepatitis A and B vaccines. While further research is required to confirm potential advantages such as improved cost effectiveness, the combined vaccines have established a key role in the prevention of hepatitis A and B in defined risk groups, and have an expanding role in population-based vaccination programmes with younger age groups.
authors.affiliation: Adis International Limited, Auckland, New Zealand.
authors.forename: David L
authors.initials: DL
authors.lastname: Murdoch
authors.forename: Karen
authors.initials: K
authors.lastname: Goa
authors.forename: David P
authors.initials: DP
authors.lastname: Figgitt
mesh_terms: D000367:Age Factors; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D022362:Hepatitis A Vaccines / Q000009:adverse effects* / Q000191:economics / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000009:adverse effects* / Q000191:economics / Q000276:immunology*; D006801:Humans; D017778:Vaccines, Combined
chemical_list: D022362:Hepatitis A Vaccines; D017325:Hepatitis B Vaccines; D017778:Vaccines, Combined