title: Immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted vaccine administered according to an alternative dosing schedule compared with the standard dosing schedule in healthy women aged 15 to 25 years: results from a randomized study.
abstract: BACKGROUND
  The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine is immunogenic, has a clinically acceptable safety profile, and prevents incident and persistent HPV-16/18 infection and cervical precancerous lesions. This study (NCT00552279) evaluated the vaccine when administered according to an alternative dosing schedule (0-1-12 months) compared with the standard dosing schedule (0-1-6 months).
  
  
  METHODS
  The study was of randomized open design and was conducted at multiple centers in Europe. Healthy women aged 15 to 25 years were randomized (1:1) to receive HPV-16/18 vaccine according to the standard schedule at months 0, 1, and 6 (n = 401) or an alternative schedule at months 0, 1, and 12 (n = 403). HPV-16 and -18 antibodies were measured by enzyme-linked immunosorbent assay at months 0, 2, and 7 or 13 (depending on group); noninferiority evaluation was performed sequentially for seroconversion rates and geometric mean antibody titers. Primary analysis of immunogenicity was based on the according-to-protocol cohort. Vaccine safety and reactogenicity were assessed on the total vaccinated cohort.
  
  
  RESULTS
  Predefined noninferiority criteria were met 1 month after the third vaccine dose when the HPV-16/18 vaccine was administered according to the 0-1-12 month schedule compared with the 0-1-6 month schedule in terms of seroconversion rates for HPV-16 (100% and 100%) and HPV-18 (99.7% and 100%) and geometric mean antibody titers for HPV-16 (11884.7 and 10311.9 ELISA units/mL) and HPV-18 (4501.3 and 3963.6 ELISA units/mL), respectively. The HPV-16/18 vaccine had a clinically acceptable safety profile when administered according to either schedule.
  
  
  CONCLUSIONS
  The third dose of the HPV-16/18 vaccine can be administered any time between 6 and 12 months after the first dose, with adequate immunogenicity and a clinically acceptable safety profile.
authors.affiliation: Department of Maternal and Pediatric Sciences, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy. Susanna.esposito@unimi.it
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
authors.forename: Victoria
authors.initials: V
authors.lastname: Birlutiu
authors.forename: Pavol
authors.initials: P
authors.lastname: Jarcuska
authors.forename: Antonio
authors.initials: A
authors.lastname: Perino
authors.forename: Sorin Claudiu
authors.initials: SC
authors.lastname: Man
authors.forename: Radu
authors.initials: R
authors.lastname: Vladareanu
authors.forename: Dorothée
authors.initials: D
authors.lastname: Meric
authors.forename: Kurt
authors.initials: K
authors.lastname: Dobbelaere
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* / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005060:Europe; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods*; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18