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Abstract
Gene expression profiling of the blood cell response induced early after vaccination has previously been demonstrated to predict the immunogenicity of vaccines. In this study, we evaluated whether the analysis of the gene expression profile of skin-migrated dendritic cells (DCs) could be informative for the in vitro prediction of immunogenicity of vaccine, using canine adenovirus serotype 2 (CAV2) as vaccine vector. CAV2 has been shown to induce immunity to transgenes in several species including sheep and is an interesting alternative to human adenovirus-based vectors, based on the safety records of the parental strain in dogs and the lack of pre-existing immunity in non-host species. Skin-migrated DCs were collected from pseudo-afferent lymph in sheep. Both the CD11b+ -type and CD103+ -type skin-migrated DCs were transduced by CAV2. An analysis of the global gene response to CAV2 in the two skin DC subsets showed that the gene response in CD11b+ -type DCs was far higher and broader than in the CD103+ -type DCs. A newly released integrative analytic tool from Ingenuity systems revealed that the CAV2-modulated genes in the CD11b+ -type DCs clustered in several activated immunogenicity-related functions, such as immune response, immune cell trafficking and inflammation. Thus gene profiling in skin-migrated DC in vitro indicates that the CD11b+ DC type is more responsive to CAV2 than the CD103+ DC type, and provides valuable information to help in evaluating and possibly improving viral vector vaccine effectiveness.
Highlights
Gene expression profiling of the in vivo innate immune response to vaccines in peripheral blood mononuclear cells (PBMCs) has recently been demonstrated to be predictive of the subsequent magnitude of the antibody and CD8+ T cell responses in humans [1,2]
We found that canine adenovirus serotype 2 (CAV2) transduced both the CD11b+ and the CD103+ -type dendritic cells (DCs) in vitro, with a slightly higher efficiency in the later, but only the CD11b+-type DC subset presented a broad pattern of gene responses to CAV2 that is associated to dendritic cell maturation, communication between innate and adaptive immune cells, immune cell trafficking, and immune response
We evaluated whether CAV2 can transduce the skin-migrated sheep DC subsets collected from afferent lymph
Summary
Gene expression profiling of the in vivo innate immune response to vaccines in peripheral blood mononuclear cells (PBMCs) has recently been demonstrated to be predictive of the subsequent magnitude of the antibody and CD8+ T cell responses in humans [1,2]. In support of this proposal, a recent study showed that the gene expression profile of bone marrow-derived sheep DCs in response to recombinant myxoma virus vectors included many genes that were previously shown to predict vaccine efficacy [3]. Skin-migrated DCs collected from pseudo-afferent lymph include two major subsets, the CD26+ SIRP2 and CD262 SIRP+ DCs that were shown to be homologous to the mouse CD8+a/CD103+ DC and CD11b+ DC types respectively, based on transcriptomic and functional assays [9]. The CD26+ SIRP2 DC subset is specialized in CD8+ T cell activation in mixed leukocyte reactions and in soluble antigen cross-presentation [9]
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