Interaction of adenovirus with antibodies, complement, and coagulation factors

Adenovirus (AdV) is one of the most widely used vectors for gene therapy and vaccine studies due to its excellent transduction efficiency, capacity for large transgenes, and high levels of gene expression. When administered intravascularly, the fate of AdV vectors is heavily influenced by interactions with host plasma proteins. Some plasma proteins can neutralize AdV, but AdV can also specifically bind plasma proteins that protect against neutralization and preserve activity. This review summarizes the plasma proteins that interact with AdV, including antibodies, complement, and vitamin K-dependent coagulation factors. We will also review the complex interactions of these plasma proteins with each other and with cellular proteins, as well as strategies for developing better AdV vectors that evade or manipulate plasma proteins.