Hernández-Ávila Mauricio, Torres-Ibarra Leticia, Stanley Margaret, Salmerón Jorge, Cruz-Valdez Aurelio, Muñoz Nubia, Herrero Rolando, Villaseñor-Ruíz Ignacio F, Lazcano-Ponce Eduardo
a Center for Population Health Research; National Institute of Public Health ; Cuernavaca , Morelos , Mexico.
b University of Cambridge ; Cambridge , UK.
Hum Vaccin Immunother. 2016;12(1):30-8. doi: 10.1080/21645515.2015.1058458. Epub 2015 Jul 25.
The cost of HPV vaccines and the need for 3 doses remains a barrier for their inclusion in routine vaccination schedules for girls in low and middle income countries. In a non-inferiority study, we aimed to compare the immunogenicity of a standard 3 doses and a 2 doses schedule. We enrolled 450 participants in an open-label non-randomized clinical trial to evaluate the immunogenicity induced at different ages by the licensed HPV6/11/16/18 quadrivalent vaccine in a 2 doses schedule (0-6 months, n = 150 girls aged 9-10 y) and 3 doses schedule (0, 2, and 6 months; n = 150 girls aged 9-10 y and n=150 women aged 18 to 24 years). To assess the antibody response, blood samples were obtained at Month 7 and 21 after the first vaccination from participants in all study groups. cLIA testing was performed at Merck Research Laboratories. Antibody levels were expressed as milli-Merck units (mMU) per ml. Primary outcome was non-inferiority (95% CI, lower bound >0.5) of the geometric mean titers (GMT) ratios for HPV6, HPV11, HPV16 and HPV18 antibodies 7 and 21 months after the first dose among girls receiving 2 doses compared with young women and girls receiving 3 doses. All vaccinees were seropositive for both HPV16 and HPV18 antibodies at month 7. At month 21, 98.5 and 56.6% of women 18-24 y old were seropositive for HPV16 and 18, respectively. For girls in the three doses group, seropositivity rates were 99.3 and 86.3% for HPV16 and 18, respectively. For girls in the two doses group rates were 99.3 and 70.2% for HPV16 and 18, respectively. The two doses schedule was non-inferior compared to the 3 doses schedule in same-age girls and to the group of adult women after 21 months of the first vaccine dose. Our results are in agreement with similar trials evaluating the immune response of a 2 doses schedule of both HPV vaccines, supporting the recent WHO recommendation as well as the Mexican policy to incorporate the 2 doses schedule for girls aged 9-11 y.
人乳头瘤病毒（HPV）疫苗的成本以及需接种3剂次的要求，仍是低收入和中等收入国家将其纳入女孩常规疫苗接种计划的一个障碍。在一项非劣效性研究中，我们旨在比较标准3剂次和2剂次接种方案的免疫原性。我们纳入450名参与者进行一项开放标签非随机临床试验，以评估在2剂次接种方案（0月和6月，n = 150名9至10岁女孩）和3剂次接种方案（0月、2月和6月；n = 150名9至10岁女孩和n = 150名18至24岁女性）下，已获许可的HPV6/11/16/18四价疫苗在不同年龄诱导产生的免疫原性。为评估抗体反应，在首次接种疫苗后的第7个月和第21个月，从所有研究组的参与者中采集血样。在默克研究实验室进行化学发光免疫分析（cLIA）检测。抗体水平以每毫升毫默克单位（mMU）表示。主要结局是在首次接种疫苗7个月和21个月后，接受2剂次接种的女孩与接受3剂次接种的年轻女性和女孩相比，HPV6、HPV11、HPV16和HPV18抗体的几何平均滴度（GMT）比值的非劣效性（95%置信区间，下限>0.5）。所有疫苗接种者在第7个月时HPV16和HPV18抗体均呈血清阳性。在第21个月时，18至24岁女性中分别有98.5%和56.6%的人HPV16和HPV18抗体呈血清阳性。对于3剂次组的女孩，HPV16和HPV18的血清阳性率分别为99.3%和86.3%。对于2剂次组的女孩，HPV16和HPV18的血清阳性率分别为99.3%和70.2%。在首次接种疫苗21个月后，2剂次接种方案与同年龄女孩的3剂次接种方案以及成年女性组相比，具有非劣效性。我们的结果与评估两种HPV疫苗2剂次接种方案免疫反应的类似试验结果一致，支持世界卫生组织（WHO）最近的建议以及墨西哥将2剂次接种方案纳入9至11岁女孩接种计划的政策。
