Identification of effective single-domain antibodies against the malaria sporozoite using a synthetic single-domain antibody library with unconventional diversification strategies

Malaria, caused by Plasmodium parasites, is one of the ‘Big Three’ infectious diseases, together with HIV and TB. Each year more than 200 million cases of the disease are documented, including more than half a million deaths (>76% of the deceased are children under the age of five). Problems are worsened due to low-efficacy vaccines, drug-resistant parasites and the (re-)emergence of the disease around the globe. This clearly indicates that novel intervention strategies are still direly needed. Antibodies (Abs) are potent tools for parasite neutralisation. Besides conventional Abs, the natural immune repertoire of mammals contains so-called unconventional diversification strategies, which extend the coverage of antigen space. Interestingly, unconventional Abs appear to excel in neutralising highly sophisticated pathogens. Camelid single-domain Abs (sdAbs) are prime examples of such unconventional Ab fragments. Extensive knowledge on the camelid sdAb structure-function relationship enables the construction of highly diverse synthetic libraries that offer several advantages over immune libraries obtained through immunisation. This project aims to harness the potential of synthetic sdAb libraries with unconventional diversification strategies to tackle the malaria sporozoite through an interdisciplinary research approach combining molecular, structural, and parasitological methods.

Project Details

Basic Science
Vaccines (Immune Correlates)

Nov 2023 — Oct 2027

Belgium