Abaasa Andrew, Egesa Moses, Driciru Emmanuella, Koopman Jan Pieter R, Kiyemba Ronald, Sanya Richard E, Nassuuna Jacent, Ssali Agnes, Kimbugwe Geofrey, Wajja Anne, van Dam Govert J, Corstjens Paul L A M, Cose Stephen, Seeley Janet, Kamuya Dorcas, Webb Emily L, Yazdanbakhsh Maria, Kaleebu Pontiano, Siddiqui Afzal A, Kabatereine Narcis, Tukahebwa Edridah, Roestenberg Meta, Elliott Alison M
MRC/UVRI & LSHTM Uganda Research Unit, Entebbe, Uganda.
London School of Hygiene & Tropical Medicine, London, UK.
Immunother Adv. 2023 Jul 20;3(1):ltad010. doi: 10.1093/immadv/ltad010. eCollection 2023.
Control of schistosomiasis depends on a single drug, praziquantel, with variable cure rates, high reinfection rates, and risk of drug resistance. A vaccine could transform schistosomiasis control. Preclinical data show that vaccine development is possible, but conventional vaccine efficacy trials require high incidence, long-term follow-up, and large sample size. Controlled human infection studies (CHI) can provide early efficacy data, allowing the selection of optimal candidates for further trials. A CHI has been established in the Netherlands but responses to infection and vaccines differ in target populations in endemic countries. We aim to develop a CHI for in Uganda to test candidate vaccines in an endemic setting. This is an open-label, dose-escalation trial in two populations: minimal, or intense, prior exposure. In each population, participants will be enrolled in sequential dose-escalating groups. Initially, three volunteers will be exposed to 10 cercariae. If all show infection, seven more will be exposed to the same dose. If not, three volunteers in subsequent groups will be exposed to higher doses (20 or 30 cercariae) following the same algorithm, until all 10 volunteers receiving a particular dose become infected, at which point the study will be stopped for that population. Volunteers will be followed weekly after infection until CAA positivity or to 12 weeks. Once positive, they will be treated with praziquantel and followed for one year. The trial registry number is ISRCTN14033813 and all approvals have been obtained. The trial will be subjected to monitoring, inspection, and/or audits.
血吸虫病的防控依赖于单一药物吡喹酮，其治愈率各异，再感染率高且存在耐药风险。疫苗有望改变血吸虫病的防控局面。临床前数据表明疫苗研发具有可行性，但传统的疫苗疗效试验需要高发病率、长期随访以及大样本量。人体感染对照研究（CHI）能够提供早期疗效数据，从而筛选出进一步试验的最佳候选疫苗。荷兰已开展了一项人体感染对照研究，但在血吸虫病流行国家，目标人群对感染和疫苗的反应存在差异。我们旨在在乌干达开展人体感染对照研究，以便在流行环境中测试候选疫苗。这是一项针对两类人群的开放标签、剂量递增试验：既往暴露程度最低或最高。在每类人群中，参与者将按顺序纳入剂量递增组。最初，三名志愿者将接触10只尾蚴。若所有人均显示感染，将再增加七名志愿者接触相同剂量。若并非如此，后续组中的三名志愿者将按照相同算法接触更高剂量（20只或30只尾蚴），直至接受特定剂量的所有10名志愿者均被感染，届时该人群的研究将停止。感染后，志愿者将每周接受随访，直至循环阳极抗原（CAA）呈阳性或至12周。一旦呈阳性，他们将接受吡喹酮治疗并随访一年。试验注册号为ISRCTN14033813，且已获得所有批准。该试验将接受监测、检查和/或审计。
