■恶性疟原虫(Pf)子孢子(SPZ)化学预防疫苗(PfSPZ-CVac)涉及同时施用传染性PfSPZ和疟疾药物,通常是氯喹(CQ),杀死肝脏出现的寄生虫.PfSPZ-CVac(CQ)保护了100%的未感染疟疾的参与者免受控制的人类疟疾感染。我们调查了PfSPZ-CVac(CQ)对季节性、暴露于疟疾的成年人的地方性Pf。
■健康的18-45岁青少年参加了双盲,在Bougoula-Hameau进行的安慰剂对照试验,马里,随机1:1至2.048×105PfSPZ(PfSPZ挑战)或生理盐水在0、4、8周直接静脉接种。注射器是由药房工作人员使用随机分配的在线基于计算机的注册准备的。疫苗和安慰剂的外观相同,确保了临床团队和参与者的掩蔽。参与者在首次接种前接受氯喹600mg,疫苗接种期间每周10次300mg剂量,然后在雨季进行24周监测之前,每日7剂青蒿琥酯200mg。安全性结果为注射后12天内征求的不良事件(AE)和相关的非征求的AE,和所有严重的AE。通过每四周进行一次浓稠的血液涂片以及在48周内的高热疾病期间检测到Pf感染。主要疫苗效力(VE)终点是24周时的感染时间。NCT02996695。
■62名参与者于2017年4月/5月注册。经历至少一次系统性AE的参与者比例在治疗组之间相似:6/31(19.4%,95CI9.2-36.3)的PfSPZ-CVac接受者与7/31(22.6%,95CI29.2-62.2)的对照(p值=1.000)。每组有2/31(6%)报告相关,未经请求的AE。发生了一起无关的死亡。在每个方案接受3次免疫的59人中,接种疫苗者(16/29,55.2%)比对照组(22/30,73.3%)少.VE风险比为33.6%(p=0.21,95CI-27·9,65·5),风险比为24.8%(p=0.10,95CI-4·8,54·3)。对PfCSP的抗体反应较差;28%的疫苗接种者血清转化。
■PfSPZ-CVac(CQ)耐受性良好。在这种非常高的传播环境中,测试的给药方案未能显着防止Pf感染。
■美国国立卫生研究院,Sanaria.
■ClinicalTrials.gov标识符(NCT编号):NCT02996695。
UNASSIGNED: Plasmodium falciparum (Pf) Sporozoite (SPZ) Chemoprophylaxis Vaccine (PfSPZ-CVac) involves concurrently administering infectious PfSPZ and malaria drug, often chloroquine (CQ), to kill liver-emerging parasites. PfSPZ-CVac (CQ) protected 100% of malaria-naïve participants against controlled human malaria infection. We investigated the hypothesis that PfSPZ-CVac (CQ) is safe and efficacious against seasonal, endemic Pf in malaria-exposed adults.
UNASSIGNED: Healthy 18-45 year olds were enrolled in a double-blind, placebo-controlled trial in Bougoula-Hameau, Mali, randomized 1:1 to 2.048 × 105 PfSPZ (PfSPZ Challenge) or normal saline administered by direct venous inoculation at 0, 4, 8 weeks. Syringes were prepared by pharmacy staff using online computer-based enrolment that randomized allocations. Clinical team and participant masking was assured by identical appearance of vaccine and placebo. Participants received chloroquine 600mg before first vaccination, 10 weekly 300mg doses during vaccination, then seven daily doses of artesunate 200mg before 24-week surveillance during the rainy season. Safety outcomes were solicited adverse events (AEs) and related unsolicited AEs within 12 days of injections, and all serious AEs. Pf infection was detected by thick blood smears performed every four weeks and during febrile illness over 48 weeks. Primary vaccine efficacy (VE) endpoint was time to infection at 24 weeks. NCT02996695.
UNASSIGNED: 62 participants were enrolled in April/May 2017. Proportions of participants experiencing at least one solicited systemic AE were similar between treatment arms: 6/31 (19.4%, 95%CI 9.2-36.3) of PfSPZ-CVac recipients versus 7/31 (22.6%, 95%CI 29.2-62.2) of controls (p value = 1.000). Two/31 (6%) in each group reported related, unsolicited AEs. One unrelated death occurred. Of 59 receiving 3 immunizations per protocol, fewer vaccinees (16/29, 55.2%) became infected than controls (22/30, 73.3%). VE was 33.6% by hazard ratio (p = 0.21, 95%CI -27·9, 65·5) and 24.8% by risk ratio (p = 0.10, 95%CI -4·8, 54·3). Antibody responses to PfCSP were poor; 28% of vaccinees sero-converted.
UNASSIGNED: PfSPZ-CVac (CQ) was well-tolerated. The tested dosing regimen failed to significantly protect against Pf infection in this very high transmission setting.
UNASSIGNED: U.S. National Institutes of Health, Sanaria.
UNASSIGNED: ClinicalTrials.gov identifier (NCT number): NCT02996695.