1887

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Volume 88, Issue 11

High-level expression from two independent expression cassettes in replication-incompetent adenovirus type 35 vector Free

Abstract

Replication-incompetent adenovirus type 35 (rAd35) represents a potent vaccine carrier that elicits strong, antigen-specific T- and B-cell responses in diverse preclinical models. Moreover, Ad35 is rare in human populations, resulting in the absence of neutralizing antibodies against this carrier, in contrast to the commonly used rAd5. Therefore, rAd35 is being investigated as a vaccine carrier for a number of diseases for which an effective vaccine is needed, including malaria, AIDS and tuberculosis. However, it can be perceived that effective immunization will require insertion of multiple antigens into adenoviral vectors. We therefore wanted to create rAd35 vectors carrying double expression cassettes, to expand within one vector the number of insertion sites for foreign DNA encoding antigenic proteins. We show that it is possible to generate rAd35 vectors carrying two cytomegalovirus promoter-driven expression cassettes, provided that the polyadenylation signals in each expression cassette are not identical. We demonstrate excellent rAd35 vector stability and show that expression of a transgene is not influenced by the presence of a second expression cassette. Moreover, by using two model vaccine antigens, i.e. the human immunodeficiency virus-derived Env-gp120 protein and the -derived circumsporozoite protein, we demonstrate that potent T- and B-cell responses are induced to both antigens expressed from a single vector. Such rAd35 vectors thus expand the utility of rAd35 vaccine carriers for the development of vaccines against, for example, malaria, AIDS and tuberculosis.

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  • Accepted:
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2007-11-01
2024-04-26
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References

