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Enhancing DNA vaccine potency by co-administration of xenogenic MHC class-I DNA

Gene Therapy volume 17, pages 531–540 (2010)Cite this article

Abstract

Intramuscular administration of DNA vaccines can lead to the generation of antigen-specific immune responses through cross-priming mechanisms. We propose a strategy that is capable of leading to local inflammation and enhancing cross-priming, thus resulting in improved antigen-specific immune responses. Therefore, in this study, we evaluated the immunological responses elicited through electroporation-mediated intramuscular administration of a DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 E7 (CRT–E7) in combination with DNA expressing HLA-A2 as compared with CRT–E7 DNA vaccination alone. We found that the co-administration of a DNA vaccine in conjunction with a DNA encoding a xenogenic major histocompatibility complex (MHC) molecule could significantly enhance the E7-specific CD8+ T-cell immune responses and antitumor effects against an E7-expressing tumor, TC-1, in C57BL/6 tumor-bearing mice. Furthermore, a similar enhancement in E7-specific immune responses was observed by the co-administration of CRT–E7 DNA with DNA encoding other types of xenogenic MHC class-I molecules. This strategy was also applicable to another antigenic system, ovalbumin. Further characterization of the injection site revealed that the co-administration of HLA-A2 DNA led to a significant increase in the number of infiltrating CD8+ T lymphocytes and CD11b/c+ antigen-presenting cells. Furthermore, the E7-specific immune responses generated by intramuscular co-administration of CRT–E7 with HLA-A2 DNA were reduced in HLA-A2 transgenic mice. Thus, our data suggest that intramuscular co-administration of DNA encoding xenogenic MHC class-I can further improve the antigen-specific immune responses, as well as antitumor effects generated by DNA vaccines through enhancement of cross-priming mechanisms.

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Acknowledgements

This work was supported by the American Cancer Society (CF Hung) and National Cancer Institute SPORE in Cervical Cancer P50 CA098252 and the 1 RO1 CA114425-01 (T-C Wu).

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Authors and Affiliations

  1. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    T H Kang, A Monie, C-F Hung & T-C Wu

  2. Tissue Array Research Program, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    J-Y Chung

  3. Department of Otolaryngology/Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    S I Pai

  4. Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    C-F Hung & T-C Wu

  5. Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    T-C Wu

  6. Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    T-C Wu

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  1. T H Kang
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Correspondence to T-C Wu.

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Kang, T., Chung, JY., Monie, A. et al. Enhancing DNA vaccine potency by co-administration of xenogenic MHC class-I DNA. Gene Ther 17, 531–540 (2010). https://doi.org/10.1038/gt.2009.152

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