Durable antibody responses following one dose of the bivalent human papillomavirus L1 virus-like particle vaccine in the Costa Rica Vaccine Trial.
Durable antibody responses following one dose of the bivalent human papillomavirus L1 virus-like particle vaccine in the Costa Rica Vaccine Trial.
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DOI：
10.1158/1940-6207.capr-13-0203
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发表时间：
2013-11
期刊：
影响因子：
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通讯作者：
CVT Group
中科院分区：
文献类型：
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作者：
Safaeian M;Porras C;Pan Y;Kreimer A;Schiller JT;Gonzalez P;Lowy DR;Wacholder S;Schiffman M;Rodriguez AC;Herrero R;Kemp T;Shelton G;Quint W;van Doorn LJ;Hildesheim A;Pinto LA;CVT Group
哥斯达黎加HPV 16/18疫苗试验（CVT）显示，在接受一剂、两剂或推荐的三剂二价HPV 16/18 L1病毒样颗粒（VLP）疫苗的妇女中，针对12个月HPV 16/18持续感染的4年疫苗有效性相似。减毒活病毒疫苗，而不是简单亚单位疫苗，通常在单剂量后诱导持久的终身抗体应答。目前还不清楚非感染性VLP疫苗在这方面是否表现得更像活病毒或简单亚单位疫苗。为了探索有效性将持续更长时间的可能性，我们通过在四个接种组中使用招募、接种和四年内每年访视的血清通过VLP-ELISA测量HPV 16和HPV 18特异性抗体来调查该疫苗的抗体的强度和持久性;单次给药（n = 78）、间隔1个月的两次给药（n = 140）、间隔6个月的两次给药（n = 52）和3次计划给药（n = 120，随机选择）。我们还检测了113例HPV 16或HPV 18 L1血清阳性妇女接种前的入组血清，可能来自自然感染。在4年时，所有组中100%的妇女保持HPV 16/18血清阳性;扩展的两剂组中的HPV 16/18几何平均滴度（GMT）不劣于三剂组，ELISA滴度与所有组中的中和滴度高度相关。与自然感染组相比，两剂次接种组HPV 16/18 GMT分别至少高出24和14倍，一剂次接种组分别至少高出9和5倍。单次给药后的抗体水平从第6个月至第48个月保持稳定。结果提高了即使是单剂量HPV VLP也会产生长期保护的可能性。
The Costa Rica HPV16/18 Vaccine Trial (CVT) showed that four-year vaccine efficacy against 12-month HPV16/18 persistent infection was similarly high among women who received one, two, or the recommended three doses of the bivalent HPV16/18 L1 virus-like particle (VLP) vaccine. Live-attenuated viral vaccines, but not simple-subunit vaccines, usually induce durable lifelong antibody responses after a single dose. It is unclear whether noninfectious VLP vaccines behave more like live-virus or simple-subunit vaccines in this regard. To explore the likelihood that efficacy will persist longer term, we investigated the magnitude and durability of antibodies to this vaccine by measuring HPV16- and HPV18-specific antibodies by VLP-ELISA using serum from enrollment, vaccination, and annual visits through four years in four vaccinated groups; one-dose (n = 78), two-doses separated by one month (n = 140), two doses separated by six months (n = 52), and three scheduled doses (n = 120, randomly selected). We also tested enrollment sera from n = 113 HPV16- or HPV18 L1-seropositive women prevaccination, presumably from natural infection. At four years, 100% of women in all groups remained HPV16/18 seropositive; both HPV16/18 geometric mean titers (GMT) among the extended two-dose group were non-inferior to the three-dose group, and ELISA titers were highly correlated with neutralization titers in all groups. Compared with the natural infection group, HPV16/18 GMTs were, respectively, at least 24 and 14 times higher among the two-dose and 9 and 5 times higher among one-dose vaccinees. Antibody levels following one-dose remained stable from month 6 through month 48. Results raise the possibility that even a single dose of HPV VLPs will induce long-term protection.