Single-dose genetically attenuated malaria vaccine
Building on the shoulders of several decades of molecular malaria research at LUMC, the team has now developed a prototype for a single-dose malaria vaccine using a malaria parasite that holds a single gene knock-out (GA2). They showed that this parasite is not only safe to administer to human (>50 people immunized) but can also protect healthy malaria-naïve adults with a single mosquito-bite administered dose. The research now focuses on the translatability of these findings into a malaria vaccine with preliminary research into malaria sporozoite purification, immune mechanisms of protection and potential next-generation prototypes.
Malaria hepatocyte biology
The development of malaria parasites in the liver, specifically liver cells (hepatocytes) is considered the “black hole” of a well-characterised parasite lifecycle. Yet this life stage is a very attractive therapeutic target (as evidenced by our own GA2 parasites which arrest during this stage). Under the guidance and supervision of Dr. A.S.P. Yang, the team aims to 1) discover novel parasite biology during liver stage development and 2) understand host responses against this parasite in both infected and surrounding uninfected hepatocytes. The host model used here is quite unique and consist of primary human hepatocytes isolated from leftover segments from liver surgeries. Together, this will create an unique window into the interaction between malaria parasites and human liver (a normally inaccessible organ of the human body), allowing us to develop novel therapies (vaccines and/or drugs) against this ancient parasite.
Innovative Diagnostic Research
Our group combines decades of expertise in teaching in clinical parasitology with advanced research on diagnostic tools for human parasitic infections, focusing primarily on schistosomiasis and soil-transmitted helminths (Dr. Lisette van Lieshout). We develop, implement, and evaluate platforms such as nucleic acid amplification techniques (PCR, LAMP), digital microscopy solutions, and immunoassays for Schistosoma circulating antigens (CCA and CAA), in close collaboration with departmental colleagues (Dr. Pystje Hoekstra, Dr. Govert van Dam, Prof. Dr. Ron Hokke). These diagnostic tools are applied in epidemiological studies, intervention monitoring, and assessments of new drug and vaccine candidates, with strong emphasis on quality assurance and diagnostic accuracy. In-depth research addresses complex clinical syndromes, including male and female genital schistosomiasis. All activities are embedded in international collaborations, largely with the Global South, aiming to advance reliable diagnostics for global health.
Schistosome immunology
Within the team we are working to understand immune response to schistosome worms. A key aspect of this is understanding immune responses in controlled human schistosome infection models (Dr. E.L. Houlder). We work collaboratively with other groups in the department to do this in a high-dimensional and integrated way. Findings from controlled human infection models in Leiden are compared to endemic populations (E. Driciru). Finally, our work uses in vitro models to assess schistosome motility (E. Iliopoulou), immune interactions, and develop novel therapeutic and preventative tools (Dr. E.L. Houlder).
