Foreign gene expression and induction of antibody response by recombinant fowl adenovirus-9-based vectors with exogenous promoters.

Autor: Ackford JG; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada., Corredor JC; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada., Pei Y; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada., Krell PJ; Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada., Bédécarrats G; Department of Animal Biosciences, University of Guelph, Guelph, Ontario, Canada., Nagy É; Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada. Electronic address: enagy@uoguelph.ca.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2017 Sep 05; Vol. 35 (37), pp. 4974-4982. Date of Electronic Publication: 2017 Aug 02.
DOI: 10.1016/j.vaccine.2017.07.087
Abstrakt: Fowl adenoviruses (FAdVs) are promising vectors for poultry vaccines and gene therapy. The commonly used human cytomegalovirus (CMV) promoter in recombinant FAdV-9 viruses (recFAdV-9s) leads to foreign gene expression that elicits an antibody response. Despite its strength, studies have shown that the CMV promoter is prone to silencing by methylation hampering the in vivo application of vectors containing this promoter. Therefore, to improve our virus vector system and circumvent potential limitations of silencing, we engineered recFAdV-9s with foreign gene expression cassettes carrying the CMV enhancer/chicken β-actin (CAG) or the human elongation factor 1 alpha (EF1α) promoters with or without the posttranscriptional regulatory element of woodchuck hepatitis virus (WPRE). Chicken hepatoma cells (CH-SAH) infected with recFAdV-9s carrying either CAG or EF1α promoters expressed higher levels of foreign protein than those infected with recFAdV-9 carrying the CMV promoter. Incorporation of the WPRE element rendered lower gene expression regardless of promoter type. Surprisingly, most chickens inoculated with recFAdV-9 containing the CMV promoter had the highest antibody response to foreign protein compared to other promoters. Our findings suggest the importance of promoter selection for candidate virus vector vaccines based on humoral immune response rather than foreign protein expression levels in vitro.
(Copyright © 2017 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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