title: Four-year follow-up of the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine when administered to adolescent girls aged 10-14 years.
abstract: OBJECTIVE
  Long-term immunogenicity and safety of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine when administered to adolescent girls was evaluated.
  
  
  METHODS
  This open-label, follow-up study (NCT00316706) was conducted in 31 centers in Taiwan, Germany, Honduras, Panama, and Colombia. In the initial study (NCT00196924), 1,035 girls aged 10-14 years received the HPV-16/18 AS04-adjuvanted vaccine at 0, 1, and 6 months. Here, geometric mean titers (GMTs) of antibodies against HPV-16, HPV-18, and monophosphoryl lipid A (MPL), a component of the AS04 Adjuvant System, were reported up to month 48.
  
  
  RESULTS
  In the according-to-protocol immunogenicity cohort (N = 563), GMTs at month 48 in initially seronegative participants were 2,374.9 (95% confidence interval: 2,205.7-2,557.0) EL.U/mL for anti-HPV-16 and 864.8 (796.9-938.4) EL.U/mL for anti-HPV-18, that is, six- and threefold higher than the plateau level in a reference study demonstrating vaccine efficacy in young women (age, 15-25 years). All participants remained seropositive for anti-HPV-16 and anti-HPV-18 at month 48. Most participants (81.8%) were seropositive for anti-MPL antibodies before vaccination. Anti-MPL antibody titers in initially seropositive participants increased initially, and then declined. Most initially seronegative participants for anti-MPL seroconverted; 69.6% remained seropositive at month 48, with anti-MPL antibody titers similar to the natural background level. The vaccine was generally well tolerated. No serious adverse events were considered related to vaccination.
  
  
  CONCLUSIONS
  In adolescent girls, the HPV-16/18 AS04-adjuvanted vaccine produces anti-HPV-16 and anti-HPV-18 antibody titers that are maintained for up to 4 years at higher levels than those in young women in whom vaccine efficacy against cervical lesions was demonstrated.
authors.affiliation: Central Laboratory and Vaccination Centre, Stiftung Juliusspital Wuerzburg, Wuerzburg, Germany. t.schwarz@juliusspital.de
authors.forename: Tino F
authors.initials: TF
authors.lastname: Schwarz
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Huang
authors.forename: Doris Maribel Rivera
authors.initials: DM
authors.lastname: Medina
authors.forename: Alejandra
authors.initials: A
authors.lastname: Valencia
authors.forename: Tzou-Yien
authors.initials: TY
authors.lastname: Lin
authors.forename: Ulrich
authors.initials: U
authors.lastname: Behre
authors.forename: Grégory
authors.initials: G
authors.lastname: Catteau
authors.forename: Florence
authors.initials: F
authors.lastname: Thomas
authors.forename: Dominique
authors.initials: D
authors.lastname: Descamps
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000293:Adolescent; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D052162:Human papillomavirus 16 / Q000276:immunology*; D052161:Human papillomavirus 18 / Q000276:immunology*; D006801:Humans; D055261:Immunogenetic Phenomena; D030361:Papillomavirus Infections / Q000517:prevention & control*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control
chemical_list: D000276:Adjuvants, Immunologic; D053918:Papillomavirus Vaccines