Capsid and Genome Modification Strategies to Reduce the Immunogenicity of Adenoviral Vectors
Open Access
- 27 February 2021
- journal article
- review article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (5), 2417
- https://doi.org/10.3390/ijms22052417
Abstract
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.Keywords
This publication has 106 references indexed in Scilit:
- Merck Ad5/HIV induces broad innate immune activation that predicts CD8 + T-cell responses but is attenuated by preexisting Ad5 immunityProceedings of the National Academy of Sciences, 2012
- Serotype-Specific Neutralizing Antibody Epitopes of Human Adenovirus Type 3 (HAdV-3) and HAdV-7 Reside in Multiple Hexon Hypervariable RegionsJournal of Virology, 2012
- Identification of Adenovirus Serotype 5 Hexon Regions That Interact with Scavenger ReceptorsJournal of Virology, 2012
- Adenovirus Serotype 5 Neutralizing Antibodies Target both Hexon and Fiber following Vaccination and Natural InfectionJournal of Virology, 2012
- Modifications of Adenovirus Hexon Allow for Either Hepatocyte Detargeting or Targeting With Potential Evasion From Kupffer CellsMolecular Therapy, 2011
- Atomic Structure of Human Adenovirus by Cryo-EM Reveals Interactions Among Protein NetworksScience, 2010
- Crystal Structure of Human Adenovirus at 3.5 Å ResolutionScience, 2010
- Activation of a dendritic cell–T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cellsThe Journal of Experimental Medicine, 2008
- Comparative Seroprevalence and Immunogenicity of Six Rare Serotype Recombinant Adenovirus Vaccine Vectors from Subgroups B and DJournal of Virology, 2007
- TLR9 signals after translocating from the ER to CpG DNA in the lysosomeNature Immunology, 2004