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Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo

Gene Therapy volume 17, pages 72–82 (2010)Cite this article

Abstract

A hurdle facing DNA vaccine development is the ability to generate strong immune responses systemically and at local immune sites. We report a novel systemically administered DNA vaccination strategy using intramuscular codelivery of CCL27 or CCL28, which elicited elevated peripheral IFN-γ and antigen-specific IgG while driving antigen-specific T-cell secretion of cytokine and antibody production in the gut-associated lymphoid tissue and lung. This strategy resulted in induction of long-lived antibody responses that neutralized influenza A/PR8/34 and protected mice from morbidity and mortality associated with a lethal intranasal viral challenge. This is the first example of the use of CCL27 and CCL28 chemokines as adjuvants to influence a DNA vaccine strategy, suggesting further examination of this approach for manipulation of vaccine-induced immunity impacting both quality and phenotype of responses.

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Acknowledgements

We would like to thank the University of Pennsylvania Department of Pathology Histology Core and Daniel Martinez for their help with immunohistochemical analyses. We would also like to thank Dr Jean D Boyer for her scientific guidance. CCR10 knockout mice were a generous gift from Drs Craig Gerard and Olivier Morteau. Amy Quinn and Carolyn Clarke provided molecular cloning expertise. In addition, we would like to acknowledge Dr Walter Gerhard, Krystyna Mozdzanowska and Darya Zharikova for their helpful comments and expertise on influenza A/PR8/34 mouse studies and neutralization assays. We would like to thank Mr Albert Sylvester, Ms Noshin Kathuria, Philip Choe and Michelle Nater for their help in the mucosal immune assays and analysis. Dr Jiri Mestecky also contributed scientific guidance for the humoral analysis on mucosal tissue and fecal extracts. We would also like to acknowledge Pamela Fried and Diana Winters from Drexel University College of Medicine Academic Publishing Services for their editorial, formatting and journal submission expertise. This work is supported by grants funded through the National Institutes of Health including an F32AI054152 through NIAIDS (MK), an N01A1154 NIAIDS-HVDDT (DBW), an NIH-NIAID-HIVRAD grant (DBW) and a T32-A107632 (KAK).

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Author notes

  1. M A Kutzler and K A Kraynyak: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Infectious Diseases and HIV Medicine, The Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USA

    M A Kutzler

  2. The Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    K A Kraynyak, S J Nagle, R M Parkinson, H Maguire, K Muthumani & D B Weiner

  3. Wistar Institute, Philadelphia, PA, USA

    D Zharikova

  4. The Department of Internal Medicine, Johns Hopkins University, Baltimore, MD, USA

    M Chattergoon

  5. The Department of Molecular Medicine, University of South Florida, Tampa, FL, USA

    K Ugen

  6. Center for Molecular Delivery, University of South Florida, Tampa, FL, USA

    K Ugen

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  1. M A Kutzler
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Correspondence to D B Weiner.

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Kutzler, M., Kraynyak, K., Nagle, S. et al. Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo. Gene Ther 17, 72–82 (2010). https://doi.org/10.1038/gt.2009.112

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