化学预防疫苗接种：一项探索美国成年人对恶性疟原虫阶段特异性免疫的 I 期研究。
Chemoprophylaxis Vaccination: Phase I Study to Explore Stage-specific Immunity to Plasmodium falciparum in US Adults.
机构信息
Center for Infectious Disease Research, Seattle, Washington, USA.
Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Washington, Seattle, Washington, USA.
出版信息
Clin Infect Dis. 2020 Sep 12;71(6):1481-1490. doi: 10.1093/cid/ciz1010.
BACKGROUND
Chemoprophylaxis vaccination with sporozoites (CVac) with chloroquine induces protection against a homologous Plasmodium falciparum sporozoite (PfSPZ) challenge, but whether blood-stage parasite exposure is required for protection remains unclear. Chloroquine suppresses and clears blood-stage parasitemia, while other antimalarial drugs, such as primaquine, act against liver-stage parasites. Here, we evaluated CVac regimens using primaquine and/or chloroquine as the partner drug to discern whether blood-stage parasite exposure impacts protection against homologous controlled human malaria infection.
METHODS
In a Phase I, randomized, partial double-blind, placebo-controlled study of 36 malaria-naive adults, all CVac subjects received chloroquine prophylaxis and bites from 12-15 P. falciparum-infected mosquitoes (CVac-chloroquine arm) at 3 monthly iterations, and some received postexposure primaquine (CVac-primaquine/chloroquine arm). Drug control subjects received primaquine, chloroquine, and uninfected mosquito bites. After a chloroquine washout, subjects, including treatment-naive infectivity controls, underwent homologous, PfSPZ controlled human malaria infection and were monitored for parasitemia for 21 days.
RESULTS
No serious adverse events occurred. During CVac, all but 1 subject in the study remained blood-smear negative, while only 1 subject (primaquine/chloroquine arm) remained polymerase chain reaction-negative. Upon challenge, compared to infectivity controls, 3/3 chloroquine arm subjects displayed delayed patent parasitemia (P = .01) but not sterile protection, while 3/11 primaquine/chloroquine subjects remained blood-smear negative.
CONCLUSIONS
CVac-primaquine/chloroquine is safe and induces sterile immunity to P. falciparum in some recipients, but a single 45 mg dose of primaquine postexposure does not completely prevent blood-stage parasitemia. Unlike previous studies, CVac-chloroquine did not produce sterile immunity.
CLINICAL TRIALS REGISTRATION
NCT01500980.
背景
用疟原虫孢子（CVac）加氯喹进行化学预防接种可诱导对同源恶性疟原虫孢子（PfSPZ）的挑战产生保护，但血期寄生虫暴露是否对保护产生影响尚不清楚。氯喹可抑制和清除血期寄生虫血症，而其他抗疟药物，如伯氨喹，可作用于肝期寄生虫。在此，我们评估了用伯氨喹和/或氯喹作为联合药物的 CVac 方案，以确定血期寄生虫暴露是否影响对同源性受控人类疟疾感染的保护作用。
方法
在一项针对 36 名疟原虫阴性成年人的 I 期、随机、部分双盲、安慰剂对照研究中，所有 CVac 受试者均接受氯喹预防，并在 3 个月的时间内接受来自 12-15 只感染恶性疟原虫的蚊子叮咬（CVac-氯喹组），一些受试者还接受了暴露后伯氨喹（CVac-伯氨喹/氯喹组）。药物对照受试者接受伯氨喹、氯喹和未感染的蚊子叮咬。在氯喹冲洗后，包括治疗性感染对照组在内的受试者接受同源性 PfSPZ 受控的人类疟疾感染，并监测寄生虫血症 21 天。
结果
无严重不良事件发生。在 CVac 期间，除 1 名研究受试者外，所有受试者的血涂片均为阴性，而只有 1 名受试者（伯氨喹/氯喹组）的聚合酶链反应为阴性。在受到挑战时，与感染对照组相比，3/3 名氯喹组受试者的有症状寄生虫血症出现延迟（P =.01），但未达到无菌保护，而 3/11 名伯氨喹/氯喹组受试者的血涂片仍为阴性。
结论
CVac-伯氨喹/氯喹是安全的，可在一些接受者中诱导对恶性疟原虫的无菌免疫，但单次 45mg 伯氨喹暴露并不能完全预防血期寄生虫血症。与之前的研究不同，CVac-氯喹并未产生无菌免疫。
临床试验注册
NCT01500980。
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