Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose of HPV vaccine in historical cohorts: an immunobridging analysis of a randomised controlled trial.
Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose of HPV vaccine in historical cohorts: an immunobridging analysis of a randomised controlled trial.
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DOI：
10.1016/s2214-109x(22)00306-0
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发表时间：
2022-10
影响因子：
34.3
通讯作者：
Watson-Jones, Deborah
中科院分区：
文献类型：
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作者：
Baisley, Kathy;Kemp, Troy J.;Kreimer, Aimee R.;Basu, Partha;Changalucha, John;Hildesheim, Allan;Porras, Carolina;Whitworth, Hilary;Herrero, Rolando;Lacey, Charles J.;Schiller, John T.;Lucas, Eric;Mutani, Paul;Dillner, Joakim;Indangasi, Jackton;Muwonge, Richard;Hayes, Richard J.;Pinto, Ligia A.;Watson-Jones, Deborah
人乳头瘤病毒（HPV）疫苗在9-14岁的儿童中以两剂方案给予，或在老年人中以三剂方案给予。我们比较了剂量减少免疫和安全性研究（DoRIS）中一剂HPV疫苗后的抗体应答，这是一项在坦桑尼亚进行的不同HPV疫苗接种时间表的随机试验，与两项观察性HPV疫苗试验（哥斯达黎加疫苗试验[CVT]和印度癌症研究机构[IARC]试验）的抗体应答，这些试验发现一剂疫苗对HPV 16和HPV 18的有效性高达11年。在这项开放标签随机对照试验的免疫桥接分析中，从坦桑尼亚姆万扎的54所政府学校招募女孩参加DoRIS试验。如果女孩年龄在9-14岁之间，身体健康，艾滋病毒呈阴性，就有资格参加。使用12、18和24的排列区组大小，将参与者随机分配（1：1：1：1：1：1）至1、2或3剂2价疫苗（Cervarix，GSK Biologicals，里克森萨尔，比利时）或9价疫苗（Gardasil 9，赛诺菲巴斯德MSD，里昂，法国）。对于该免疫桥接分析，主要目的是比较符合方案人群与历史队列中单次给药后24个月时的几何平均浓度（GMC）：将DoRIS中的一剂2价疫苗组与CVT的2价疫苗Cervarix接种者进行比较，将DoRIS中的一剂9价疫苗组与4价疫苗Gardasil接种者进行比较（Merck Sharp & Dohme，怀特豪斯站，新泽西州，美国）。用病毒样颗粒ELISA检测样本中的HPV 16和HPV 18 IgG抗体。GMC比值（DoRIS试验vs历史队列）的非劣效性预先定义为95% CI的下限大于0.50。本研究注册于ClinicalTrials.gov，NCT 02834637。在2017年2月23日至2018年1月6日期间，我们筛选了1002名女孩的资格，其中930人参加了DoRIS，155人分别被分配到一剂，两剂或三剂2价疫苗，或一剂，两剂或三剂9价疫苗。一剂2价疫苗组（中位年龄10岁[IQR 9-12]）的154名（99%）参与者和一剂9价疫苗组（中位年龄10岁[IQR 9 -12]）的152名（98%）参与者接种了疫苗并参加了24个月访视，因此被纳入分析。CVT的115名单剂量接受者（中位年龄21岁[19-23]）和IARC印度试验的139名单剂量接受者（中位年龄14岁[13-16]）被纳入分析。接种后24个月，HPV 16 IgG抗体的GMC为22.9国际单位（IU）/mL（95% CI 19.9 - 26.4; n=148），DoRIS 2价疫苗组vs 17.7 IU/mL（13·9-22·5; n=97）CVT（GMC比1.30 [95% CI 1.00 - 1.68]）和13.7 IU/mL（11.9 - 15.8; n=145），而IARC印度试验（GMC比率2.05 [1.61 - 2.61]）为6.7 IU/mL（5.5 - 8.2; n=131）。HPV 18 IgG抗体的GMC为9.9 IU/mL（95% CI 8.5 - 11.5：n=141），DoRIS 2价疫苗组vs 8.0 IU/mL（6·4-10·0; n=97）CVT试验（GMC比1.23 [95% CI 0.95 - 1.60]）和5.7 IU/mL（4.9 - 6.8; n=136），而IARC印度试验为2.2 IU/mL（1.9 - 2.7; n=129）（GMC比2.12 [1.59 - 2.83]）。对于HPV 16和HPV 18，每种疫苗均满足抗体GMC的非劣效性。年轻女孩接种一剂HPV疫苗可能会提供足够的保护，防止持续的HPV感染。一剂计划将降低成本，简化疫苗交付，并扩大疫苗的可及性。英国国际发展部/英国医学研究理事会/惠康信托联合全球健康试验计划，比尔和梅林达盖茨基金会和美国国家癌症研究所。摘要的斯瓦希里语翻译见补充材料部分。
Human papillomavirus (HPV) vaccines are given as a two-dose schedule in children aged 9–14 years, or as three doses in older individuals. We compared antibody responses after one dose of HPV vaccine in the Dose Reduction Immunobridging and Safety Study (DoRIS), a randomised trial of different HPV vaccine schedules in Tanzania, to those from two observational HPV vaccine trials that found high efficacy of one dose up to 11 years against HPV16 and HPV18 (Costa Rica Vaccine Trial [CVT] and Institutional Agency for Research on Cancer [IARC] India trial). In this immunobridging analysis of an open-label randomised controlled trial, girls were recruited from 54 government schools in Mwanza, Tanzania, into the DoRIS trial. Girls