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Encapsulation of recombinant adenovirus into alginate microspheres circumvents vector-specific immune response

Gene Therapy volume 9, pages 1722–1729 (2002)Cite this article

Abstract

Pre-existing immunity against adenoviruses may compromise the efficacy of adenoviral vectors for vaccination and gene therapy. The purpose of this study was to determine whether encapsulation of adenovirus recombinants into biodegradable alginate microparticles could circumvent the vector-specific immune response. Mice were immunized either intranasally (i.n.) or intraperitoneally (i.p.) with human adenovirus type 5 (HAd5), resulting in the development of virus-specific antibodies. Immunized and naı¨ve mice were inoculated with AdCA36lacZ (an E1-deleted HAd5 recombinant containing the bacterial β-galactosidase (LacZ) gene), encapsulated (E) into alginate microparticles, or nonencapsulated (NE) ie, as a virus suspension. LacZ expression in animals immunized once (1×) or twice (2×) with HAd5 and subsequently inoculated with NE-AdCA36lacZ (NE-Z) was significantly (P<0.001) reduced compared to those levels observed in NE-Z inoculated naı¨ve mice, suggesting that the immune response against the vector adversely affected transgene expression. In contrast, there was only slight reduction (P>0.05) in LacZ expression in mice immunized 1× or 2× with HAd5 that were subsequently inoculated with E-AdCA36lacZ (E-Z) compared to those levels obtained in E-Z inoculated naı¨ve animals. Similar results were obtained with i.n. or i.p. inoculated animals. These results indicate that microencapsulation of recombinant adenovirus effectively circumvented the vector-specific immune response.

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Acknowledgements

We thank Dr FL Graham, Departments of Biology and Pathology, McMaster University, Hamilton, Ontario, Canada for providing AdCA36lacZ and Jane Kovach for excellent secretary assistance. This work was supported by Public Health Service grant GM5516 from NIH/NIGMS to SKM

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Author notes

  1. G Sailaja

    Present address: Vaccine Research Center at Yerkes, 954 Gatewood Road, Emory University, Atlanta, GA 30329, USA

  2. J Hays

    Present address: , 6100 Maple Forest Road, West Point, IN 47992, USA

Authors and Affiliations

  1. Department of Veterinary Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, IN, USA

    G Sailaja, H HogenEsch, A North & S K Mittal

  2. Laboratory Animal Program, Purdue University, West Lafayette, IN, USA

    J Hays

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Sailaja, G., HogenEsch, H., North, A. et al. Encapsulation of recombinant adenovirus into alginate microspheres circumvents vector-specific immune response. Gene Ther 9, 1722–1729 (2002). https://doi.org/10.1038/sj.gt.3301858

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  • DOI: https://doi.org/10.1038/sj.gt.3301858

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