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Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches
Published on: May 6, 2015
Novel adenovirus vectors 'capsid-displaying' a human complement inhibitor
Sergey S Seregin1, Zachary C Hartman, Daniel M Appledorn
1Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48823, USA.
Journal of Innate Immunity
|April 9, 2010
Summary
Novel Adenovirus (Ad) vectors displaying a complement-regulatory peptide (COMPinh) significantly reduce toxicities. This innovation enhances the safety and potential of Ad-based gene transfer for human applications.
Area of Science:
- Gene Therapy
- Virology
- Immunology
Background:
- Adenovirus (Ad) vectors are widely used for human gene transfer.
- Innate, complement-dependent toxicities limit the efficacy of current Ad vectors.
- Novel strategies are needed to improve Ad vector safety and broaden applications.
Purpose of the Study:
- To engineer novel Ad5-based vectors displaying a complement-regulatory peptide (COMPinh).
- To evaluate the ability of these modified vectors to minimize complement activation.
- To assess the potential of COMPinh-displaying Ad5 vectors for safer gene transfer.
Main Methods:
- Construction of Ad5 vectors with capsid-displayed fusion proteins (fiber or pIX) encoding COMPinh.
- Assessment of complement activation using various assays in human and non-human primate systems.
- Evaluation of Ad-dependent innate toxicities.
Main Results:
- Novel Ad5 vectors displaying COMPinh significantly reduced Ad-dependent activation of complement systems.
- Reduced activation was observed in both human and non-human primate complement systems.
- The engineered vectors demonstrated minimized innate toxicities.
Conclusions:
- COMPinh-displaying Ad5 vectors represent a promising advancement in Ad vector technology.
- These novel vectors have the potential to broaden the safe application of gene transfer in humans.
- Further development could lead to enhanced Ad-based therapeutic strategies.
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