Novel targeted anti-amoebic strategies using Nanobody technology

Acanthamoeba keratitis (AK) is a serious eye infection linked to contact lens (CL) wearers, with the risk of permanent blindness. The main causative pathogenic agent, the amoeba Acanthamoeba castellanii, has now been classified as an emerging parasite due to the confirmed global increase of AK infections. Safe and efficient compounds for AK prevention and treatment are still lacking today.
The current therapeutics (not approved by the FDA nor the EMA) require long-term treatment periods (leading to amoebal resistance) and are not specific, generating important toxicity for human corneal cells and resulting in permanent eye damage. Therefore, novel targeted and safe therapeutics against AK are needed, especially against the resilient cyst form. In this project, I will generate new anti-amoebic strategies by impeding encystment. To do this, I will generate Nanobodies (Nbs) that bind specifically on surface-exposed antigens of A. castellanii. These Nbs will be tested for their direct inhibitory effect on encystation. In addition, preliminary data suggest that impairing encystment using cellulases leads to an important anti-amoebic effect. Thus, Nbs will also be fused to several cellulases to generate the first targeted therapeutics against AK, which will be tested in vitro on relevant clinical isolates from AK patients and in vivo using the validated rat infection model for AK. This project will contribute to filling the gaps in the diagnostics,
prevention, and therapy of AK.