Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine Follow-up from months 12-24 in a Phase III randomized study of healthy women aged 18-45 years
Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine Follow-up from months 12-24 in a Phase III randomized study of healthy women aged 18-45 years
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DOI：
10.4161/hv.7.12.18281
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发表时间：
2011-12-01
期刊：
影响因子：
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通讯作者：
Dubin, Gary
中科院分区：
文献类型：
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作者：
Einstein, Mark H.;Baron, Mira;Dubin, Gary
在这项观察者盲目研究(NCT00423046)中，按年龄(18-26岁、27-35岁、36-45岁)分层的妇女(N=1,106)被随机(1：1)接种HPV-16/18疫苗(Cervarx(R)，葛兰素史克生物制剂，0、1、6个月)或HPV-6/11/16/18疫苗(Gardasil(R)Merck and Co.，Inc.，0、2、6个月)。第7个月的结果以前是报告的；现在我们报告第24个月的结果。在按方案进行的免疫原性队列(分析的HPV类型的血清阴性和DNA阴性)中，中和抗体(NABS)的血清阳性率在所有年龄段的HPV-16和HPV-6/11/16/18疫苗分别为100%(HPV-16/18疫苗)和97.5-100%(HPV-6/11/16/18疫苗)，而对于HPV-18(HPV-16/18疫苗)和72.3-84.4%(HPV-6/11/16/18疫苗)。与HPV-6/11/16/18疫苗相比，HPV-16疫苗的相应几何平均滴度(GMT)高2.4-5.8倍，HPV-18疫苗的几何平均滴度(GMT)高7.7-9.4倍；在整个接种队列中，HPV-16和HPV-18GMT显著高于HPV-6/11/16/18疫苗(p<；0.0001)。酶联免疫吸附试验(ELISA法)也得到了类似的结果。不同疫苗间宫颈阴道分泌物中抗原特异性抗体的阳性率和GMT无显著差异。在24个月时，接种HPV-16/18疫苗的HPV-16和HPV-18的CD4(+)T细胞应答较高；接种HPV-16/18疫苗的HPV-18的记忆B细胞应答较高，两种HPV-16疫苗的应答相似。两种疫苗的耐受性一般都很好。虽然尚未确定保护的免疫学相关性，但疫苗之间免疫反应大小的差异可能代表保护持续时间的决定因素。
In this observer-blind study (NCT00423046), women (N = 1,106), stratified by age (18-26, 27-35, 36-45 y), were randomized (1: 1) to receive the HPV-16/18 vaccine (Cervarix (R), GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil (R) Merck and Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5-100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0-100% (HPV-16/18 vaccine) and 72.3-84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4-5.8-fold higher for HPV-16 and 7.7-9.4-fold higher for HPV-18 with the HPV-16/18 vaccine vs. the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p < 0.0001) in the total vaccinated cohort (received >= 1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA) were not significantly different between vaccines. At Month 24, CD4(+) T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection.