Koopman Jan Pieter R, Houlder Emma L, Janse Jacqueline J, Lamers Olivia Ac, Roozen Geert Vt, Sijtsma Jeroen C, Casacuberta-Partal Miriam, Hilt Stan T, van der Stoep M Y Eileen C, van Amerongen-Westra Inge M, Brienen Eric At, Wammes Linda J, van Lieshout Lisette, van Dam Govert J, Corstjens Paul Lam, van Diepen Angela, Yazdanbakhsh Maria, Hokke Cornelis H, Roestenberg Meta
Leiden University Center for Infectious Diseases.
Department of Cell and Chemical Biology.
J Clin Invest. 2024 Dec 12;135(4):e185422. doi: 10.1172/JCI185422.
BACKGROUNDPartial protective immunity to schistosomiasis develops over time, following repeated praziquantel (PZQ) treatment. Moreover, animals develop protective immunity after repeated immunization with irradiated cercariae. Here, we evaluated the development of natural immunity through consecutive exposure-treatment cycles with Schistosoma mansoni in healthy, Schistosoma-naive participants using single-sex, controlled human S. mansoni infection.METHODSTwenty-four participants were randomized in a double-blinded (1:1) manner to either the reinfection group, which received 3 exposures (weeks 0, 9, and 18) to 20 male cercariae, or to the infection control group, which received 2 mock exposures with water (weeks 0 and 9) prior to cercariae exposure (week 18). Participants were treated with PZQ (or placebo) at weeks 8, 17, and 30. Attack rates (ARs) after the final exposure (weeks 19-30) using serum circulating anodic antigen (CAA) positivity were compared between groups. Adverse events (AEs) were collected for safety.RESULTSTwenty-three participants completed the follow-up. No protective efficacy was observed, given an 82% (9 of 11) AR after the final exposure in the reinfection group and 92% (11 of 12) in the infection control group (protective efficacy 11%; 95% CI -24% to 35%; P = 0.5). Related AEs were higher after the first infection (45%) compared with the second (27%) and third (28%) infections. Severe acute schistosomiasis was observed after the first infections only (2 of 12 in the reinfection group and 2 of 12 in the infection control group).CONCLUSIONRepeated Schistosoma exposure and treatment cycles resulted in apparent clinical tolerance, with fewer symptoms reported following subsequent infections, but did not result in protection against reinfection.TRIAL REGISTRATIONClinicalTrials.gov NCT05085470.FUNDINGEuropean Research Council (ERC) Starting Grant (no. 101075876).
随着时间推移，在反复使用吡喹酮（PZQ）治疗后，对血吸虫病会产生部分保护性免疫。此外，动物在经辐照尾蚴反复免疫后会产生保护性免疫。在此，我们通过在健康的、未感染过血吸虫的参与者中使用单性别、受控的曼氏血吸虫人体感染，通过连续的暴露-治疗周期来评估自然免疫的发展情况。
24名参与者以双盲（1:1）方式随机分为再感染组，该组接受3次（第0、9和18周）每次20条雄性尾蚴的暴露，或感染对照组，该组在尾蚴暴露（第18周）前接受2次用水的模拟暴露（第0和9周）。参与者在第8、17和30周接受PZQ（或安慰剂）治疗。比较两组在最后一次暴露（第19 - 30周）后使用血清循环阳极抗原（CAA）阳性的攻击率（ARs）。收集不良事件（AEs）以评估安全性。
23名参与者完成了随访。未观察到保护效果，再感染组最后一次暴露后的攻击率为82%（11例中的9例），感染对照组为92%（12例中的11例）（保护效果为11%；95%置信区间为 -24%至35%；P = 0.5）。第一次感染后的相关不良事件（45%）高于第二次（27%）和第三次（28%）感染。仅在第一次感染后观察到严重急性血吸虫病（再感染组12例中的2例，感染对照组12例中的2例）。
反复的血吸虫暴露和治疗周期导致明显的临床耐受性，后续感染后报告的症状较少，但并未产生抗再感染的保护作用。
ClinicalTrials.gov NCT05085470。
欧洲研究理事会（ERC）启动基金（编号101075876）。
