Randomized open trial comparing 2-dose regimens of the human papillomavirus 16/18 as04-adjuvanted vaccine in girls aged 9-14 years versus a 3-dose regimen in women aged 15-25 years
Journal
Journal of Infectious Diseases
Journal Volume
214
Journal Issue
4
Pages
525-536
Date Issued
2016
Author(s)
Puthanakit T.
Chiu C.-H.
Tang R.-B.
Schwarz T.F.
Esposito S.
Frenette L.
Giaquinto C.
McNeil S.
Rheault P.
Durando P.
Horn M.
Klar M.
Poncelet S.
De Simoni S.
Friel D.
De Muynck B.
Suryakiran P.V.
Hezareh M.
Descamps D.
Thomas F.
Struyf F.
Abstract
Background. This randomized, open trial compared regimens including 2 doses (2D) of human papillomavirus (HPV) 16/18 AS04-adjuvanted vaccine in girls aged 9-14 years with one including 3 doses (3D) in women aged 15-25 years. Methods. Girls aged 9-14 years were randomized to receive 2D at months 0 and 6 (M0,6; (n = 550) or months 0 and 12 (M0,12; n = 415), and women aged 15-25 years received 3D at months 0, 1, and 6 (n = 482). End points included noninferiority of HPV-16/ 18 antibodies by enzyme-linked immunosorbent assay for 2D (M0,6) versus 3D (primary), 2D (M0,12) versus 3D, and 2D (M0,6) versus 2D (M0,12); neutralizing antibodies; cell-mediated immunity; reactogenicity; and safety. Limits of noninferiority were predefined as <5% difference in seroconversion rate and <2-fold difference in geometric mean antibody titer ratio. Results. One month after the last dose, both 2D regimens in girls aged 9-14 years were noninferior to 3D in women aged 15-25 years and 2D (M0,12) was noninferior to 2D (M0,6). Geometric mean antibody titer ratios (3D/2D) for HPV-16 and HPV-18 were 1.09 (95% confidence interval, .97-1.22) and 0.85 (.76-.95) for 2D (M0,6) versus 3D and 0.89 (.79-1.01) and 0.75 (.67-.85) for 2D (M0,12) versus 3D. The safety profile was clinically acceptable in all groups. Conclusions. The 2D regimens for the HPV-16/18 AS04-adjuvanted vaccine in girls aged 9-14 years (M0,6 or M0,12) elicited HPV-16/18 immune responses that were noninferior to 3D in women aged 15-25 years. ? The Author 2016.
Subjects
2-dose schedule; Adjuvant System containing 50 ?g 3-O-desacyl-4?-monophosphoryl lipid A (MPL) adsorbed on aluminum salt (500 ?g Al3+); AS04; Cell-mediated immunity; Cervical cancer; CMI; Geometric mean antibody titer; GMT; HPV; Human papillomavirus; IgG; Immunogenicity
Other Subjects
neutralizing antibody; Wart virus vaccine; aluminum hydroxide; ASO4 mixture; immunological adjuvant; lipid A; neutralizing antibody; virus antibody; Wart virus vaccine; adolescent; adult; antibody titer; Article; B lymphocyte; CD4+ T lymphocyte; cellular immunity; child; controlled study; cross reaction; dosage schedule comparison; drug dose regimen; drug safety; enzyme linked immunosorbent assay; fatigue; female; fever; headache; human; Human papillomavirus type 16; Human papillomavirus type 18; Human papillomavirus type 31; Human papillomavirus type 45; immune response; immunogenicity; injection site pain; memory cell; myalgia; nerve paralysis; normal human; open study; phase 3 clinical trial; priority journal; randomized controlled trial; reactogenicity; seroconversion; swelling; urticaria; vaccination; age; analogs and derivatives; blood; comparative study; immunization; immunology; Papillomavirus Infections; treatment outcome; young adult; Adjuvants, Immunologic; Adolescent; Age Factors; Aluminum Hydroxide; Antibodies, Neutralizing; Antibodies, Viral; Child; Female; Human papillomavirus 16; Human papillomavirus 18; Humans; Immunization Schedule; Lipid A; Papillomavirus Infections; Papillomavirus Vaccines; Treatment Outcome; Young Adult
Publisher
Oxford University Press
Type
journal article