The immunogenicity and safety of adenoviral-based vaccines

Human adenoviruses (HAdVs) have shown promise as versatile and effective delivery vectors for vaccine development. This was highlighted during the COVID-19 pandemic, which demonstrated the importance of effective vaccines but also provided scope to explore potential limitations of current viral-vector based strategies. This review summarizes the current applications of adenoviral vectors, in addition to discussing the immunological mechanisms underpinning immunogenicity and safety of viral vector-based vaccines.

Clinical trials involving HAdVs have been undertaken to combat a range of infectious diseases, such as SARS-CoV-2, Ebola and HIV-1. However, empirical evidence indicates that preexisting T-cell immunity to adenoviruses may occur independent of serological exposure, predominantly arising from the conserved nature of immunogenic hexon proteins. As a result, T-cell responses are frequently detectable and often demonstrate broad cross-reactivity between human and nonhuman adenovirus (AdV) serotypes. Adverse events to vaccination are rare, although thrombotic events and severe cutaneous adverse reactions have been reported.

Antivector T-cell immunogenicity arising from preexisting viral exposure or T-cell cross-reactivity may influence vaccine-specific immune responses. Continuous iterative refinement within the development of new vaccine vector technologies is therefore essential to circumvent limitations associated with vector-specific T-cell responses. However, mechanistic insight on the role of T-cells within pathomechanisms of adverse events remains unclear.