Development of an Ad5H3 Chimera Using the “Antigen Capsid-Incorporation” Strategy for an Alternative Vaccination Approach



Linlin Gu1, Mert Icyuz2, Valentina Krendelchtchikova1, Alexandre Krendelchtchikov1, Alison E. Johnston3, Qiana L. Matthews1, 4, *
1 Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, 845 19th street south, Birmingham, AL,35294, USA
2 Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA
3 Division of Natural Sciences and Math, Miles College, Fairfield, AL, 35064, USA
4 Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL, 35294, USA


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© Gu et al.; Licensee Bentham Open.

open-access license: 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.

Correspondence: * Address correspondence to this author at the Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Tel: (205)-934-0573; Fax: (205) 934-5600; E-mail: qlm@uab.edu


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.

Keywords: Adenovirus type 3 (Ad3), Adenovirus type 5 (Ad5), Ad5 pre-existing immunity (PEI), Antigen Capsid-Incorporation strategy, Chimeric Ad5H3, Humoral immunity.