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In particular, the chimpanzee Ad vector, ChAdOx1, has taken centre stage as a leading COVID-19 vaccine candidate. However, despite mounting data, both clinical and pre-clinical, demonstrating effective induction of adaptive immune responses, the innate immune signals that precede the protective responses that make these vectors attractive vaccine platforms remain poorly understood.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In this study, a mouse immunisation model was used to evaluate whole blood gene expression changes 24\u2009h after either a single dose or heterologous prime-boost regimen of an Ad and\/or MVA vaccine. We demonstrate through comparative analysis of Ad vectors encoding different antigens that a transgene product-specific gene signature can be discerned from the vector-induced transcriptional response. Expression of genes involved in TLR2 stimulation and \u03b3\u03b4 T cell and natural killer cell activation were induced after a single dose of Ad, while MVA led to greater expression of type I interferon genes. The order of prime-boost combinations was found to influence the magnitude of the gene expression changes, with MVA\/Ad eliciting greater transcriptional perturbation than Ad\/MVA. Contrasting the two regimens revealed significant enrichment of epigenetic regulation pathways and augmented expression of MHC class I and II molecules associated with MVA\/Ad.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>These data demonstrate that the order in which vaccines from heterologous prime-boost regimens are administered leads to distinct transcriptional responses and may shape the immune response induced by such combinations. The characterisation of early vaccine-induce responses strengthens our understanding of viral vector vaccine mechanisms of action ahead of their characterisation in human clinical trials and are a valuable resource to inform the pre-clinical design of appropriate vaccine constructs for emerging infectious diseases.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12864-021-08061-8","type":"journal-article","created":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T12:02:41Z","timestamp":1635595361000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Distinct patterns of whole blood transcriptional responses are induced in mice following immunisation with adenoviral and poxviral vector vaccines encoding the same antigen"],"prefix":"10.1186","volume":"22","author":[{"given":"Dylan","family":"Sheerin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Dold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"O\u2019Connor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Pollard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine S.","family":"Rollier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,30]]},"reference":[{"key":"8061_CR1","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1128\/IAI.00740-09","volume":"78","author":"A Reyes-Sandoval","year":"2010","unstructured":"Reyes-Sandoval A, et al. 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Procedures were approved by the University of Oxford Animal Care and Ethical Review Committee. The study was carried out in compliance with the ARRIVE guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"A.J.P. is Chair of UK Dept. Health and Social Care\u201fs (DHSC) Joint Committee on Vaccination & Immunisation (JCVI), and is a member of the WHO\u201fs SAGE. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, NIHR or WHO. The University of Oxford has entered into a partnership with AstraZeneca on coronavirus vaccine development. C.S.R., C.D., D.S., and A.J.P. are named inventors on a patent application in the field of meningococcal vaccine. A.J.P waives all his rights to any patent. D.O\u201fC. has no competing interests to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"777"}}