Teaching an old vector new tricks: the surprising versatility of AAV vaccines

Adeno-associated virus (AAV) has proven its clinical efficacy in the realm of gene therapy, resulting in seven FDA-approved gene therapies. While AAV gene transfer research has predominantly focused on its utility in monogenic disorders, AAV vectors have been used as a platform for vaccines in over 50 preclinical studies over the last 25 years. Recombinant AAV-based vaccines have demonstrated induction and durability of antigen-specific adaptive immune responses in a variety of preclinical models. This mini-review serves as a comprehensive discussion of the basics of vaccine vector design and experimental considerations, highlighting engineering efforts to improve AAV vaccine efficacy, along with the known advantages and disadvantages of AAV-based vaccines from published pre-clinical studies.