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As many other pathogens, these oncogenic <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>s belong to an ancient and diverse virus family. Therefore, we found it relevant to investigate the potential and limitations of inducing a broad response\u2014either by inducing cross\u2010reactive T cells or by administering a polyvalent vaccine. To test these strategies, we designed three ancestral and two circulating sequences based on the two domains of the E1 and E2 proteins of papillomaviruses (<jats:styled-content style=\"fixed-case\">PV<\/jats:styled-content>s) that exhibit the highest degree of conservation in comparison with the other <jats:styled-content style=\"fixed-case\">PV<\/jats:styled-content> proteins. The <jats:styled-content style=\"fixed-case\">PV<\/jats:styled-content> sequences were fused to a T cell adjuvant, the murine invariant chain and encoded in a recombinant adenoviral vector which was administered to na\u00efve outbred mice. By measuring T cell responses induced by these different vaccines and towards peptide pools representing three circulating strains and a putative ancestor of oncogenic <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content>s, we showed that the ancestral vaccine antigen has to be approximately 90% identical to the circulating <jats:styled-content style=\"fixed-case\">PV<\/jats:styled-content>s before a marked drop of ~90% mean <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8+ T cell responses ensues. Interestingly, the combination of two or three type\u2010specific <jats:styled-content style=\"fixed-case\">PV<\/jats:styled-content> vaccines did not induce a significant decrease in the <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8+ T cell response to the individual\u2010targeted <jats:styled-content style=\"fixed-case\">PV<\/jats:styled-content> types. Polyvalent <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> vaccine based on the E1 and E2 proteins seem to be capable of triggering responses towards more than one type of <jats:styled-content style=\"fixed-case\">PV<\/jats:styled-content> while the cross\u2010reactivity of ancestral vaccine seems insufficient in consideration of the sequence diversity between <jats:styled-content style=\"fixed-case\">HPV<\/jats:styled-content> types.<\/jats:p>","DOI":"10.1111\/sji.12522","type":"journal-article","created":{"date-parts":[[2017,1,21]],"date-time":"2017-01-21T07:02:42Z","timestamp":1484982162000},"page":"182-190","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Breadth of T Cell Responses After Immunization with Adenovirus Vectors Encoding Ancestral Antigens or Polyvalent Papillomavirus Antigens"],"prefix":"10.1111","volume":"85","author":[{"given":"E.","family":"Ragonnaud","sequence":"first","affiliation":[{"name":"Department of International Health Immunology and Microbiology Center for Medical Parasitology Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. 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