# Functionally-derivatized Nanoantibodies as novel tools for Giardia lamblia cyst detection

## TL;DR

Researchers developed affordable nanoantibodies to detect Giardia parasites, which could improve diagnostics in resource-limited areas.

## Contribution

The study introduces the first nanoantibodies specifically targeting Giardia lamblia cysts for diagnostic use.

## Key findings

- Twelve unique nanoantibodies with strong binding affinity to Giardia cysts were developed and characterized.
- Nanoantibodies offer a cost-effective and scalable alternative to current diagnostic methods for Giardia.
- This work pioneers the use of nanoantibodies for intestinal parasite diagnostics, previously unexplored for Giardia.

## Abstract

Giardia lamblia (syn. intestinalis, duodenalis) is the causative agent of Giardiasis, a diarrheal disease of global medical importance, especially problematic in young children living in unhygienic, resource-constrained settings. Diagnostics of potential Giardia infections are generally done through classic light-microscopy stool examination. This is often insufficient, and ELISA-based fluorescence detection using costly proprietary reagents is employed. These reagents are often not affordable in contexts where they are needed the most, and this limits their use to resource-rich settings where Giardiasis is rarely problematic. To address these issues in medical equity while designing novel strategies to investigate the Giardia cyst wall, we report on the development and characterisation of alpaca derived single-domain antibodies, known as nanoantibodies, elicited against G. lamblia enriched cyst-wall preparations. We evaluated the effectiveness and binding capacity of twelve unique E. coli-produced recombinant nanoantibody sequences for Giardia cyst wall detection and provide proof of concept for the effectiveness and versatility of these protein domains.

As a globally distributed intestinal parasite, Giardia lamblia causes 300 million cases of water-borne diarrheal disease per year, a scourge of underserved and neglected populations, and especially problematic in young children. Giardia detection relies on laborious microscopy-based analysis of faecal samples, often coupled to antibody-based detection of coproantigen using costly proprietary reagents which are not routinely affordable in the areas hardest hit by this parasitic infection. The availability of cost-effective and locally produced diagnostics tools for giardiasis would be of great advantage, especially in resource-limited settings. To begin to address these issues in global diagnostics equity, this work reports on the development and characterization of a set of twelve unique Nanoantibody (Nab) sequences, with specific and strong binding affinity to Giardia cysts both in vivo and in vitro. Nabs can be cheaply produced and scaled up without the need for expensive equipment, animal housing facilities and animal sacrifice. To our knowledge, the only other Nabs developed for parasite diagnostics target Trypanosoma cruzi, making this work a first in terms of novel diagnostic tools for intestinal parasites of global medical relevance.