Abstract
Since CD8+ T cells have immunological memory and can eliminate tumor or infected cells, antigen-specific CD8+ T cell inducing DNA vaccines are potential next-generation vaccines. However, the relationship between single amino acid deletion of target antigens in plasmid DNA vaccines and vaccine efficacy is not completely understood. To address this knowledge disparity and improve DNA vaccine development, two constructs cytosolic form of ovalbumin, pOVAv (346 amino acids) and pOVAy (345 amino acids) were constructed and compared. OVA proteins from both constructs were detected in an in vitro experiment. Then, the efficacy of prophylactic DNA vaccination using a gene gun against OVA-expressing mouse thymoma cells was compared. Both constructs conferred protection against tumor challenge, and there was no significant difference between the efficacies of pOVAv and pOVAy. The pOVAv vaccine induced stronger antigen-specific cytotoxicity in vivo, while bone marrow-derived dendritic cells (BMDCs) transfected with pOVAv induced higher levels of IFN-γ production from OT-I CD8+ T cells in vitro compared to pOVAy. These results indicate that a single amino acid deletion at N-terminus of the target antigen in a DNA vaccine leads to a different immunological outcome. The small modification of the target antigen in the DNA vaccine might improve its efficacy against tumor or infectious diseases.
Highlights
Several types of vaccines, including live vaccines, attenuated vaccines, subunit vaccines, and DNA vaccines, are used to induce antigen-specific antibody production or T-cell responses [1]
We previously reported that ubiquitin molecules fused with target proteins in pcDNA3.1 vector efficiently induce an antigen-specific killer CD8+ T cell response and potentiate DNA vaccines against tumors and infectious diseases [14,15,16,17]
OVA band in the pcDNA-transfected cells was not detected. These results demonstrate that the degradation of the OVA protein is dependent on the proteasome, which is important for MHC class I epitope production
Summary
Several types of vaccines, including live vaccines, attenuated vaccines, subunit vaccines, and DNA vaccines, are used to induce antigen-specific antibody production or T-cell responses [1]. DNA is more stable than proteins used for subunit vaccines, so it can be stored at room temperature and does not require refrigeration. Some groups in the USA have been testing a DNA vaccine by Biojector® , VRC-HIVDNA016-00-VP, and have succeeded in potentiating an antibody and CD8+ T cell response against HIV [3,4]. DNA vaccines against animal diseases, including West Nile virus of condors and horses “West Nile Innovator® DNA” (Fort Dodge Animal Health/Pfizer, New York, NY, USA), infectious hematopoietic necrosis of salmonids“Apex-IHN® ” (Aqua Health Ltd., an affiliate of Novartis Animal Health Inc., Wrentham, MA, USA), and canine melanoma “Oncept” (Merial, Lyon, France), are already commercially available [5,6,7,8]
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