A ten-year study of immunogenicity and safety of the AS04-HPV-16/18 vaccine in adolescent girls aged 10-14 years
Journal
Human Vaccines and Immunotherapeutics
Journal Volume
15
Journal Issue
7月8日
Pages
1970-1979
Date Issued
2019
Author(s)
Schwarz T.F.
Valencia A.
Panzer F.
Chiu C.-H.
Decreux A.
Poncelet S.
Karkada N.
Folschweiller N.
Lin L.
Dubin G.
Struyf F.
Abstract
This study assessed long-term immunogenicity and safety following 3 doses of AS04-adjuvanted human papillomavirus (HPV)-16/18 L1 virus-like particle (VLP) vaccine in females 10–14 years old. Girls included in the immunogenicity subset in the primary controlled, observer-blinded, randomized study (NCT00196924) who received 3 doses were invited for a 10-year follow-up (NCT00316706 and NCT00877877). Serum antibody responses against HPV-16/18 (vaccine types) and HPV-31/45 (non-vaccine types) were measured by enzyme-linked immunosorbent assay (ELISA) using type-specific VLP as coating antigens. Serious adverse events (SAEs) and pregnancy information were recorded. At Month (M) 120, all subjects (N = 418, according-to-protocol immunogenicity cohort) were seropositive for anti-HPV-16/18 antibodies. Geometric mean titers (GMTs) were 1589.9 ELISA Units [EU]/mL (95% confidence interval [CI]: 1459.8–1731.6) for anti-HPV-16 and 597.2 EU/mL (95% CI: 541.7–658.5) for anti-HPV-18 in subjects seronegative at baseline for the type analyzed. Post hoc mathematical modeling predicted a durability ?50 years for anti-HPV-16 and anti-HPV-18. For the non-vaccine humoral type response, all initially seronegative subjects had seroconverted at M7, with anti-HPV-31 GMT of 2030.5 EU/mL (95% CI: 1766.2–2334.4) and anti-HPV-45 GMT of 2300.8 EU/mL (95% CI: 2036.8–2599.0). At M120, 87.7% and 85.1% remained seropositive for anti-HPV-31 with GMT of 242.9 EU/mL (95% CI: 201.4–293.0) and anti-HPV-45 with GMT of 204.7 EU/mL (95% CI: 170.0–246.6). During the 10-year follow-up, no SAEs or abnormal pregnancy outcomes were causally related to vaccination. Three doses of the AS04-HPV-16/18 vaccine induced high and sustained antibody response against HPV-16,18,31 and 45 in girls aged 10–14 years during the 10-year follow-up, with an acceptable long-term safety profile. ? 2019, ? 2019 GlaxoSmithKline Biologicals SA. Published with license by Taylor & Francis Group, LLC.
Subjects
cross-reactivity; HPV-16/18 AS04-adjuvanted vaccine; HPV-31; HPV-45; immunogenicity persistence; non-vaccine types; predictive modeling; safety
Other Subjects
virus antibody; virus like particle vaccine; Wart virus vaccine; human papillomavirus vaccine, L1 type 16, 18; immunological adjuvant; virus antibody; Wart virus vaccine; adolescent; antibody response; antibody titer; Article; child; clinical trial; clinical trial (topic); cohort analysis; controlled clinical trial; controlled study; drug safety; enzyme linked immunosorbent assay; female; follow up; human; Human papillomavirus type 16; Human papillomavirus type 18; Human papillomavirus type 31; Human papillomavirus type 45; immunogenicity; papillomavirus infection; pregnancy; randomized controlled trial; seroconversion; single blind procedure; vaccination; blood; immunology; multicenter study; papillomavirus infection; phase 3 clinical trial; time factor; uterine cervix tumor; vaccine immunogenicity; Adjuvants, Immunologic; Adolescent; Antibodies, Viral; Child; Female; Follow-Up Studies; Human papillomavirus 16; Human papillomavirus 18; Humans; Immunogenicity, Vaccine; Papillomavirus Infections; Papillomavirus Vaccines; Time Factors; Uterine Cervical Neoplasms; Vaccination
Publisher
Taylor and Francis Inc.
Type
journal article