Journal article

Targeting the hepatitis B virus precore antigen with a novel IgNAR single variable domain intrabody

Renae Walsh, Stewart Nuttall, Peter Revill, Danni Colledge, Liza Cabuang, Sally Soppe, Olan Dolezal, Kate Griffiths, Angeline Bartholomeusz, Stephen Locarnini



The Hepatitis B virus precore protein is processed in the endoplasmic reticulum (ER) into secreted hepatitis B e antigen (HBeAg), which acts as an immune tolerogen to establish chronic infection. Downregulation of secreted HBeAg should improve clinical outcome, as patients who effectively respond to current treatments (IFN-α) have significantly lower serum HBeAg levels. Here, we describe a novel reagent, a single variable domain (V(NAR)) of the shark immunoglobulin new antigen receptor (IgNAR) antibodies. V(NAR)s possess advantages in stability, size (~14 kDa) and cryptic epitope recognition compared to conventional antibodies. The V(NAR) domain displayed biologically useful affinity for rec..

View full abstract


Funding Acknowledgements

We thank Ms Vanessa Hughes, Ms Julie Angerosa and Ms Meghan Hattaki for the technical assistance with this research. We thank Mr Nick Bartone for the oligonucleotide synthesis and Mr Phil Strike for the N-terminal protein sequencing. The Co-operative Research Centre for Diagnostics is acknowledged for their partial financial support of this work, as is the Bristol-Myers Squibb Freedom to discover award to Stephen Locarnini.