Targeting the hepatitis B virus precore antigen with a novel IgNAR single variable domain intrabody Academic Article uri icon

abstract

  • 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 recombinant and native HBeAg, and recognised a unique conformational epitope. To assess therapeutic potential in targeting intracellular precore protein to reduce secreted HBeAg, the V(NAR) was engineered for ER-targeted in vitro delivery to function as an intracellular antibody (intrabody). In vitro data from HBV/precore hepatocyte cell lines demonstrated effective intrabody regulation of precore/HBeAg.

authors

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

publication date

  • March 2011