Functionally inactivated dominant viral antigens of human cytomegalovirus delivered in replication incompetent adenovirus type 6 vectors as vaccine candidates
| Autor: | Dai Wang, Andrew J. Bett, Michael Prokop, Danilo R. Casimiro, Daniel C. Freed, Tong-Ming Fu, Aimin Tang, Fengsheng Li, Steve Meschino |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Human cytomegalovirus Primates viruses Immunology Genetic Vectors Cytomegalovirus non-human primate Biology Immediate early protein Viral vector Immediate-Early Proteins Viral Matrix Proteins 03 medical and health sciences Transactivation Cytomegalovirus Vaccines Mastadenovirus 0302 clinical medicine Antigen vaccine medicine Immunology and Allergy Animals Antigens Viral Viral antigens Pharmacology Drug Carriers Mice Inbred BALB C Vaccines Synthetic T cell immunity Immunogenicity adenovirus vector virus diseases Defective Viruses medicine.disease Phosphoproteins Virology Research Papers Mice Inbred C57BL 030104 developmental biology cytomegalovirus (CMV) Trans-Activators Female Mutant Proteins Nuclear localization sequence 030215 immunology |
| Zdroj: | Human Vaccines & Immunotherapeutics |
| ISSN: | 2164-554X 2164-5515 |
| 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: | OpenAIRE |
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