Immunogenicity of the 9-Valent HPV Vaccine Using 2-Dose Regimens in Girls and Boys vs a 3-Dose Regimen in Women
Immunogenicity of the 9-Valent HPV Vaccine Using 2-Dose Regimens in Girls and Boys vs a 3-Dose Regimen in Women
复制标题
DOI：
10.1001/jama.2016.17615
复制
发表时间：
2016-12-13
影响因子：
120.7
通讯作者：
Luxembourg, Alain
中科院分区：
文献类型：
--
作者：
Iversen, Ole-Erik;Miranda, Maria Jose;Luxembourg, Alain
人类乳头瘤病毒（HPV）感染会导致肛门生殖器癌和疣。9价人乳头瘤病毒疫苗可预防导致90%宫颈癌的7种高危型人乳头瘤病毒，以及导致90%生殖器疣的2种其他型人乳头瘤病毒。目的：确定9- 14岁的女孩和男孩在接种2剂9价HPV疫苗后，与16 - 26岁的青春期女孩和年轻女性接种3剂HPV疫苗相比，HPV类型特异性抗体反应是否不差。设计、环境和参与者：开放标签、非劣效性、免疫原性试验在15个国家的52个门诊医疗点进行。本研究于2013年12月16日启动，最后一次访问本报告的参与者为2015年6月19日。纳入了5个队列：(1)9至14岁的女孩，间隔6个月接受2剂（n = 301）；(2) 9至14岁的男孩间隔6个月接种2剂（n = 301）；(3) 9至14岁的女孩和男孩间隔12个月接种2剂（n = 301）；(4) 9至14岁的女孩在6个月内接种3剂（n = 301）；(5)对照组为16至26岁的少女和年轻女性，在6个月内接受3次剂量（n = 314）。干预措施：间隔6或12个月接种两剂9价HPV疫苗，或在6个月内接种3剂。主要结局和措施主要终点预先指定为在最后一次剂量后1个月使用竞争性免疫分析法评估针对每种HPV类型的抗体反应。在青春期女孩和年轻女性中，使用抗体几何平均滴度比的非劣效边际为0.67，将三种2剂量方案中的每一种方案与标准3剂量方案进行比较。结果在1518名参与者中（753名女孩[平均年龄，11.4岁]，451名男孩[平均年龄，11.5岁]，314名青春期女孩和年轻女性[平均年龄，21.0岁]），1474人完成了研究，1377人的数据被分析。在最后一次注射后4周，注射2剂的女孩和男孩的HPV抗体反应不低于注射3剂的青春期女孩和年轻女性的HPV抗体反应(P
IMPORTANCE Human papillomavirus (HPV) infections cause anogenital cancers and warts. The 9-valent HPV vaccine provides protection against 7 high-risk types of HPV responsible for 90% of cervical cancers and 2 other HPV types accounting for 90% of genital warts.OBJECTIVE To determine whether HPV type-specific antibody responses would be noninferior among girls and boys aged 9 to 14 years after receiving 2 doses of the 9-valent HPV vaccine compared with adolescent girls and young women aged 16 to 26 years receiving 3 doses.DESIGN, SETTING, AND PARTICIPANTS Open-label, noninferiority, immunogenicity trial conducted at 52 ambulatory care sites in 15 countries. The study was initiated on December 16, 2013, with the last participant visit for this report on June 19, 2015. Five cohorts were enrolled: (1) girls aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (2) boys aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (3) girls and boys aged 9 to 14 years to receive 2 doses 12 months apart (n = 301); (4) girls aged 9 to 14 years to receive 3 doses over 6 months (n = 301); and (5) a control group of adolescent girls and young women aged 16 to 26 years to receive 3 doses over 6 months (n = 314).INTERVENTIONS Two doses of the 9-valent HPV vaccine administered 6 or 12 months apart or 3 doses administered over 6 months.MAIN OUTCOMES AND MEASURES The primary end point was prespecified as the antibody response against each HPV type assessed 1 month after the last dose using a competitive immunoassay. Each of the three 2-dose regimens was compared with the standard 3-dose schedule in adolescent girls and young women using a noninferiority margin of 0.67 for the ratio of the antibody geometric mean titers.RESULTS Of the 1518 participants (753 girls [mean age, 11.4 years]; 451 boys [mean age, 11.5 years]; and 314 adolescent girls and young women [mean age, 21.0 years]), 1474 completed the study and data from 1377 were analyzed. At 4 weeks after the last dose, HPV antibody responses in girls and boys given 2 doses were noninferior to HPV antibody responses in adolescent girls and young women given 3 doses (P