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Vaccine Design: Replication-Defective Adenovirus Vectors

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Vaccine Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1404))

Abstract

Replication-defective adenovirus (Ad) vectors were initially developed for gene transfer for correction of genetic diseases. Although Ad vectors achieved high levels of transgene product expression in a variety of target cells, expression of therapeutic proteins was found to be transient as vigorous T cell responses directed to components of the vector as well as the transgene product rapidly eliminate Ad vector-transduced cells. This opened the use of Ad vectors as vaccine carriers and by now a multitude of preclinical as well as clinical studies has shown that Ad vectors induce very potent and sustained transgene product-specific T and B cell responses. This chapter provides guidance on developing E1-deleted Ad vectors based on available viral molecular clones. Specifically, it describes methods for cloning, viral rescue and purification as well as quality control studies.

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References

  1. Xiang ZQ, Yang Y, Wilson JM, Ertl HC (1996) A replication-defective human adenovirus recombinant serves as a highly efficacious vaccine carrier. Virology 219:220–227

    Article  CAS  Google Scholar 

  2. Xiang ZQ, Greenberg L, Ertl HC (2014) Rupprecht CE (2014) Protection of non-human primates against rabies with an adenovirus recombinant vaccine. Virology 450–451:243–249

    Article  Google Scholar 

  3. Colloca S, Barnes E, Folgori A et al (2012) Vaccine vectors derived from a large collection of simian adenoviruses induce potent cellular immunity across multiple species. Sci Transl Med 4:115ra2

    Article  Google Scholar 

  4. Ledgerwood JE, Costner P, Desai N, VRC 205 Study Team (2010) A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. Vaccine 29:304–313

    Article  CAS  Google Scholar 

  5. Hung PP, Morin JE, Lubeck MD et al (1988) Expression of HBV surface antigen or HIV envelope protein using recombinant adenovirus vectors. Nat Immun Cell Growth Regul 7:135–143

    CAS  PubMed  Google Scholar 

  6. Khanam S, Pilankatta R, Khanna N, Swaminathan S (2009) An adenovirus type 5 (AdV5) vector encoding an envelope domain III-based tetravalent antigen elicits immune responses against all four dengue viruses in the presence of prior AdV5 immunity. Vaccine 27:6011–6021

    Article  CAS  Google Scholar 

  7. Shim BS, Stadler K, Nguyen HH et al (2012) Sublingual immunization with recombinant adenovirus encoding SARS-CoV spike protein induces systemic and mucosal immunity without redirection of the virus to the brain. Virol J 9:215

    Article  CAS  Google Scholar 

  8. Sharma A, Wendland R, Sung B et al (2014) Maternal immunization with chimpanzee adenovirus expressing RSV fusion protein protects against neonatal RSV pulmonary infection. Vaccine 32:5761–5768

    Article  CAS  Google Scholar 

  9. Li K, Li PY, Wu XA et al (2013) Induction of Hantaan virus-specific immune responses in C57BL/6 mice by immunization with a modified recombinant adenovirus containing the chimeric gene, GcS0.7. Int J Mol Med 32:709–716

    Article  CAS  Google Scholar 

  10. Wang Y, Liu C, Xia Q et al (2014) Antitumor effect of adenoviral vector prime protein boost immunity targeting the MUC1 VNTRs. Oncol Rep 31:1437–1444

    Article  CAS  Google Scholar 

  11. Aurisicchio L, Peruzzi D, Koo G et al (2014) Immunogenicity and therapeutic efficacy of a dual-component genetic cancer vaccine cotargeting carcinoembryonic antigen and HER2/neu in preclinical models. Hum Gene Ther 25:121–131

    Article  CAS  Google Scholar 

  12. Pedersen SR, Sørensen MR, Buus S et al (2013) Comparison of vaccine-induced effector CD8 T cell responses directed against self- and non-self-tumor antigens: implications for cancer immunotherapy. J Immunol 191:3955–3967

    Article  CAS  Google Scholar 

  13. Lubaroff DM, Konety BR, Link B et al (2009) Phase I clinical trial of an adenovirus/prostate-specific antigen vaccine for prostate cancer: safety and immunologic results. Clin Cancer Res 15:7375–7380

    Article  CAS  Google Scholar 

  14. Shiver JW, Fu TM, Chen L et al (2002) Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 415:331–335

    Article  CAS  Google Scholar 

  15. Tatsis N, Fitzgerald JC, Reyes-Sandoval A et al (2007) Adenoviral vectors persist in vivo and maintain activated CD8+ T cells: implications for their use as vaccines. Blood 110:1916–1923

    Article  CAS  Google Scholar 

  16. Zhou D, Zhou X, Bian A et al (2010) An efficient method of directly cloning chimpanzee adenovirus as a vaccine vector. Nat Protoc 5:1775–1785

    Article  CAS  Google Scholar 

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Correspondence to Hildegund C. J. Ertl .

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© 2016 Springer Science+Business Media New York

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Zhou, X., Xiang, Z., Ertl, H.C.J. (2016). Vaccine Design: Replication-Defective Adenovirus Vectors. In: Thomas, S. (eds) Vaccine Design. Methods in Molecular Biology, vol 1404. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-3389-1_23

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  • DOI: https://doi.org/10.1007/978-1-4939-3389-1_23

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-3388-4

  • Online ISBN: 978-1-4939-3389-1

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