Data for: A Phase 1b, open-label, age de-escalation, dose-escalation study to evaluate the safety and immunogenicity of different doses of a candidate malaria vaccine; adjuvanted R21(R21/MM) in adults, young children and infants in Kilifi, Kenya

In the era of anti-malaria drug resistance and resistance to insecticide treated bed nets, there is an urgent need for a highly efficacious vaccine. We evaluated a candidate malaria vaccine incorporating the antigen R21 (part of the P. falciparum circumsporozoite malaria antigen co-expressed with hepatitis B antigen plus an adjuvant to boost the immune responses (Matrix-M). R21c/Matrix-M showed promising safety and immunogenicity data in preclinical and early phase trials in Oxford. We conducted an open label, age de-escalation, dose escalation study in 20 healthy adults (18-45 years), 20 young children aged 1-5 years and 51 infants aged 5- <12 months. Each participant was screened to ensure they were in good health based on clinical assessment and laboratory results. Participants had a blood test to ensure suitability prior to vaccination. For each participant, there was a total of 31 visits to the clinic and at home, 15 of which were associated with blood sampling (38 visits for those in the booster phase). Participants recieved 3 vaccinations 4 weeks apart. Blood tests and clinical assessments were conducted to screen out participants with health conditions that may have impacted participants or study outcomes. Bloods were taken at screening and a day prior to enrolment. Blood were also taken prior to each vaccination and on days 2 and 7 post vaccination at the clinic for the primary series ( 3 doses). Home visits were conducted on days 1, 3, 4, 5, and 6 to identify solicited adverse events. Bloods for immunology were taken prior to vaccination, and throughout the study to assess the immune response to R21/Matrix-M. In addition, we invited participants to receive a booster vaccine at 9-25 months after receipt of the 3rd vaccine of R21/Matrix-M and took bloods in clinic 28 days after boosting with field workers supporting participants or their parents/guardians to do this over the phone. During the booster vaccination visit (4th dose_, the participants/Parents/guardians were guided through the measurement of body temperature, assessment of the vaccination site (for redness, swelling and erythema) and documentation of the results on the diary card. They were then issued with a thermometer, vaccination ruler, a copy of the diary card and a pen to facilitate the completion of the remote safety assessments.

在疟原虫对抗疟药物产生耐药性、蚊虫对抗杀虫剂处理蚊帐产生耐药性的当下，全球亟需一款高效的疟疾疫苗。本研究对一款候选疟疾疫苗展开评估，该疫苗包含抗原R21——该抗原属于恶性疟原虫（P. falciparum）环子孢子疟疾抗原的组分，与乙型肝炎抗原共表达，并辅以佐剂Matrix-M以增强免疫应答。R21c/Matrix-M疫苗在牛津开展的临床前及早期临床试验中，已展现出良好的安全性与免疫原性数据。

本研究开展了一项开放标签、年龄递减、剂量递增的临床试验，共纳入20名健康成人（18~45岁）、20名1~5岁的幼儿以及51名5~<12个月的婴儿。所有受试者均需通过临床评估与实验室检测完成筛查，以确认健康状况良好；并在疫苗接种前接受血液检测，以确认符合入组要求。每名受试者总计需完成31次临床与居家随访，其中15次伴随血液采样；加强免疫阶段的受试者则需完成38次随访。受试者需间隔4周完成3剂次疫苗接种。

研究过程中还将通过血液检测与临床评估，排查可能影响受试者安全或研究结果的健康状况异常者。受试者需在筛查阶段及入组前1天完成血液采样；基础免疫阶段（3剂次）的血液采样分别于每次接种前、接种后第2天及第7天在临床机构完成。研究人员会在接种后第1、3、4、5、6天开展居家随访，以识别主动上报的不良事件。研究全程会在每次接种前采集血液样本用于免疫学检测，以评估受试者对R21/Matrix-M的免疫应答水平。

此外，本研究邀请受试者在完成第3剂R21/Matrix-M疫苗接种后的9~25个月接种加强针，并于加强免疫后28天在临床机构完成血液采样；外勤研究人员会通过电话协助受试者或其监护人完成相关流程。在加强免疫（第4剂）随访期间，研究人员会指导受试者或其监护人完成体温测量、接种部位评估（观察红斑、肿胀与红斑疹），并将结果记录在日志卡上。随后研究人员会为受试者或其监护人发放体温计、接种部位测量尺、日志卡副本及笔，以协助其完成远程安全评估。