title: Randomized trial: immunogenicity and safety of coadministered human papillomavirus-16/18 AS04-adjuvanted vaccine and combined hepatitis A and B vaccine in girls.
abstract: OBJECTIVE
  This randomized, open, controlled, multicenter study (110886/NCT00578227) evaluated human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (HPV-16/18 vaccine) coadministered with inactivated hepatitis A and B (HAB) vaccine. Coprimary objectives were to demonstrate noninferiority of hepatitis A, hepatitis B, and HPV-16/18 immune responses at month 7 when vaccines were coadministered, compared with the same vaccines administered alone.
  
  
  METHODS
  Healthy girls (9-15 years) were age-stratified (9, 10-12, and 13-15 years) and randomized to receive HPV (n = 270), HAB (n = 271), or HPV + HAB (n = 272). Vaccines were administered at months 0, 1, and 6. Immunogenicity was evaluated at months 0 and 7.
  
  
  RESULTS
  The hepatitis A immune response was noninferior for HPV + HAB, versus HAB, for seroconversion rates (100% in each group) and geometric mean antibody titers (GMTs) (95% CI) (4,504.2 [3,993.0-5,080.8] and 5,288.4 [4,713.3-5,933.7] mIU/mL, respectively). The hepatitis B immune response was noninferior for HPV + HAB, versus HAB, for anti-HBs seroprotection rates (98.3% and 100%); GMTs were 3,136.5 [2,436.0-4,038.4] and 5,646.5 [4,481.3-7,114.6] mIU/mL, respectively. The HPV-16/18 immune response was noninferior for HPV + HAB, versus HPV, for seroconversion rates (99.6% and 100% for both antigens) and GMTs (22,993.5 [20,093.4-26,312.0] and 26,981.9 [23,909.5-30,449.1] EL.U/mL for HPV-16; 8,671.2 [7,651.7-9,826.6] and 11,182.7 [9,924.8-12,600.1] EL.U/mL for HPV-18, respectively). No subject withdrew because of adverse events. No vaccine-related serious adverse events were reported. Immune responses and reactogenicity were similar in girls aged 9 years compared with the entire study population.
  
  
  CONCLUSIONS
  Results support coadministration of HPV-16/18 vaccine with HAB vaccine in girls aged 9-15 years. The HPV-16/18 vaccine was immunogenic and generally well tolerated in 9-year-old girls.
authors.affiliation: Department of Infectious Diseases Q, Odense University Hospital, Odense, Denmark. courtpedersen@gmail.com
authors.forename: Court
authors.initials: C
authors.lastname: Pedersen
authors.forename: Morten
authors.initials: M
authors.lastname: Breindahl
authors.forename: Naresh
authors.initials: N
authors.lastname: Aggarwal
authors.forename: Johan
authors.initials: J
authors.lastname: Berglund
authors.forename: György
authors.initials: G
authors.lastname: Oroszlán
authors.forename: Sven Arne
authors.initials: SA
authors.lastname: Silfverdal
authors.forename: Péter
authors.initials: P
authors.lastname: Szüts
authors.forename: Michael
authors.initials: M
authors.lastname: O'Mahony
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: David
authors.forename: Kurt
authors.initials: K
authors.lastname: Dobbelaere
authors.forename: Gary
authors.initials: G
authors.lastname: Dubin
authors.forename: Dominique
authors.initials: D
authors.lastname: Descamps
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000536:Aluminum Hydroxide / Q000008:administration & dosage*; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D022362:Hepatitis A Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D052162:Human papillomavirus 16 / Q000187:drug effects / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives*; D030361:Papillomavirus Infections / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D012449:Safety; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control
chemical_list: C532963:ASO4 mixture; D000276:Adjuvants, Immunologic; D022362:Hepatitis A Vaccines; D017325:Hepatitis B Vaccines; D008050:Lipid A; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18; D000536:Aluminum Hydroxide