Abstract
Since the early 2000s, adenoviral vectors have been extensively used for the development of infectious disease vaccines. The first clinical vectors were derived from species C human adenovirus type 5 (HAdV-C5) and induced robust T cell and antibody responses against the encoded antigen. However, with widespread prevalence of HAdV-C5 in the human population, pre-existing immunity against the vector often adversely impacts vaccine immunogenicity. To circumvent this, rare human types and nonhuman types have been evaluated as vaccine vectors. Impressively, over 50 adenoviral vectored vaccines have been clinically evaluated against a wide range of pathogens, exploring different dosing regimens and delivery routes. In 2014, the first adenovirus-based vaccine was licensed, utilizing a vector derived from HAdV-D26, a rare human species D adenovirus with low seroprevalence. This adenoviral vector is delivered in a heterologous prime-boost regimen with Modified Vaccinia Ankara vector for prophylaxis against Ebola virus disease. Multiple clinical adenoviral vectored vaccines have since been granted marketing authorization. This success and subsequent widespread administration of adenoviral vectored vaccines is an additional source of antivector immunity, alongside that generated through natural adenovirus infection. This further drives the necessity to understand the mechanisms and impacts of antivector immunity, in addition to developing approaches to negate these. This chapter outlines the breadth of clinical adenoviral vectored vaccines developed against viral, parasitic and bacterial pathogens of humans, defining the clinical needs and associated challenges of such vaccines. The highlights and limitations of these adenoviral vectored vaccines are summarized, alongside vector delivery routes and dosing regimens, populations included during clinical evaluation, vaccine immunogenicity and efficacy outcomes, and the efforts to identify correlates of vaccine-induced protection.