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Studies with mice indicated that vectors based on AAV type 7 (AAV7), AAV8, and AAV9 demonstrate improved immunogenicity in terms of Gag CD8<jats:sup>+<\/jats:sup>T-cell and Gag antibody responses. The quality of these antigen-specific responses was evaluated in detail for AAV2\/8 vectors and compared to results with an adenovirus vector expressing Gag (AdC7). AAV2\/8 produced a vibrant CD8<jats:sup>+<\/jats:sup>T-cell effector response characterized by coexpression of gamma interferon and tumor necrosis factor alpha as well as in vivo cytolytic activity. No CD8<jats:sup>+<\/jats:sup>T-cell response generated by any of the AAVs was effectively boosted with AdC7, a result consistent with the finding of a relative lack of cells expressing interleukin-2 (IL-2) or a central memory phenotype at 3 months after the prime. The primary response to an AdC7 vaccine differed from that generated by AAVs in that the peak effector response evolved into populations of Gag-specific T cells expressing high levels of cytokines, including IL-2, and with effector memory and central memory phenotypes. A number of mechanisms could be considered to explain the aberrant activation of CD8<jats:sup>+<\/jats:sup>T cells by AAV, including insufficient inflammatory responses, CD4 help, and\/or chronic antigen expression and T-cell exhaustion. Interestingly, the B-cell response to AAV-encoded Gag was quite vibrant and easily boosted with AdC7.<\/jats:p>","DOI":"10.1128\/jvi.01253-07","type":"journal-article","created":{"date-parts":[[2007,8,23]],"date-time":"2007-08-23T00:43:54Z","timestamp":1187829834000},"page":"11840-11849","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":59,"title":["Vaccines Based on Novel Adeno-Associated Virus Vectors Elicit Aberrant CD8<sup>+<\/sup>T-Cell Responses in Mice"],"prefix":"10.1128","volume":"81","author":[{"given":"Jianping","family":"Lin","sequence":"first","affiliation":[{"name":"Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 125 S. 31st Street, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhi","sequence":"additional","affiliation":[{"name":"Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 125 S. 31st Street, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Mays","sequence":"additional","affiliation":[{"name":"Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 125 S. 31st Street, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 125 S. 31st Street, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","first-page":"754","volume":"9","year":"1965","unstructured":"Atchison, R. 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