本文由小咖机器人翻译整理

期刊来源：Lancet

原文链接：https://doi.org/10.1016/S0140-6736(24)00532-4

摘要内容如下：

背景

微针贴片（MNP）已被列为克服低收入和中等收入国家免疫障碍的全球最优先创新。该试验旨在首次提供关于麻疹和风疹疫苗（MRV）-MNP在儿童中的耐受性、安全性和免疫原性的数据。

方法

这项单中心、1/2期、双盲、双模拟、随机、活性对照、年龄递减试验在冈比亚进行。根据预先指定的标准，所有参与者必须健康，成人队列年龄为18-40岁，幼儿年龄为15-18个月，婴儿年龄为9-10个月，并在整个随访期内可接受访问。三个年龄组以2:1的比例（成人）或1:1的比例（幼儿和婴儿）随机分配接受MRV-MNP（Micron Biomedical，Atlanta，GA，USA）和安慰剂（0.9%氯化钠）皮下注射，或安慰剂-MNP和MRV皮下注射（MRV-SC；印度血清研究所，印度浦那）。未蒙面的工作人员兰塞姆使用在线应用程序分配参与者，他们准备了MRV-MNP或安慰剂-MNP和MRV-SC或安慰剂-SC的视觉上相同的制剂，但不参与收集终点数据。管理研究干预措施的工作人员、参与者、父母和评估试验终点的研究工作人员对治疗分配不知情。安全人群由所有接种疫苗的参与者组成，并根据MRV给药途径进行分析，而不考虑随后的方案偏差。免疫原性人群由所有接种疫苗的参与者组成，这些参与者具有可用的基线和第42天访视结果，并且没有被认为会显著影响免疫原性终点的方案偏差。在接种疫苗后14天内收集局部和全身不良事件。未经请求的不良事件收集至第180天。队列之间的年龄递减基于独立数据监测委员会对第14天安全性数据的审查。在基线、第42天和第180天测量麻疹和风疹的血清中和抗体。分析是描述性的，包括安全性事件、血清保护和血清转换率以及抗体浓度的几何平均值。该试验已在泛非临床试验注册中心PACTR202008836432905注册，并已完成。

调查结果

招募于2021年5月18日至2022年5月27日进行。45名成人、120名幼儿和120名婴儿被随机分配并接种疫苗。在成人或幼儿接种疫苗后的前14天内，没有出现安全问题，年龄下降也相应进行。婴儿为93%（52/56）；95%可信区间（CI）83.0~97.2）血清转化为麻疹和100%（58/58；注射MRV-MNP后，90%（52/58）血清转化为风疹病毒；79.2-95.2）和100%（59/59；93.9-100）分别转化为麻疹和风疹。MRV-MNP应用部位的硬结是60名幼儿中46名（77%）和60名婴儿中39名（65%）最常见的局部反应。接受MRV-MNP的60名幼儿中有35名（58%）和60名婴儿中有57名（95%）报告了相关的主动不良事件，最常见的是用药部位变色。所有局部反应轻微。没有相关的严重或严重不良事件。

解释

安全性和免疫原性数据支持MRV-MNP的加速发展。

英文原文如下：

Abstracts

BACKGROUND  Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries. This trial aimed to provide the first data on the tolerability, safety, and immunogenicity of a measles and rubella vaccine (MRV)-MNP in children.

METHODS  This single-centre, phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial was conducted in The Gambia. To be eligible, all participants had to be healthy according to prespecified criteria, aged 18-40 years for the adult cohort, 15-18 months for toddlers, or 9-10 months for infants, and to be available for visits throughout the follow-up period. The three age cohorts were randomly assigned in a 2:1 ratio (adults) or 1:1 ratio (toddlers and infants) to receive either an MRV-MNP (Micron Biomedical, Atlanta, GA, USA) and a placebo (0·9% sodium chloride) subcutaneous injection, or a placebo-MNP and an MRV subcutaneous injection (MRV-SC; Serum Institute of India, Pune, India). Unmasked staff ransomly assigned the participants using an online application, and they prepared visually identical preparations of the MRV-MNP or placebo-MNP and MRV-SC or placebo-SC, but were not involved in collecting endpoint data. Staff administering the study interventions, participants, parents, and study staff assessing trial endpoints were masked to treatment allocation. The safety population consists of all vaccinated participants, and analysis was conducted according to route of MRV administration, irrespective of subsequent protocol deviations. The immunogenicity population consisted of all vaccinated participants who had a baseline and day 42 visit result available, and who had no protocol deviations considered to substantially affect the immunogenicity endpoints. Solicited local and systemic adverse events were collected for 14 days following vaccination. Unsolicited adverse events were collected to day 180. Age de-escalation between cohorts was based on the review of the safety data to day 14 by an independent data monitoring committee. Serum neutralising antibodies to measles and rubella were measured at baseline, day 42, and day 180. Analysis was descriptive and included safety events, seroprotection and seroconversion rates, and geometric mean antibody concentrations. The trial was registered with the Pan African Clinical Trials Registry PACTR202008836432905, and is complete.

FINDINGS  Recruitment took place between May 18, 2021, and May 27, 2022. 45 adults, 120 toddlers, and 120 infants were randomly allocated and vaccinated. There were no safety concerns in the first 14 days following vaccination in either adults or toddlers, and age de-escalation proceeded accordingly. In infants, 93% (52/56; 95% CI 83·0-97·2) seroconverted to measles and 100% (58/58; 93·8-100) seroconverted to rubella following MRV-MNP administration, while 90% (52/58; 79·2-95·2) and 100% (59/59; 93·9-100) seroconverted to measles and rubella respectively, following MRV-SC. Induration at the MRV-MNP application site was the most frequent local reaction occurring in 46 (77%) of 60 toddlers and 39 (65%) of 60 infants. Related unsolicited adverse events, most commonly discolouration at the application site, were reported in 35 (58%) of 60 toddlers and 57 (95%) of 60 infants that had received the MRV-MNP. All local reactions were mild. There were no related severe or serious adverse events.

INTERPRETATION  The safety and immunogenicity data support the accelerated development of the MRV-MNP.

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