Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose schedule compared to the licensed 3-dose schedule

Abstract

The immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix®, GlaxoSmithKline Biologicals) administered according to its licensed vaccination schedule (3-dose, 3D) and formulation (20 μg of each HPV antigen; 20/20F) has previously been demonstrated. This partially-blind, controlled, randomized trial (NCT00541970) evaluated 2-dose (2D) schedules using the licensed 20/20F or an alternative formulation containing 40 μg of each antigen (40/40F), compared with the licensed 3D schedule. Healthy females stratified by age (9-14, 15-19, 20-25 y) were randomized to receive 2 doses of 20/20F at Months (M) 0,6 (n=240), 40/40F at M0,6 (n=241) or 40/40F at M0,2 (n=240), or 3 doses of 20/20F at M0,1,6 (licensed schedule/formulation, n=239). One month after the last dose, the 3D schedule was not immunologically superior to 2D schedules except in the 40/40F M0,2 group for HPV-16 (lower limit of 95% CI geometric mean antibody titer (GMT) ratio [2D/3D] < 0.5). For both HPV-16 and HPV-18, the 2D schedules in girls 9-14 y were immunologically non-inferior to the 3D schedule in women 15-25 y (the age group in which efficacy has been demonstrated) (upper limit of 95% CI for GMT ratio [3D/2D] < 2) one month after the last dose. At Month 24, non-inferiority was maintained for the 2D M0,6 schedules in girls 9-14 y versus the 3D schedule in women 15-25 y. All formulations had acceptable reactogenicity and safety profiles. These results indicate that the HPV-16/18 vaccine on a 2D M0,6 schedule is immunogenic and generally well tolerated in girls 9-14 y and that the 2D schedule is likely adequate for younger females.

Comparison of HPV prevalence between HPV-vaccinated and non-vaccinated young adult women (20–26 years)

“…[4][5][6][7][8] These findings demonstrate that even though young girls may have a better immunological response to the HPV vaccine, it is still highly effective when given at older ages. This may be because protection of the vaccine is provided through the production of serum neutralizing anti-HPV IgG antibodies binding to viral particles, [17][18][19] which only requires small amounts of antibody to be present. 20,21 One interesting finding was that vaccinated young adult women had a higher prevalence than unvaccinated women of www.tandfonline.comhigh-risk types other than HPV 16 and 18, and thus are still at risk of cervical cancer and other HPV-related cancers.…”

Human Papilloma Virus. New Opportunities for Vaccination

“…Такая высокая иммуногенность вакцины привела к гипо-тезе о возможной двухдозовой схеме иммунизации для лиц младшей возрастной группы. Эту гипотезу проверяли в двух крупных сравнительных исследованиях иммуно-генности двухдозовой схемы вакцинации девочек в воз-расте 9-14 лет и лицензированной трехдозовой схемы у девушек и женщин 15-25 лет [32,33].…”

Vaccins contre les papillomavirus humains (HPV)

“…Plusieurs études ont exploré la possibilité d'utiliser un tel schéma simplifié. Romanowski et al [18] ont comparé l'immunogénicité du vaccin divalent (contenant un adjuvant lipidique, l'ASO4, adsorbé sur hydroxyde d'aluminium) administré selon un schéma à deux doses chez des jeunes filles âgées de 9 à 14 ans, de 15 à 19 ans et de 20 à 25 ans, à celle du même vaccin administré en trois doses. Un mois après la dernière dose, le schéma à trois doses (0, 1, 6 mois) ne manifeste aucune supé-riorité par rapport au schéma à deux doses (0, 6 mois).…”