were eligible if they were aged 9–14 years, healthy, and HIV negative. Participants were randomly assigned (1:1:1:1:1:1), using permutated block sizes of 12, 18, and 24, to one, two, or three doses of the 2-valent vaccine (Cervarix, GSK Biologicals, Rixensart, Belgium) or the 9-valent vaccine (Gardasil 9, Sanofi Pasteur MSD, Lyon, France). For this immunobridging analysis, the primary objective was to compare geometric mean concentrations (GMCs) at 24 months after one dose in the per-protocol population compared with in historical cohorts: the one-dose 2-valent vaccine group in DoRIS was compared with recipients of the 2-valent vaccine Cervarix from CVT and the one-dose 9-valent vaccine group in DoRIS was compared with recipients of the 4-valent vaccine Gardasil (Merck Sharp & Dohme, Whitehouse Station, NJ, USA) from the IARC India trial. Samples were tested together with virus-like particle ELISA for HPV16 and HPV18 IgG antibodies. Non-inferiority of GMC ratios (DoRIS trial vs historical cohort) was predefined as when the lower bound of the 95% CI was greater than 0·50. This study is registered with ClinicalTrials.gov, NCT02834637. Between Feb 23, 2017, and Jan 6, 2018, we screened 1002 girls for eligibility, of whom 930 were enrolled into DoRIS and 155 each were assigned to one dose, two doses, or three doses of 2-valent vaccine, or one dose, two doses, or three doses of 9-valent vaccine. 154 (99%) participants in the one-dose 2-valent vaccine group (median age 10 years [IQR 9–12]) and 152 (98%) in the one-dose 9-valent vaccine group (median age 10 years [IQR 9–12]) were vaccinated and attended the 24 month visit, and so were included in the analysis. 115 one-dose recipients from the CVT (median age 21 years [19–23]) and 139 one-dose recipients from the IARC India trial (median age 14 years [13–16]) were included in the analysis. At 24 months after vaccination, GMCs for HPV16 IgG antibodies were 22·9 international units (IU) per mL (95% CI 19·9–26·4; n=148) for the DoRIS 2-valent vaccine group versus 17·7 IU/mL (13·9–22·5; n=97) for the CVT (GMC ratio 1·30 [95% CI 1·00–1·68]) and 13·7 IU/mL (11·9–15·8; n=145) for the DoRIS 9-valent vaccine group versus 6·7 IU/mL (5·5–8·2; n=131) for the IARC India trial (GMC ratio 2·05 [1·61–2·61]). GMCs for HPV18 IgG antibodies were 9·9 IU/mL (95% CI 8·5–11·5: n=141) for the DoRIS 2-valent vaccine group versus 8·0 IU/mL (6·4–10·0; n=97) for the CVT trial (GMC ratio 1·23 [95% CI 0·95–1·60]) and 5·7 IU/mL (4·9–6·8; n=136) for the DoRIS 9-valent vaccine group versus 2·2 IU/mL (1·9–2·7; n=129) for the IARC India trial (GMC ratio 2·12 [1·59–2·83]). Non-inferiority of antibody GMCs was met for each vaccine for both HPV16 and HPV18. One dose of HPV vaccine in young girls might provide sufficient protection against persistent HPV infection. A one-dose schedule would reduce costs, simplify vaccine delivery, and expand access to the vaccine. UK Department for International Development/UK Medical Research Council/Wellcome Trust Joint Global Health Trials Scheme, The Bill & Melinda Gates Foundation, and the US National Cancer Institute. For the KiSwahili translation of the abstract see Supplementary Materials section.