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We found that single\u2010clade A, B and C vaccines applied alone induced only limited cross\u2010clade reactivity and that the epitope hierarchy varied according to the immunizing clade. However, combining single\u2010clade HIV\u20101 vaccines into multi\u2010clade formulations resulted in multiple forms of <jats:italic>in vivo<\/jats:italic> immune interference such as original antigenic sin and antagonism, which dampened or even abrogated induction of responses to epitope variants and reduced the breadth of induced T cell responses. Simultaneous administration of individual clade\u2010specific vaccines into anatomically separated sites on the body alleviated antagonism and increased the number of detectable epitope responses. Although cross\u2010reactivity of murine CD8<jats:sup>+<\/jats:sup> T cells does not directly translate to humans, the molecular interactions involved in triggering T cell responses are the same in mouse and man. Thus, these results have important ramifications for the design of both prophylactic and therapeutic vaccines against HIV\u20101 and other highly variable pathogens.<\/jats:p>","DOI":"10.1002\/eji.200636711","type":"journal-article","created":{"date-parts":[[2007,1,17]],"date-time":"2007-01-17T15:48:49Z","timestamp":1169048929000},"page":"566-577","source":"Crossref","is-referenced-by-count":28,"title":["Combined single\u2010clade candidate HIV\u20101 vaccines induce T cell responses limited by multiple forms of <i>in vivo<\/i> immune interference"],"prefix":"10.1002","volume":"37","author":[{"given":"Natasha","family":"Larke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eung\u2010Jun","family":"Im","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn","family":"Williamson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna\u2010Lise","family":"Williamson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew\u2004J.","family":"McMichael","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom\u00e1\u0161","family":"Hanke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,2]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/bmb\/58.1.19"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.01.026"},{"key":"e_1_2_7_3_2","doi-asserted-by":"crossref","first-page":"8908","DOI":"10.1128\/jvi.71.11.8908-8911.1997","article-title":"Cross\u2010clade human immunodeficiency virus (HIV)\u2010specific cytotoxic T\u2010lymphocyte responses in HIV\u2010infected Zambians.","volume":"71","author":"Betts M. 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