Cargando…
Development of an Ad5H3 Chimera Using the “Antigen Capsid-Incorporation” Strategy for an Alternative Vaccination Approach
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. OB...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Bentham Open
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892130/ https://www.ncbi.nlm.nih.gov/pubmed/27335626 http://dx.doi.org/10.2174/1874357901610010010 |
_version_ | 1782435367293550592 |
---|---|
author | Gu, Linlin Icyuz, Mert Krendelchtchikova, Valentina Krendelchtchikov, Alexandre Johnston, Alison E. Matthews, Qiana L. |
author_facet | Gu, Linlin Icyuz, Mert Krendelchtchikova, Valentina Krendelchtchikov, Alexandre Johnston, Alison E. Matthews, Qiana L. |
author_sort | Gu, Linlin |
collection | PubMed |
description | 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 His(6) 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: His(6) was presented on the viral capsid surface and recognized by a His(6) 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. |
format | Online Article Text |
id | pubmed-4892130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Bentham Open |
record_format | MEDLINE/PubMed |
spelling | pubmed-48921302016-06-22 Development of an Ad5H3 Chimera Using the “Antigen Capsid-Incorporation” Strategy for an Alternative Vaccination Approach Gu, Linlin Icyuz, Mert Krendelchtchikova, Valentina Krendelchtchikov, Alexandre Johnston, Alison E. Matthews, Qiana L. Open Virol J Article 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 His(6) 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: His(6) was presented on the viral capsid surface and recognized by a His(6) 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. Bentham Open 2016-04-26 /pmc/articles/PMC4892130/ /pubmed/27335626 http://dx.doi.org/10.2174/1874357901610010010 Text en © Gu et al.; Licensee Bentham Open. https://creativecommons.org/licenses/by/4.0/legalcode This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited. |
spellingShingle | Article Gu, Linlin Icyuz, Mert Krendelchtchikova, Valentina Krendelchtchikov, Alexandre Johnston, Alison E. Matthews, Qiana L. Development of an Ad5H3 Chimera Using the “Antigen Capsid-Incorporation” Strategy for an Alternative Vaccination Approach |
title | Development of an Ad5H3 Chimera Using the “Antigen Capsid-Incorporation” Strategy for an Alternative Vaccination Approach |
title_full | Development of an Ad5H3 Chimera Using the “Antigen Capsid-Incorporation” Strategy for an Alternative Vaccination Approach |
title_fullStr | Development of an Ad5H3 Chimera Using the “Antigen Capsid-Incorporation” Strategy for an Alternative Vaccination Approach |
title_full_unstemmed | Development of an Ad5H3 Chimera Using the “Antigen Capsid-Incorporation” Strategy for an Alternative Vaccination Approach |
title_short | Development of an Ad5H3 Chimera Using the “Antigen Capsid-Incorporation” Strategy for an Alternative Vaccination Approach |
title_sort | development of an ad5h3 chimera using the “antigen capsid-incorporation” strategy for an alternative vaccination approach |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892130/ https://www.ncbi.nlm.nih.gov/pubmed/27335626 http://dx.doi.org/10.2174/1874357901610010010 |
work_keys_str_mv | AT gulinlin developmentofanad5h3chimerausingtheantigencapsidincorporationstrategyforanalternativevaccinationapproach AT icyuzmert developmentofanad5h3chimerausingtheantigencapsidincorporationstrategyforanalternativevaccinationapproach AT krendelchtchikovavalentina developmentofanad5h3chimerausingtheantigencapsidincorporationstrategyforanalternativevaccinationapproach AT krendelchtchikovalexandre developmentofanad5h3chimerausingtheantigencapsidincorporationstrategyforanalternativevaccinationapproach AT johnstonalisone developmentofanad5h3chimerausingtheantigencapsidincorporationstrategyforanalternativevaccinationapproach AT matthewsqianal developmentofanad5h3chimerausingtheantigencapsidincorporationstrategyforanalternativevaccinationapproach |