Functionally inactivated dominant viral antigens of human cytomegalovirus delivered in replication incompetent adenovirus type 6 vectors as vaccine candidates
T cell immunity is critical in controlling human cytomegalovirus (HCMV) infection in transplant recipients, and T cells targeting viral immediate early proteins such as IE1, IE2 and pp65 have been speculated to be more effective against reactivation. Here we report efforts to construct replication i...
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Published in | Human vaccines & immunotherapeutics Vol. 13; no. 12; pp. 2763 - 2771 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Taylor & Francis
02.12.2017
Taylor & Francis Group |
Subjects | |
Online Access | Get full text |
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Summary: | T cell immunity is critical in controlling human cytomegalovirus (HCMV) infection in transplant recipients, and T cells targeting viral immediate early proteins such as IE1, IE2 and pp65 have been speculated to be more effective against reactivation. Here we report efforts to construct replication incompetent adenovirus 6 vectors expressing these viral antigens as vaccine candidates. To reduce the potential liabilities of these viral proteins as vaccine antigens, we introduced mutations to inactivate their reported functions including their nuclear localization signals. The modifications greatly reduced their localization to the nuclei, thus limiting their interactions with cellular proteins important for cell cycle modulation and transactivation. The immunogenicity of modified pp65, IE1 and IE2 vaccines was comparable to their wild-type counterparts in mice and the immunogenicity of the modified antigens was demonstrated in non-human primates. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/khvi. Supplemental data for this article can be accessed on the publisher's website. Present address: Aeras, Rockville, MD, USA. |
ISSN: | 2164-5515 2164-554X |
DOI: | 10.1080/21645515.2017.1308988 |