Advances in the design of adenoviral vectored vaccines

Replication-incompetent AdV vaccine vectors have a demonstrated ability to induce potent antigen-specific immune responses and an acceptable safety profile in humans. Several immunization schedules have currently been tested in clinical trials; single or multiple doses of an AdV based vaccine followed by a single or multiple dose of an alternative vector (e.g. AdV or MVA), a mixture of monovalent AdV vectors, or an AdV prime combined with (adjuvanted) protein/virus-like particle (VLP) boost. While these schedules have resulted in potent immunity with a favorable safety profile, they may be complex for general implementation after licensure. Advances in the design of AdV vector vaccines offer several alternatives: AdV vectors engineered to display an antigen on the outer capsid surface, functioning much like a VLP vaccine to induce B-cell antigen-specific immune responses. Unlike a typical VLP platform, AdV antigen-display vectors induce potent immune responses without the need for an adjuvant. Importantly, AdV antigen-display vectors can be designed to genetically encode specific antigens. The AdV genome can further be engineered to genetically encode more than one antigen resulting in a ‘multivalent’ vector. This thesis focuses on advancing the design of AdV vectors as vaccines against infectious diseases.