Noncarrier naked antigen-specific DNA vaccine generates potent antigen-specific immunologic responses and antitumor effects
Journal
Gene Therapy
Journal Volume
16
Journal Issue
6
Pages
776-787
Date Issued
2009
Author(s)
Chang M.-C.
Chen S.M.
Abstract
Genetic immunization strategies have largely focused on the use of plasmid DNA with a gene gun. However, there remains a clear need to further improve the efficiency, safety, and cost of potential DNA vaccines. The gold particle-coated DNA format delivered through a gene gun is expensive, time and process consuming, and raises aseptic safety concerns. This study aims to determine whether a low-pressured gene gun can deliver noncarrier naked DNA vaccine without any particle coating, and generate similarly strong antigen-specific immunologic responses and potent antitumor effects compared with gold particle-coated DNA vaccine. Our results show that mice vaccinated with noncarrier naked chimeric CRT/E7 DNA lead to dramatic increases in the numbers of E7-specific CD8+ T-cell precursors and markedly raised titers of E7-specific antibodies. Furthermore, noncarrier naked CRT/E7 DNA vaccine generated potent antitumor effects against subcutaneous E7-expressing tumors and pre-established E7-expressing metastatic pulmonary tumors. In addition, mice immunized with noncarrier naked CRT/E7 DNA vaccine had significantly less burning effects on the skin compared with those vaccinated with gold particle-coated CRT/E7 DNA vaccine. We conclude that noncarrier naked CRT/E7 DNA vaccine delivered with a low-pressured gene gun can generate similarly potent immunologic responses and effective antitumor effects has fewer side effects, and is more convenient than conventional gold particle-coated DNA vaccine.
SDGs
Other Subjects
calreticulin; calreticulin protein E7 DNA vaccine; DNA vaccine; gold nanoparticle; naked DNA; protein E7; unclassified drug; animal cell; animal experiment; animal model; animal tissue; antigen specificity; antineoplastic activity; article; cancer gene therapy; cancer immunotherapy; cancer prevention; CD8+ T lymphocyte; chimera; controlled study; DNA immunization; drug coating; drug dosage form comparison; drug megadose; female; gene gun; immune response; injection site burning; local skin reaction; lung metastasis; mouse; neoplasm; nonhuman; priority journal; prolymphocyte; skin defect; subcutaneous tissue tumor; vaccination reaction; Animals; Antigens, CD11c; Biolistics; Buffers; Burns, Chemical; Cancer Vaccines; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Cells, Cultured; Dendritic Cells; Dermis; Dose-Response Relationship, Immunologic; Drug Carriers; Enzyme-Linked Immunosorbent Assay; Epitopes, T-Lymphocyte; Female; Flow Cytometry; Gold; Immunotherapy; Injections, Intradermal; Luciferases; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Neoplasms; Neoplasms, Experimental; Papillomavirus E7 Proteins; Pressure; Recombinant Fusion Proteins; Vaccines, DNA; Mus
Type
journal article