Puthanakit T.LI-MIN HUANGChiu 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.2021-06-242021-06-2420160022-1899https://www.scopus.com/inward/record.uri?eid=2-s2.0-84988975003&doi=10.1093%2finfdis%2fjiw036&partnerID=40&md5=99abbb325733e3c2df8452a6ba743244https://scholars.lib.ntu.edu.tw/handle/123456789/566416Background. 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 2016.2-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[SDGs]SDG3[SDGs]SDG5neutralizing 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 Adultjournal article10.1093/infdis/jiw036269087262-s2.0-84988975003