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.
Highlights
Adenovirus type 5 (Ad5) has been the most studied virus for vectored therapies, due to the vector’s advantages in genetic modification and host applicability [1]
A His6 tag was incorporated into the hypervariable region 2 (HVR2) of hexon3 (H3) capsid protein using the “Antigen CapsidIncorporation” strategy
An in vitro neutralization assay with Ad5 sera indicated the ability of Ad5 chimeras to partially escape Ad5 immunity
Summary
Adenovirus type 5 (Ad5) has been the most studied virus for vectored therapies, due to the vector’s advantages in genetic modification and host applicability [1]. Ad5’s major disadvantage is its pre-existing immunity (PEI) in the majority of the human population This disadvantage could decrease the efficacy of Ad5-vectored clinical therapies [2]. Most recombinant Ad5 vectors are based on the traditional transgene method, which replaces the Ad5 early genes (E) with foreign genes of interest. These types of vectors are neutralized by Ad5 NAbs. Adenovirus type 5 (Ad5) achieved success as a conventional transgene vaccine vector in preclinical trials, ; 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
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