Functionally inactivated dominant viral antigens of human cytomegalovirus delivered in replication incompetent adenovirus type 6 vectors as vaccine candidates
| Autor: | Aimin Tang, Daniel C. Freed, Fengsheng Li, Steve Meschino, Michael Prokop, Andrew Bett, Danilo Casimiro, Dai Wang, Tong-Ming Fu |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Human Vaccines & Immunotherapeutics, Vol 13, Iss 12, Pp 2763-2771 (2017) |
| Druh dokumentu: | article |
| ISSN: | 2164-5515 2164-554X 21645515 |
| DOI: | 10.1080/21645515.2017.1308988 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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