Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), P.O Box 1, 3720 BA, Bilthoven, The Netherlands; Department of Pathology, VU University Medical Centre (VUmc), P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), P.O Box 1, 3720 BA, Bilthoven, The Netherlands.
J Infect. 2015 Jul;71(1):61-73. doi: 10.1016/j.jinf.2015.02.005. Epub 2015 Feb 21.
The European Medicines Agency (EMA) recently approved two-dose immunization schedules for bivalent (HPV 16/18) and quadrivalent (HPV 6/11/16/18) human papillomavirus (HPV) vaccines in nine to fourteen and thirteen year-old-girls, respectively. Registration was based on trials comparing immunogenicity of two-dose schedules in girls 9-14 years to three-dose schedules in young women 15-26 years. We evaluate comparability of antibody levels between and within age groups and discuss potential implications for monitoring the effectiveness of HPV vaccination.
A systematic literature search was performed for studies comparing immunogenicity of two- to three-dose schedules of HPV vaccination. We compared geometric mean concentrations (GMCs) of vaccine-type antibodies between different dosing schedules across different age groups. Meta-analysis was used to estimate pooled GMC ratios (bivalent vaccine) of two- compared with three-dose schedules within girls.
For both vaccines, two-dose immunization of girls yielded non-inferior GMCs relative to a three-dose schedule in young women up to respectively 36 and 48 months follow-up. Pooled GMC ratios for the bivalent vaccine within girls showed the two-dose schedule becoming inferior to the three-dose schedule in girls for HPV 16 at approximately two years after the first dose. For the quadrivalent vaccine, antibody responses for HPV-18 became inferior from 18 months follow-up onwards when comparing the two-dose schedule with the three-dose schedule within girls.
Two-dose immunization of girls has non-inferior immunogenicity compared to a three-dose schedule among young women. However, non-inferior immunogenicity of two- compared with three-dose schedules within girls has not been shown at all time points. Due to this inconclusive evidence, implementation of two-dose HPV vaccination needs to be monitored closely.
欧洲药品管理局（EMA）最近批准了双价（HPV 16/18）和四价（HPV 6/11/16/18）人乳头瘤病毒（HPV）疫苗在 9 至 14 岁和 13 岁女孩中的两剂免疫接种方案。注册是基于比较 9-14 岁女孩两剂方案和 15-26 岁年轻女性三剂方案免疫原性的试验。我们评估了不同年龄组之间和组内抗体水平的可比性，并讨论了监测 HPV 疫苗有效性的潜在影响。
系统检索了比较 HPV 疫苗两剂和三剂免疫接种方案免疫原性的研究。我们比较了不同年龄组不同剂量方案之间疫苗型抗体的几何平均浓度（GMC）。使用荟萃分析估计了两剂与三剂方案在女孩中的 bivalent 疫苗的 GMC 比值（比）。
对于两种疫苗，在分别随访 36 和 48 个月时，女孩的两剂免疫接种产生了与年轻女性三剂方案相当的非劣效 GMC。在女孩中，两剂与三剂方案的 bivalent 疫苗的 GMC 比值显示，在第一剂后约两年，两剂方案对 HPV 16 的效果劣于三剂方案。对于四价疫苗，从 18 个月随访开始，两剂方案与三剂方案在女孩中相比，HPV-18 的抗体反应变得劣于三剂方案。
与年轻女性的三剂方案相比，女孩的两剂免疫接种具有非劣效的免疫原性。然而，在所有时间点，两剂方案与三剂方案在女孩中的非劣效性免疫原性尚未得到证实。由于证据不明确，需要密切监测两剂 HPV 疫苗的实施。
