Capsid and Genome Modification Strategies to Reduce the Immunogenicity of Adenoviral Vectors

Adenovirus-based gene transfer vectors are the most frequently used vector type in gene therapy clinical trials to date, and they play an important role as genetic vaccine candidates during the ongoing SARS-CoV-2 pandemic. Immediately upon delivery, adenovirus-based vectors exhibit multiple complex vector-host interactions and induce innate and adaptive immune responses. This can severely limit their safety and efficacy, particularly after delivery through the blood stream. In this review article we summarize two strategies to modulate Ad vector-induced immune responses: extensive genomic and chemical capsid modifications. Both strategies have shown beneficial effects in a number of preclinical studies while potential synergistic effects warrant further investigations.

Automated summary

Adenovirus-based gene transfer vectors are widely used in gene therapy clinical trials and as genetic vaccine candidates during the SARS-CoV-2 pandemic. Immune responses induced by these vectors can be modulated through extensive genomic and chemical capsid modifications, with potential synergistic effects that require further investigation in preclinical studies.