  1. Basler C. F., Horwitz M. S. 1996; Subgroup B adenovirus type 35 early region 3 mRNAs differ from those of the subgroup C adenoviruses. Virology 215:165–177 [CrossRef]
     [Google Scholar]
  2. Bauzon M., Castro D., Karr M., Hawkins L. K., Hermiston T. W. 2003; Multigene expression from a replicating adenovirus using native viral promoters. Mol Ther 7:526–534 [CrossRef]
     [Google Scholar]
  3. Belousova N., Harris R., Zinn K., Rhodes-Selser M. A., Kotov A., Kotova O., Wang M., Aurigemma R., Zhu Z. B. other authors 2006; Circumventing recombination events encountered with production of a clinical-grade adenoviral vector with a double-expression cassette. Mol Pharmacol 70:1488–1493 [CrossRef]
     [Google Scholar]
  4. Bennekov T., Dietrich J., Rosenkrands I., Stryhn A., Doherty T. M., Andersen P. 2006; Alteration of epitope recognition pattern in Ag85B and ESAT-6 has a profound influence on vaccine-induced protection against Mycobacterium tuberculosis . Eur J Immunol 36:3346–3355 [CrossRef]
     [Google Scholar]
  5. Berenjian S., Akusjarvi G. 2006; Binary AdEasy vector systems designed for Tet-ON or Tet-OFF regulated control of transgene expression. Virus Res 115:16–23 [CrossRef]
     [Google Scholar]
  6. Bett A. J., Haddara W., Prevec L., Graham F. L. 1994; An efficient and flexible system for construction of adenovirus vectors with insertions or deletions in early regions 1 and 3. Proc Natl Acad Sci U S A 91:8802–8806 [CrossRef]
     [Google Scholar]
  7. Bramson J., Hitt M., Gallichan W. S., Rosenthal K. L., Gauldie J., Graham F. L. 1996; Construction of a double recombinant adenovirus vector expressing a heterodimeric cytokine: in vitro and in vivo production of biologically active interleukin-12. Hum Gene Ther 7:333–342 [CrossRef]
     [Google Scholar]
  8. Catanzaro A. T., Koup R. A., Roederer M., Bailer R. T., Enama M. E., Moodie Z., Gu L., Martin J. E., Novik L. other authors 2006; Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 candidate vaccine delivered by a replication-defective recombinant adenovirus vector. J Infect Dis 194:1638–1649 [CrossRef]
     [Google Scholar]
  9. Danthinne X., Werth E. 2000; New tools for the generation of E1- and/or E3-substituted adenoviral vectors. Gene Ther 7:80–87 [CrossRef]
     [Google Scholar]
  10. Fallaux F. J., Bout A., van der Velde I., van den Wollenberg D. J., Hehir K. M., Keegan J., Auger C., Cramer S. J., van Ormondt H. other authors 1998; New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses. Hum Gene Ther 9:1909–1917 [CrossRef]
     [Google Scholar]
  11. Ghosh-Choudhury G., Haj-Ahmad Y., Brinkley P., Rudy J., Graham F. L. 1986; Human adenovirus cloning vectors based on infectious bacterial plasmids. Gene 50:161–171 [CrossRef]
     [Google Scholar]
  12. Gonzalez-Nicolini V., Fussenegger M. 2005; A novel binary adenovirus-based dual-regulated expression system for independent transcription control of two different transgenes. J Gene Med 7:1573–1585 [CrossRef]
     [Google Scholar]
  13. Havenga M., Vogels R., Zuijdgeest D., Radosevic K., Mueller S., Sieuwerts M., Weichold F., Damen I., Kaspers J. other authors 2006; Novel replication-incompetent adenoviral B-group vectors: high vector stability and yield in PER.C6 cells. J Gen Virol 87:2135–2143 [CrossRef]
     [Google Scholar]
  14. He T. C., Zhou S., da Costa L. T., Yu J., Kinzler K. W., Vogelstein B. 1998; A simplified system for generating recombinant adenoviruses. Proc Natl Acad Sci U S A 95:2509–2514 [CrossRef]
     [Google Scholar]
  15. Huang Y., Kong W. P., Nabel G. J. 2001; Human immunodeficiency virus type 1-specific immunity after genetic immunization is enhanced by modification of Gag and Pol expression. J Virol 75:4947–4951 [CrossRef]
     [Google Scholar]
  16. Karlsson G. B., Halloran M., Li J., Park I. W., Gomila R., Reimann K. A., Axthelm M. K., Iliff S. A., Letvin N. L., Sodroski J. 1997; Characterization of molecularly cloned simian-human immunodeficiency viruses causing rapid CD4+ lymphocyte depletion in rhesus monkeys. J Virol 71:4218–4225
     [Google Scholar]
  17. Lee K. H., Kim H. K., Paik J. Y., Matsui T., Choe Y. S., Choi Y., Kim B. T. 2005; Accuracy of myocardial sodium/iodide symporter gene expression imaging with radioiodide: evaluation with a dual-gene adenovirus vector. J Nucl Med 46:652–657
     [Google Scholar]
  18. Liu J., Ewald B. A., Lynch D. M., Nanda A., Sumida S. M., Barouch D. H. 2006; Modulation of DNA vaccine-elicited CD8+ T-lymphocyte epitope immunodominance hierarchies. J Virol 80:11991–11997 [CrossRef]
     [Google Scholar]
  19. Murakami P., Pungor E., Files J., Do L., Van Rijnsoever R., Vogels R., Bout A., McCaman M. 2002; A single short stretch of homology between adenoviral vector and packaging cell line can give rise to cytopathic effect-inducing, helper-dependent E1-positive particles. Hum Gene Ther 13:909–920 [CrossRef]
     [Google Scholar]
  20. Nanda D., Vogels R., Havenga M., Avezaat C. J., Bout A., Smitt P. S. 2001; Treatment of malignant gliomas with a replicating adenoviral vector expressing herpes simplex virus-thymidine kinase. Cancer Res 61:8743–8750
     [Google Scholar]
  21. Putzer B. M., Hitt M., Muller W. J., Emtage P., Gauldie J., Graham F. L. 1997; Interleukin 12 and B7-1 costimulatory molecule expressed by an adenovirus vector act synergistically to facilitate tumor regression. Proc Natl Acad Sci U S A 94:10889–10894 [CrossRef]
     [Google Scholar]
  22. Rodriguez F., Harkins S., Slifka M. K., Whitton J. L. 2002; Immunodominance in virus-induced CD8+ T-cell responses is dramatically modified by DNA immunization and is regulated by gamma interferon. J Virol 76:4251–4259 [CrossRef]
     [Google Scholar]
  23. Steinwaerder D. S., Carlson C. A., Lieber A. 1999; Generation of adenovirus vectors devoid of all viral genes by recombination between inverted repeats. J Virol 73:9303–9313
     [Google Scholar]
  24. Toapanta F. R., Craigo J. K., Montelaro R. C., Ross T. M. 2007; Reduction of anti-HIV-1 Gag immune responses during co-immunization: immune interference by the HIV-1 envelope. Curr HIV Res 5:199–209 [CrossRef]
     [Google Scholar]
  25. Vellinga J., Van der Heijdt S., Hoeben R. C. 2005; The adenovirus capsid: major progress in minor proteins. J Gen Virol 86:1581–1588 [CrossRef]
     [Google Scholar]
  26. Yewdell J. W., Bennink J. R. 1999; Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses. Annu Rev Immunol 17:51–88 [CrossRef]
     [Google Scholar]
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High-level expression from two independent expression cassettes in replication-incompetent adenovirus type 35 vector
J. Gen. Virol. 88, 2915 (2007); https://doi.org/10.1099/vir.0.83119-0
/content/journal/jgv/10.1099/vir.0.83119-0
/content/journal/jgv/10.1099/vir.0.83119-0
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