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Making an Avipoxvirus Encoding a Tumor-Associated Antigen and a Costimulatory Molecule

Part of the Methods in Molecular Biology book series (MIMB,volume 1139)

Abstract

Fowlpox virus (FPV) is a double-stranded DNA virus with a history of use as a live attenuated vaccine in commercial poultry production systems. FPV is also highly amenable to genetic engineering, with a large cloning capacity and many nonessential sites available for integration, meaning that in recombinant form, several transgenes can be expressed simultaneously. Recombinant FPV has proven an effective prophylactic vaccine vector for other diseases of birds, as well as other animal species (Brun et al., Vaccine 26:6508–6528, 2008). These vectors do not integrate into the host genome nor do they undergo productive replication in mammalian cells; thus they have a proven and impeccable safety profile and have been progressed as prophylactic and therapeutic vaccine vectors for use in humans (Beukema et al., Expert Rev Vaccines 5:565–577, 2006; Lousberg et al., Expert Rev Vaccines 10:1435–1449, 2011). Furthermore, repeated immunization with FPV does not blunt subsequent vaccine responses, presumably because it is replication-defective, and thus larger doses can be routinely administered (Brun et al., Vaccine 26:6508–6528, 2008). This strengthens the case for FPV as a viable platform vaccine vector, as it means it can be used repeatedly in an individual to achieve different immunological outcomes. Here we describe in detail the construction of a recombinant variant of FPV expressing the prostate tumor-associated antigen prostatic acid phosphatase (PAP) in conjunction with the immunostimulatory cytokine, interleukin-2 (IL-2), which, if undertaken under the appropriate regulatory conditions and with approvals in place, would theoretically be amenable to clinical trial applications.

Key words

  • Fowlpox virus
  • Viral vaccine vectors
  • Co-expression
  • Tumor-associated antigens
  • Cytokines

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Acknowledgment

J.D.H. is in receipt of research funding support from Sementis Ltd. P.M.H. is the Chief Scientific Officer, co-founder, and a major shareholder of Sementis Ltd. K.R.D. is supported by a training fellowship and grant from the National Health and Medical Research Council of Australia.

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Howley, P.M., Diener, K.R., Hayball, J.D. (2014). Making an Avipoxvirus Encoding a Tumor-Associated Antigen and a Costimulatory Molecule. In: Lawman, M., Lawman, P. (eds) Cancer Vaccines. Methods in Molecular Biology, vol 1139. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0345-0_32

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  • DOI: https://doi.org/10.1007/978-1-4939-0345-0_32

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  • Publisher Name: Humana Press, New York, NY

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