Strategies to Overcome the Action of Neutralizing Antibodies Against AAV

Time: 11:30 am
day: Day Two


  • Neutralizing antibodies are the first host barrier of defence against wild type AAVs. Most of the recombinant AAV capsids used for gene therapies are
    identical or similar to those of wild type AAVs and their transduction if blocked by preexisting neutralizing antibodies
  • Immune complexes of rAAV bound by IgG or IgM can trigger the complement pathway, amplifying capsid immune responses upon rAAV systemic administration being one potential consequence is thrombotic microangiopathy (TMA)
  • There are several strategies under investigation to overcome this first barrier and unwanted side effects including plasmapheresis and immunoadsorption, empty capsids as decoys, column-based capsid-specific removal, immunoglobulin type G (IgG)-cleaving endopeptidases like IdeS or IdeZ or capsid engineering to modify or replace the epitopes targeted by neutralizing antibodies