Linlin Gu, Mert Icyuz, Valentina Krendelchtchikova, Alexandre Krendelchtchikov, Alison E Johnston, Qiana L Matthews
{"title":"Development of an Ad5H3 Chimera Using the \"Antigen Capsid-Incorporation\" Strategy for an Alternative Vaccination Approach.","authors":"Linlin Gu, Mert Icyuz, Valentina Krendelchtchikova, Alexandre Krendelchtchikov, Alison E Johnston, Qiana L Matthews","doi":"10.2174/1874357901610010010","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>We sought to generate Ad5-based chimeras to assess their capabilities to bypass this bottleneck and to induce antigen-specific humoral immune response.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"10 ","pages":"10-20"},"PeriodicalIF":0.0000,"publicationDate":"2016-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1f/3b/TOVJ-10-10.PMC4892130.pdf","citationCount":"8","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Open Virology Journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/1874357901610010010","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2016/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 8
Abstract
Background: 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.
Objective: We sought to generate Ad5-based chimeras to assess their capabilities to bypass this bottleneck and to induce antigen-specific humoral immune response.
Methods: 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).
Results: 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.
Conclusion: 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.