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

• 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).

Ämnesord

Medical and Health Sciences  (hsv)

Basic Medicine  (hsv)

Immunology in the medical area  (hsv)

Medicin och hälsovetenskap  (hsv)

Medicinska grundvetenskaper  (hsv)

Immunologi inom det medicinska området  (hsv)

Medical and Health Sciences  (hsv)

Medical Biotechnology  (hsv)

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)  (hsv)

Medicin och hälsovetenskap  (hsv)

Medicinsk bioteknologi  (hsv)

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)  (hsv)

Nyckelord

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)