{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:42:39Z","timestamp":1792680159711,"version":"4.5.0"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"20","license":[{"start":{"date-parts":[[2017,10,15]],"date-time":"2017-10-15T00:00:00Z","timestamp":1508025600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BA 4432\/1-1"],"award-info":[{"award-number":["BA 4432\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RTG 1949\/1"],"award-info":[{"award-number":["RTG 1949\/1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2017,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Adenovirus (Ad)-based immunization is a popular approach in vaccine development, and Ad-based vectors are renowned for their potential to induce strong CD8\n            <jats:sup>+<\/jats:sup>\n            T cell responses to the encoded transgene. Surprisingly, we previously found in the mouse Friend retrovirus (FV) model that Ad-based immunization did not induce CD8\n            <jats:sup>+<\/jats:sup>\n            T cell responses to the FV Leader-Gag-derived immunodominant epitope GagL\n            <jats:sub>85\u201393<\/jats:sub>\n            . We show now that induction of GagL\n            <jats:sub>85\u201393<\/jats:sub>\n            -specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cells was highly effective when leader-Gag was delivered by plasmid DNA immunization, implying a role for Ad-derived epitopes in mediating unresponsiveness. By immunizing with DNA constructs encoding strings of GagL\n            <jats:sub>85\u201393<\/jats:sub>\n            and the two Ad-derived epitopes DNA-binding protein\n            <jats:sub>418\u2013426<\/jats:sub>\n            (DBP\n            <jats:sub>418\u2013426<\/jats:sub>\n            ) and hexon\n            <jats:sub>486\u2013494<\/jats:sub>\n            , we confirmed that Ad epitopes prevent induction of GagL\n            <jats:sub>85\u201393<\/jats:sub>\n            -specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cells. Interestingly, while DBP\n            <jats:sub>418\u2013426<\/jats:sub>\n            did not interfere with GagL\n            <jats:sub>85\u201393<\/jats:sub>\n            -specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cell induction, the H-2D\n            <jats:sup>d<\/jats:sup>\n            -restricted hexon\n            <jats:sub>486\u2013494<\/jats:sub>\n            suppressed the CD8\n            <jats:sup>+<\/jats:sup>\n            T cell response to the H-2D\n            <jats:sup>b<\/jats:sup>\n            -restricted GagL\n            <jats:sub>85\u201393<\/jats:sub>\n            strongly in H-2\n            <jats:sup>b\/d<\/jats:sup>\n            mice but not in H-2\n            <jats:sup>b\/b<\/jats:sup>\n            mice. This finding indicates that competition occurs at the level of responding CD8\n            <jats:sup>+<\/jats:sup>\n            T cells, and we could indeed demonstrate that coimmunization with an interleukin 2 (IL-2)-encoding plasmid restored GagL\n            <jats:sub>85\u201393<\/jats:sub>\n            -specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cell responses to epitope strings in the presence of hexon\n            <jats:sub>486\u2013494<\/jats:sub>\n            . IL-2 codelivery did not restore GagL\n            <jats:sub>85\u201393<\/jats:sub>\n            responsiveness in Ad-based immunization, however, likely due to the presence of further epitopes in the Ad vector. Our findings show that seemingly immunodominant transgene epitopes can be dominated by Ad-derived epitopes. These findings underline the importance of thorough characterization of vaccine vectors, and modifications of vectors or immunogens may be required to prevent impaired transgene-specific immune responses.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Ad-based vectors are widely used in experimental preclinical and clinical immunization studies against numerous infectious agents, such as human immunodeficiency virus, Ebola virus,\n            <jats:named-content content-type=\"genus-species\">Plasmodium falciparum<\/jats:named-content>\n            , or\n            <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n            . Preexisting immunity to Ad-based vectors is widely recognized as a hindrance to the widespread use of Ad-based vectors for immunizations in humans; however, our data show that an immune response to Ad-derived T cell epitopes can also result in loss or impairment of transgene-specific immune responses in prenaive vaccinees due to immune competition. Our results highlight that seemingly immunodominant epitopes may be affected by dominance of vector-derived epitopes, and modifications of the vector design or the immunogens employed in immunization may lead to more effective vaccines.\n          <\/jats:p>","DOI":"10.1128\/jvi.01184-17","type":"journal-article","created":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T00:30:33Z","timestamp":1501720233000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Immunodominance of Adenovirus-Derived CD8\n            <sup>+<\/sup>\n            T Cell Epitopes Interferes with the Induction of Transgene-Specific Immunity in Adenovirus-Based Immunization"],"prefix":"10.1128","volume":"91","author":[{"given":"Dominik","family":"Sch\u00f6ne","sequence":"first","affiliation":[{"name":"Institute for Virology, University Hospital Essen, University Duisburg-Essen, Essen, 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