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Efficient delivery of DNA vaccines using human papillomavirus pseudovirions

Gene Therapy volume 17, pages 1453–1464 (2010)Cite this article

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Abstract

We have examined non-replicative human papillomavirus (HPV) pseudovirions as an approach in the delivery of naked DNA vaccines without safety concerns associated with live viral vectors. In this study, we have generated HPV-16 pseudovirions encapsidating a DNA vaccine encoding the model antigen, ovalbumin (OVA) (HPV16-OVA pseudovirions). Vaccination with HPV16-OVA pseudovirions subcutaneously elicited significantly stronger OVA-specific CD8+ T-cell immune responses compared with OVA DNA vaccination via gene gun in a dose-dependent manner. We showed that a single amino acid mutation in the L2 minor capsid protein that eliminates the infectivity of HPV16-OVA pseudovirion significantly decreased the antigen-specific CD8+ T-cell responses in vaccinated mice. Furthermore, a subset of CD11c+ cells and B220+ cells in draining lymph nodes became labeled on vaccination with fluorescein isothiocyanate-labeled HPV16-OVA pseudovirions in injected mice. HPV pseudovirions were found to infect bone marrow-derived dendritic cells (BMDCs) in vitro. We also showed that pretreatment of HPV16-GFP pseudovirions with furin leads to enhanced HPV16-OVA pseudovirion infection of BMDCs and OVA antigen presentation. Our data suggest that DNA vaccines delivered using HPV pseudovirions represent an efficient delivery system that can potentially affect the field of DNA vaccine delivery.

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Acknowledgements

We thank Balasubramanyam Karanam and Subhashini Jagu for their assistance in the preparation of the pseudovirions. This work was supported by 1 RO1 CA114425 01 (Wu), 1 RO1 CA118790 (Roden) and SPORE programs (P50 CA098252 and P50 CA96784-06) of the National Cancer Institute.

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Authors and Affiliations

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

    S Peng, A Monie, T H Kang, C-F Hung, R Roden & T-C Wu

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

    R Roden & T-C Wu

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

    R Roden & T-C Wu

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

    T-C Wu

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  1. S Peng
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Correspondence to T-C Wu.

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Peng, S., Monie, A., Kang, T. et al. Efficient delivery of DNA vaccines using human papillomavirus pseudovirions. Gene Ther 17, 1453–1464 (2010). https://doi.org/10.1038/gt.2010.106

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