{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:05:57Z","timestamp":1772118357584,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T00:00:00Z","timestamp":1559088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["109965MA"],"award-info":[{"award-number":["109965MA"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004664","name":"British Infection Association","doi-asserted-by":"publisher","award":["\/ 099897\/Z\/12\/A"],"award-info":[{"award-number":["\/ 099897\/Z\/12\/A"]}],"id":[{"id":"10.13039\/501100004664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Adenoviral vectors induce robust epitope\u2010specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses. Within the repertoire of responses generated both conventional memory evolution and the phenomenon of memory inflation are seen. The rules governing which epitopes inflate are not fully known, but may include a role for both antigen processing and competition. To investigate this, we looked at memory generated from vectors targeting the Gp33\u201041 (KAVYNFATC\/K9C) epitope from the gp of lymphocytic choriomeningitis virus (LCMV) in mice. This well\u2010described epitope has both the Gp33\u201041 and Gp34\u201041 epitopes embedded within it. Vaccination with a full\u2010length gp or a minigene Ad\u2010Gp33\/K9C vector\u2010induced conventional memory responses against the immunodominant Gp33\/K9C epitope but a strong inflationary response against the Gp34\/A8C epitope. These responses showed sustained in vivo function, with complete protection against LCMV infectious challenge. Given the unexpected competition between epitopes seen in the minigene model, we further tested epitope competition using the full\u2010length Ad\u2010LacZ (\u03b2\u2010galactosidase) model. Generation of an Ad\u2010LacZ vector with a single amino acid disruption of the inflationary \u03b2\u2010gal\n                    <jats:sub>96\u2010103<\/jats:sub>\n                    \/D8V epitope transformed the \u03b2\u2010gal\n                    <jats:sub>497\u2010504<\/jats:sub>\n                    \/I8V epitope from conventional to inflationary memory. This work collectively demonstrates the importance of epitope competition within adenoviral vector inserts and is of relevance to future studies using adenoviral vectored immunogens.\n                  <\/jats:p>","DOI":"10.1002\/eji.201948143","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T04:32:37Z","timestamp":1558326757000},"page":"1356-1363","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Divergent memory responses driven by adenoviral vectors are impacted by epitope competition"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3337-2455","authenticated-orcid":false,"given":"Julia M","family":"Colston","sequence":"first","affiliation":[{"name":"Nuffield Department of Medicine Peter Medawar Building for Pathogen Research, University of Oxford  Oxford UK"},{"name":"Institute of Immunobiology Kantonsspital St. Gallen  St. Gallen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Hutchings","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine Peter Medawar Building for Pathogen Research, University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Senthil","family":"Chinnakannan","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine Peter Medawar Building for Pathogen Research, University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Highton","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine Peter Medawar Building for Pathogen Research, University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Perez\u2010Shibayama","sequence":"additional","affiliation":[{"name":"Institute of Immunobiology Kantonsspital St. Gallen  St. Gallen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burkhard","family":"Ludewig","sequence":"additional","affiliation":[{"name":"Institute of Immunobiology Kantonsspital St. Gallen  St. Gallen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Klenerman","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine Peter Medawar Building for Pathogen Research, University of Oxford  Oxford 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