WP2: In vitro validation of antibodies

In this workpackage the monoclonal antibodies will be assessed for their ability to neutralise a panel of HCVpp and HCVcc - this will also be assessed in combination, to determine whether or not synergy exists. To define target therapeutic antibody concentrations we will also perform passaging experiments to establish whether or not virus can acquire neutralisation resistance, define the mechanism underlying resistance and also the antibody concentrations at which this can take place. Finally, we will also define the sensitivity of the HCV isolates present in the clinical trial patients to the trail antibodies and also monitor post-transplant re-emergence virus populations (if they ensue) for antibody resistance. To summarise, this workpackage will focus on:

  • In vitro validation of the neutralizing breadth and potency of GLP / GMP lots of monoclonal antibody

  • Assessment of synergy between lead and back-up monoclonal antibodies

  • Definition of target therapeutic doses that minimize the likelihood of resistance

 

Virus neutralization