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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

Esposito, Susanna MD*; Birlutiu, Victoria MD†; Jarcuska, Pavol PhD‡; Perino, Antonio MD§; Man, Sorin Claudiu PhD¶; Vladareanu, Radu PhD∥; Meric, Dorothée MSc**; Dobbelaere, Kurt MD**; Thomas, Florence DTM**; Descamps, Dominique MD**

Pediatric Infectious Disease Journal: March 2011 - Volume 30 - Issue 3 - pp e49-e55
doi: 10.1097/INF.0b013e318206c26e
Online-Only: Original Studies

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.

From the *Department of Maternal and Pediatric Sciences, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy; †Department of Infectious Diseases, “Victor Papilian” Faculty of Medicine, Emergency Clinic Hospital, Sibiu, Romania; ‡Faculty of Medicine, P.J. Safarik University, Kosice, Slovakia; §Dipartimento Materno Infantile, University of Palermo, Palermo, Italy; ¶Pediatrics Department, “Iuliu Hatţieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; ∥Obstetrics and Gynecology Department, Elias University Hospital, Carol Davilla University of Medicine, Bucharest, Romania; and **GlaxoSmithKline Biologicals, Wavre, Belgium.

Accepted for publication November 15, 2010.

Cervarix is a registered trademark of the GlaxoSmithKline group of companies. Supported by GlaxoSmithKline Biologicals.

Writing assistance for this manuscript was provided by Julie Taylor, Peak Biomedical Ltd, Macclesfield, Cheshire, United Kingdom, on behalf of GlaxoSmithKline Biologicals. Editorial assistance and manuscript coordination were provided by Denis Sohy and Jean-Michel Heine, GlaxoSmithKline Biologicals, Wavre, Belgium.

Address for correspondence: Susanna Esposito, MD, Department of Maternal and Pediatric Sciences, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 9, 20122 Milano, Italy. E-mail: Susanna.esposito@unimi.it.

© 2011 Lippincott Williams & Wilkins, Inc.