冈比亚医学研究委员会Ed Clarke团队研究了麻疹和风疹疫苗微针贴剂的疗效与安全性。这一研究成果发表在2024年4月29日出版的《柳叶刀》杂志上。

在中低收入国家，微针贴片被列为克服免疫障碍的全球最高优先创新。该试验旨在提供麻疹和风疹疫苗（MRV）-MNP在儿童中的耐受性、安全性和免疫原性的第一批数据。

这项单中心、1/2期、双盲、双模拟、随机、主动对照、年龄递减试验在冈比亚进行。为了获得资格，所有参与者必须根据预先指定的标准保持健康，成人队列的年龄为18-40岁，幼儿的年龄为15-18个月，婴儿的年龄为9-10个月，并且在整个随访期内可以就诊。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（美光生物医学，美国佐治亚州亚特兰大）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）。非盲工作人员使用在线应用程序随机分配参与者，他们制备了视觉上相同的MRV-MNP或安慰剂MNP制剂和MRV-SC或安慰剂SC制剂，但没有参与收集终点数据。管理研究干预措施的工作人员、参与者、家长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。免疫原性人群包括所有接种疫苗的参与者，他们有基线和第42天的访视结果，并且没有被认为会对免疫原性终点产生重大影响的方案偏差。在接种疫苗后的14天内收集引起的局部和全身不良事件。收集到第180天的未经请求的不良事件。队列之间的年龄降级是基于独立数据监测委员会对截至第14天的安全数据的审查。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、血清保护和血清转化率以及几何平均抗体浓度。

招募时间为2021年5月18日至2022年5月27日。45名成年人、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，没有任何安全问题，年龄相应下降。在婴儿中，MRV-MNP给药后，93%（52/56；95%CI 83.0-97.2）血清转化为麻疹，100%（58/58；93.8-100）血清转化成风疹，而MRV-SC给药后分别有90%（52/58；79.2-95.2）和100%（59/59；93.9-100）血清转为麻疹和风疹。60名幼儿中有46名（77%）和60名婴儿中有39名（65%）出现在MRV-MNP应用部位的局部反应（最为常见）。在接受MRV-MNP的60名幼儿中有35名（58%）和60名婴儿中有57名（95%）报告了相关的未经请求的不良事件，最常见的是在应用部位变色。所有局部反应均为轻度。没有相关的严重或严重不良事件。

研究结果表明，安全性和免疫原性数据支持MRV-MNP的加速开发。

附：英文原文

Title: A measles and rubella vaccine microneedle patch in The Gambia: a phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial

Author: Ikechukwu Adigweme, Mohammed Yisa, Michael Ooko, Edem Akpalu, Andrew Bruce, Simon Donkor, Lamin B Jarju, Baba Danso, Anthony Mendy, David Jeffries, Anne Segonds-Pichon, Abdoulie Njie, Stephen Crooke, Elina El-Badry, Hilary Johnstone, Michael Royals, James L Goodson, Mark R Prausnitz, Devin V McAllister, Paul A Rota, Sebastien Henry, Ed Clarke

Issue&Volume: 2024-04-29

Abstract:

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.

DOI: 10.1016/S0140-6736(24)00532-4

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00532-4/abstract