Virus Reference Department, Public Health England, London, UK.
Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
Vaccine. 2019 Apr 24;37(18):2455-2462. doi: 10.1016/j.vaccine.2019.03.052. Epub 2019 Mar 27.
Bivalent (Cervarix®) and quadrivalent (Gardasil®) Human Papillomavirus (HPV) vaccines demonstrate remarkable efficacy against the targeted genotypes, HPV16 and HPV18, but also a degree of cross-protection against non-vaccine incorporated genotypes, HPV31 and HPV45. These outcomes seem to be supported by observations that the HPV vaccines induce high titer neutralizing antibodies against vaccine types and lower responses against non-vaccine types. Few data are available on the robustness of the immune response against non-vaccine types. We examined the durability of vaccine and non-vaccine antibody responses in a follow up of a head-to-head study of 12-15 year old girls initially randomized to receive three doses of Cervarix® or Gardasil® vaccine. Neutralizing antibodies against both vaccine and non-vaccine types remained detectable up to 7 years following initial vaccination and a mixed effects model was used to predict the decline in antibody titers over a 15 year period. The decline in vaccine and non-vaccine type neutralizing antibody titers over the study period was estimated to be 30% every 5-7 years, with Cervarix® antibody titers expected to remain 3-4 fold higher than Gardasil® antibody titers over the long term. The antibody decline rates in those with an initial response to non-vaccine types were similar to that of vaccine types and are predicted to remain detectable for many years. Empirical data on the breadth, magnitude, specificity and durability of the immune response elicited by the HPV vaccines contribute to improving the evidence base supporting this important public health intervention. Original trial: ClinicalTrials.gov NCT00956553.
二价(Cervarix®)和四价(Gardasil®)人乳头瘤病毒(HPV)疫苗对目标基因型 HPV16 和 HPV18 显示出显著的疗效,但也对非疫苗包含的基因型 HPV31 和 HPV45 具有一定程度的交叉保护作用。这些结果似乎得到了这样的观察结果的支持,即 HPV 疫苗可诱导针对疫苗型的高滴度中和抗体,而对非疫苗型的反应较低。关于针对非疫苗型的免疫反应的稳健性,可用的数据很少。我们在一项头对头研究的随访中检查了针对非疫苗型的抗体反应的持久性,该研究最初将 12-15 岁的女孩随机分配接受三剂 Cervarix®或 Gardasil®疫苗。在初始接种后长达 7 年,仍可检测到针对疫苗和非疫苗型的中和抗体,并且使用混合效应模型来预测 15 年内抗体滴度的下降。在研究期间,疫苗和非疫苗型中和抗体滴度的下降估计为每 5-7 年 30%,预计 Cervarix®抗体滴度在长期内将比 Gardasil®抗体滴度高 3-4 倍。对非疫苗型有初始反应的人的抗体下降率与疫苗型相似,预计在未来多年仍可检测到。HPV 疫苗引起的免疫反应的广度、幅度、特异性和持久性的经验数据有助于提高支持这一重要公共卫生干预措施的证据基础。原始试验:ClinicalTrials.gov NCT00956553。