title: The relative magnitude of transgene-specific adaptive immune responses induced by human and chimpanzee adenovirus vectors differs between laboratory animals and a target species.
abstract: Adenovirus vaccine vectors generated from new viral serotypes are routinely screened in pre-clinical laboratory animal models to identify the most immunogenic and efficacious candidates for further evaluation in clinical human and veterinary settings. Here, we show that studies in a laboratory species do not necessarily predict the hierarchy of vector performance in other mammals. In mice, after intramuscular immunization, HAdV-5 (Human adenovirus C) based vectors elicited cellular and humoral adaptive responses of higher magnitudes compared to the chimpanzee adenovirus vectors ChAdOx1 and AdC68 from species Human adenovirus E. After HAdV-5 vaccination, transgene specific IFN-γ(+) CD8(+) T cell responses reached peak magnitude later than after ChAdOx1 and AdC68 vaccination, and exhibited a slower contraction to a memory phenotype. In cattle, cellular and humoral immune responses were at least equivalent, if not higher, in magnitude after ChAdOx1 vaccination compared to HAdV-5. Though we have not tested protective efficacy in a disease model, these findings have important implications for the selection of candidate vectors for further evaluation. We propose that vaccines based on ChAdOx1 or other Human adenovirus E serotypes could be at least as immunogenic as current licensed bovine vaccines based on HAdV-5.
authors: The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK. Electronic address: matthew.dicks@kcl.ac.uk.
authors: Matthew D J
authors: MD
authors: Dicks
authors: The Pirbright Institute, Pirbright Laboratory, Pirbright, Surrey GU24 0NF, UK.
authors: Efrain
authors: E
authors: Guzman
authors: The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors: Alexandra J
authors: AJ
authors: Spencer
authors: The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors: Sarah C
authors: SC
authors: Gilbert
authors: The Pirbright Institute, Pirbright Laboratory, Pirbright, Surrey GU24 0NF, UK.
authors: Bryan
authors: B
authors: Charleston
authors: The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors: Adrian V S
authors: AV
authors: Hill
authors: The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, UK.
authors: Matthew G
authors: MG
authors: Cottingham
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000830:Animals, Laboratory; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002417:Cattle; D004337:Drug Carriers; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D019076:Transgenes; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D004337:Drug Carriers; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D007371:Interferon-gamma
keywords: Vaccine immunology; Viral vector
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