Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania; Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania.
Lancet Glob Health. 2022 Oct;10(10):e1473-e1484. doi: 10.1016/S2214-109X(22)00309-6.
An estimated 15% of girls aged 9-14 years worldwide have been vaccinated against human papillomavirus (HPV) with the recommended two-dose or three-dose schedules. A one-dose HPV vaccine schedule would be simpler and cheaper to deliver. We report immunogenicity and safety results of different doses of two different HPV vaccines in Tanzanian girls.
In this open-label, randomised, phase 3, non-inferiority trial, we enrolled healthy schoolgirls aged 9-14 years from Government schools in Mwanza, Tanzania. Eligible participants were randomly assigned to receive one, two, or three doses of either the 2-valent vaccine (Cervarix, GSK Biologicals, Rixensart) or the 9-valent vaccine (Gardasil-9, Sanofi Pasteur MSD, Lyon). The primary outcome was HPV 16 specific or HPV 18 specific seropositivity following one dose compared with two or three doses of the same HPV vaccine 24 months after vaccination. Safety was assessed as solicited adverse events up to 30 days after each dose and unsolicited adverse events up to 24 months after vaccination or to last study visit. The primary outcome was done in the per-protocol population, and safety was analysed in the total vaccinated population. This study was registered in ClinicalTrials.gov, NCT02834637.
Between Feb 23, 2017, and Jan 6, 2018, we screened 1002 girls for eligibility. 72 girls were excluded. 930 girls were enrolled and randomly assigned to receive one dose of Cervarix (155 participants), two doses of Cervarix (155 participants), three doses of Cervarix (155 participants), one dose of Gardasil-9 (155 participants), two doses of Gardasil-9 (155 participants), or three doses of Gardasil-9 (155 participants). 922 participants received all scheduled doses within the defined window (three withdrew, one was lost to follow-up, and one died before completion; two received their 6-month doses early, and one received the wrong valent vaccine in error; all 930 participants were included in the total vaccinated cohort). Retention at 24 months was 918 (99%) of 930 participants. In the according-to-protocol cohort, at 24 months, 99% of participants who received one dose of either HPV vaccine were seropositive for HPV 16 IgG antibodies, compared with 100% of participants who received two doses, and 100% of participants who received three doses. This met the prespecified non-inferiority criteria. Anti-HPV 18 seropositivity at 24 months did not meet non-inferiority criteria for one dose compared to two doses or three doses for either vaccine, although more than 98% of girls in all groups had HPV 18 antibodies. 53 serious adverse events (SAEs) were experienced by 42 (4·5%) of 930 girls, the most common of which was hospital admission for malaria. One girl died of malaria. Number of events was similar between groups and no SAEs were considered related to vaccination.
A single dose of the 2-valent or 9-valent HPV vaccine in girls aged 9-14 years induced robust immune responses up to 24 months, suggesting that this reduced dose regimen could be suitable for prevention of HPV infection among girls in the target age group for vaccination.
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.
全球约有 15%的 9-14 岁女孩接种了人乳头瘤病毒（HPV）疫苗，采用的是推荐的两剂或三剂方案。一剂 HPV 疫苗方案的接种实施将更加简单且成本更低。我们报告了不同剂量的两种不同 HPV 疫苗在坦桑尼亚女孩中的免疫原性和安全性结果。
这是一项开放标签、随机、3 期、非劣效性试验，我们招募了来自坦桑尼亚姆万扎政府学校的 9-14 岁健康女学生。符合条件的参与者被随机分配接受二价疫苗（Cervarix，GSK 生物制品，里克斯纳特）或九价疫苗（Gardasil-9，赛诺菲巴斯德 MSD，里昂）的一剂、两剂或三剂。主要终点是与接种同一种 HPV 疫苗两剂或三剂相比，接种一剂 HPV 16 型或 HPV 18 型特异性血清阳性率，接种后 24 个月进行评估。安全性评估为每次接种后 30 天内的自我报告不良事件和接种后 24 个月内或最后一次研究访问的自我报告不良事件。主要终点在符合方案人群中进行，安全性在总接种人群中进行分析。本研究在 ClinicalTrials.gov 注册，NCT02834637。
2017 年 2 月 23 日至 2018 年 1 月 6 日期间，我们对 1002 名女孩进行了筛选，以确定其是否符合条件。72 名女孩被排除在外。930 名女孩入组并随机分配接受一剂 Cervarix（155 名参与者）、两剂 Cervarix（155 名参与者）、三剂 Cervarix（155 名参与者）、一剂 Gardasil-9（155 名参与者）、两剂 Gardasil-9（155 名参与者）或三剂 Gardasil-9（155 名参与者）。922 名参与者在规定的时间窗口内接种了所有计划剂量（3 名退出，1 名失访，1 名死亡前未完成，2 名提前接种了 6 个月剂量，1 名接种了错误的价疫苗；所有 930 名参与者均纳入总接种队列）。24 个月时的保留率为 930 名参与者中的 918 名（99%）。在符合方案的队列中，接种一剂 HPV 疫苗的 99%的参与者在 24 个月时 HPV 16 IgG 抗体呈阳性，而接种两剂 HPV 疫苗的参与者为 100%，接种三剂 HPV 疫苗的参与者为 100%。这符合预先指定的非劣效性标准。尽管两组中超过 98%的女孩都有 HPV 18 抗体，但与两剂或三剂相比，一剂疫苗对 HPV 18 的血清阳性率在 24 个月时不满足非劣效性标准。930 名女孩中有 42 名（4.5%）经历了 53 例严重不良事件（SAE），其中最常见的是疟疾住院。一名女孩死于疟疾。各组之间的事件数量相似，没有 SAE 被认为与接种有关。
9-14 岁女孩接种一剂二价或九价 HPV 疫苗可在 24 个月内诱导出强大的免疫应答，这表明该减少剂量方案可能适用于该目标年龄组女孩 HPV 感染的预防。
英国国际发展部/英国医学研究理事会/惠康信托联合全球卫生试验计划、比尔和梅琳达盖茨基金会以及美国国家癌症研究所。
Zotero 插件
