在布基纳法索成年人中进行的差异化佐剂 Pfs48/45 疟疾疫苗的首次人体 I 期随机试验。

BACKGROUNDMalaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another.METHODSThe candidates R0.6C and ProC6C share the 6C domain of the Plasmodium falciparum sexual-stage antigen Pfs48/45. R0.6C utilizes the glutamate-rich protein (GLURP) as a carrier, and ProC6C includes a second domain (Pfs230-Pro) and a short 36-amino acid circumsporozoite protein (CSP) sequence. Healthy adults (n = 125) from a malaria-endemic area of Burkina Faso were immunized with 3 intramuscular injections, 4 weeks apart, of 30 μg or 100 μg R0.6C or ProC6C each adsorbed to Alhydrogel (AlOH) adjuvant alone or in combination with Matrix-M (15 μg or 50 μg, respectively). The allocation was random and double-blind for this phase I trial.RESULTSThe vaccines were safe and well tolerated with no vaccine-related serious adverse events. A total of 7 adverse events, mild to moderate in intensity and considered possibly related to the study vaccines, were recorded. Vaccine-specific antibodies were highest in volunteers immunized with 100 μg ProC6C-AlOH with Matrix-M, and 13 of 20 (65%) individuals in the group showed greater than 80% transmission-reducing activity (TRA) when evaluated in the standard membrane feeding assay at 15 mg/mL IgG. In contrast, R0.6C induced sporadic TRA.CONCLUSIONAll formulations were safe and well tolerated in a malaria-endemic area of Africa in healthy adults. The ProC6C-AlOH/Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation.TRIAL REGISTRATIONPan-African Clinical Trials Registry (https://pactr.samrc.ac.za) PACTR202201848463189.FUNDINGThe study was funded by the European and Developing Countries Clinical Trials Partnership (grant RIA2018SV-2311).

背景：疟疾传播阻断疫苗旨在阻断疟疾在人与人之间的传播。

方法：候选疫苗 R0.6C 和 ProC6C 共享恶性疟原虫有性期抗原 Pfs48/45 的 6C 结构域。R0.6C 利用富含谷氨酸的蛋白（GLURP）作为载体，ProC6C 包含第二个结构域（Pfs230-Pro）和一个短的 36 个氨基酸的环子孢子蛋白（CSP）序列。来自布基纳法索疟疾流行地区的 125 名健康成年人接受了 3 次肌肉注射，间隔 4 周，每次注射 30μg 或 100μg 的 R0.6C 或 ProC6C，每种疫苗都与氢氧化铝（AlOH）佐剂单独或与 Matrix-M（分别为 15μg 或 50μg）联合吸附。对于这项 I 期试验，分配是随机的，也是双盲的。

结果：疫苗安全且耐受性良好，没有与疫苗相关的严重不良事件。共记录了 7 起不良事件，强度为轻度至中度，认为可能与研究疫苗有关。在标准膜喂养试验中，在 15mg/mL IgG 下，用 100μg ProC6C-AlOH 与 Matrix-M 免疫的志愿者中，疫苗特异性抗体最高，20 名志愿者中有 13 名（65%）的传播减少活性（TRA）大于 80%。相比之下，R0.6C 诱导了零星的 TRA。

结论：在非洲疟疾流行地区，所有配方在健康成年人中均安全且耐受性良好。ProC6C-AlOH/Matrix-M 疫苗引起的功能性抗体水平最高，值得进一步研究。

试验注册：泛非临床试验注册中心（https://pactr.samrc.ac.za）PACTR202201848463189。

资金来源：该研究由欧洲和发展中国家临床试验伙伴关系（grant RIA2018SV-2311）资助。