Development of a controlled human infection model for schistosomiasis and transfer of this model to Uganda
At CHIC we dedicate a large part of our efforts to advancing our understanding and the development of vaccines to combat schistosomiasis. The production of eggs by the paired Schistosoma mansoni worm in the mesenteric venules causes damage to the surrounding tissue, affecting the lives of hundreds of millions of people around the world. We have developed protocols and molecular tools to produce the Schistosoma mansoni larvae (cercariae) of only one sex (male or female). These single-sex cercariae can develop into adult worms within their hosts but cannot produce eggs. Having investigated these infections in animal models first, we subsequently developed a controlled human infection model for single-sex schistosomes (both a male and a female model) through the exposure of healthy individuals to low numbers of infectious cercariae. Novel diagnostic tools developed by Dr. Govert van Dam and Dr. Paul Corstjens allowed us to detect the infection over time with a highly sensitive lateral flow assay (upconverting phosphor lateral flow assay for detection of circulating anodic antigen).
We now proceeded to also test the immune response after repeated infection with male schistosoma mansoni cercariae in healthy volunteers. This study is ongoing, for up-to-date information on the recruitment of volunteers, please refer to https://controlledhumaninfectionscentre.com/ Dr. Emma Houlder leads a research program to identify antigen specific responses from these controlled infection studies which may serve as future vaccine candidates.
Recently, CHIC has embarked on a long-term collaboration with Prof. Elliott at the Ugandan Virus Research Institute (UVRI), to transfer the technology of controlled human infections for schistosomiasis to Entebbe, at the lakeshore of lake Victoria where schistosomiasis is endemic. In addition, CHIC has dedicated efforts to test the Smp80 vaccine, one of the most promising vaccines against Schistosoma mansoni, developed by Prof. Siddiqui at Texas Tech University Health Sciences Center in a clinical trial using its controlled human infection model. This study is funded by the Wellcome Trust.
Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings.
Driciru E, Koopman JPR, Cose S, Siddiqui AA, Yazdanbakhsh M, Elliott AM, Roestenberg M.Front Immunol. 2021 Mar 4;12:635985. doi: 10.3389/fimmu.2021.635985. eCollection 2021.
Controlled human infection models to evaluate schistosomiasis and hookworm vaccines: where are we now?
Koopman JPR, Driciru E, Roestenberg M.Expert Rev Vaccines. 2021 Nov;20(11):1369-1371. doi: 10.1080/14760584.2021.1951244. Epub 2021 Jul 15.
Katayama Syndrome Without Schistosoma mansoni Eggs.
Langenberg MCC, Hoogerwerf MA, Janse JJ, van Lieshout L, Corstjens PLAM, Roestenberg M; CoHSI clinical trial team.Ann Intern Med. 2019 May 21;170(10):732-733. doi: 10.7326/L18-0438. Epub 2019 Jan 8.
A controlled human Schistosoma mansoni infection model to advance novel drugs, vaccines and diagnostics.
Langenberg MCC, Hoogerwerf MA, Koopman JPR, Janse JJ, Kos-van Oosterhoud J, Feijt C, Jochems SP, de Dood CJ, van Schuijlenburg R, Ozir-Fazalalikhan A, Manurung MD, Sartono E, van der Beek MT, Winkel BMF, Verbeek-Menken PH, Stam KA, van Leeuwen FWB, Meij P, van Diepen A, van Lieshout L, van Dam GJ, Corstjens PLAM, Hokke CH, Yazdanbakhsh M, Visser LG, Roestenberg M.Nat Med. 2020 Mar;26(3):326-332. doi: 10.1038/s41591-020-0759-x. Epub 2020 Feb 17.