Development of an Ad5H3 Chimera Using the "Antigen Capsid-Incorporation" Strategy for an Alternative Vaccination Approach.
Development of an Ad5H3 Chimera Using the "Antigen Capsid-Incorporation" Strategy for an Alternative Vaccination Approach.
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DOI：
10.2174/1874357901610010010
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Matthews QL
中科院分区：
文献类型：
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作者：
Gu L;Icyuz M;Krendelchtchikova V;Krendelchtchikov A;Johnston AE;Matthews QL
Adenovirus type 5 (Ad5) achieved success as a conventional transgene vaccine vector in preclinical trials, however; achieved poor efficiency in some of the clinical trials, due to the major hurdle associated with Ad5 pre-existing immunity (PEI) in the majority of the human population. We sought to generate Ad5-based chimeras to assess their capabilities to bypass this bottleneck and to induce antigen-specific humoral immune response. A His6 tag was incorporated into the hypervariable region 2 (HVR2) of hexon3 (H3) capsid protein using the “Antigen Capsid-Incorporation” strategy. This lead to the construction of a viral chimera, Ad5H3-HVR2-His. Ad5H3 was generated previously by substituting the hexon of Ad5 (hexon5) with the hexon from adenovirus type 3 (Ad3). His6 was presented on the viral capsid surface and recognized by a His6 antibody. An in vitro neutralization assay with Ad5 sera indicated the ability of Ad5 chimeras to partially escape Ad5 immunity. Immunization with Ad5H3-HVR2-His generated significant humoral response to the incorporated tagged peptide, when compared to the immunizations with controls. Based on our in vitro studies the data suggested that Ad5H3 as a novel chimeric vaccine platform yields the possibility to escape Ad5 neutralization, and the potential to generate robust humoral immunity against incorporated antigens using the “Antigen Capsid-Incorporation” strategy.
