The Immune System—A Double-Edged Sword for Adenovirus-Based Therapies

Rebecca Wallace, Carly M. Bliss, Alan L. Parker

Research output: Contribution to journalReview articlepeer-review


Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine, and oncology applications, Ad-based platforms offer advantages, including ease of genetic manipulation, scale of production, and well-established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that must be overcome for adenovirus-based therapies to be truly efficacious. Both pre-existing anti-Ad immunity in the population as well as the rapid development of an immune response against engineered adenoviral vectors can have detrimental effects on the downstream impact of an adenovirus-based therapeutic. This review focuses on the different challenges posed, including pre-existing natural immunity and anti-vector immunity induced by a therapeutic, in the context of innate and adaptive immune responses. We summarise different approaches developed with the aim of tackling these problems, as well as their outcomes and potential future applications.

Original languageEnglish
Article number973
Issue number6
StatePublished - Jun 2024
Externally publishedYes


  • adenovirus
  • antibody
  • evasion
  • immunity
  • seroprevalence
  • T cell
  • vector


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