Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine administered according to 2-and 3-dose schedules in girls aged 9-14 years: Results to month 12 from a randomized trial
2015 (English)In: Human Vaccines & Immunotherapeutics, ISSN 2164-5515, Vol. 11, no 7, 1689-1702 p.Article in journal (Refereed) Published
This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of 2 doses of the HPV-16/18 AS04-adjuvanted vaccine (HPV-16/18(2D)) vs. 2 or 3 doses of the HPV-6/11/16/18 vaccine (HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D)) in healthy girls aged 9-14 y. Girls were randomized (1:1:1) to receive HPV-16/18(2D) at months (M) 0,6 (N = 359), HPV-6/11/16/18(2D) at M0,6 (N = 358) or HPV-6/11/16/18(3D) at M0,2,6 (N = 358). The primary objective was non-inferiority/superiority of HPV-16/18 antibodies by ELISA for HPV-16/18(2D) vs. HPV-6/11/16/18(2D) at M7 in the according-to-protocol immunogenicity cohort (ATP-I) and total vaccinated cohort, respectively. Secondary objectives included non-inferiority/superiority of HPV-16/18(2D) vs. HPV-6/11/16/18(3D) at M7, non-inferiority/superiority at M12, HPV-16/18 neutralizing antibodies, frequencies of T-cells/B-cells, reactogenicity and safety. Antibody responses at M7 for HPV-16/18(2D) were superior to those for HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D) (lower limit of 95% confidence interval for geometric mean titer ratio (GMR) was >1): HPV-16/18(2D)/HPV-6/11/16/18(2D) GMRs were 1.69 [1.49-1.91] for anti-HPV-16 and 4.52 [3.97-5.13] for anti-HPV-18; HPV-16/18(2D)/HPV-6/11/16/18(3D) GMRs were 1.72 [1.54-1.93] for anti-HPV-16 and 3.22 [2.82-3.68] for anti-HPV-18; p = 0.0001 for all comparisons. Non-inferiority/superiority was also demonstrated at M12. Among initially seronegative girls in the ATP-I, neutralizing antibody titers were at least 1.8-fold higher for HPV-16/18(2D) vs. HPV-6/11/16/18(2D) and HPV-6/11/16/18(3D) at M7 and M12. Frequencies of HPV-16/18-specific T-cells and B-cells were in similar ranges between groups. Reactogenicity and safety were in line with the known profile of each vaccine. In conclusion, superior HPV-16/18 antibody responses were elicited by 2 doses of the HPV-16/18 AS04-adjuvanted vaccine compared with 2 or 3 doses of the HPV-6/11/16/18 vaccine in girls (9-14years).
Place, publisher, year, edition, pages
2015. Vol. 11, no 7, 1689-1702 p.
administration schedule, female adolescents, immunogenicity, human papillomavirus (HPV) vaccines, safety, 2D, 2-dose, 3D, 3-dose, AAHS, aluminum hydroxyphosphate sulfate, ANOVA, analysis of variance, AS04, Adjuvant System containing 50 mu g 3-O-desacyl-4-monophosphoryl lipid A (MPL) adsorbed on aluminum salt (500 mu g Al3+), ATP-I, according-to-protocol immunogenicity cohort, CI, confidence interval, CMI, cell-mediated immunity, ED50, effective dose producing 50% response, ELISA, enzyme-linked immunosorbent assay, ELISPOT, enzyme-linked immunosorbent spot assay, EU, ELISA unit, GMR, geometric mean titer ratio, GMT, geometric mean antibody titer, HPV, human papillomavirus, HPV-16, 18(2D), 2-dose schedule of the HPV-16, 18 vaccine, HPV-6, 11, 16, 2-dose schedule of the HPV-6, 18(3D), 3-dose schedule of the HPV-6, IFN, interferon, M, month(s), IgG, immunoglobulin G, PBMC, peripheral blood mononuclear cells, PBNA, pseudovirion-based neutralisation assay, pIMD, potential immune-mediated disease, SAE, serious adverse event, TVC, total vaccinated cohort, VLP, virus-like particle, y, year(s)
Immunology in the medical area Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
IdentifiersURN: urn:nbn:se:uu:diva-259658DOI: 10.1080/21645515.2015.1050570ISI: 000357412800028PubMedID: 26062002OAI: oai:DiVA.org:uu-259658DiVA: diva2:847496
Funding: GlaxoSmithKline Biologicals SA2015-08-202015-08-102015-08-20Bibliographically approved