Electroporation of skeletal muscle induces danger signal release and antigen-presenting cell recruitment independently of DNA vaccine administration

Abstract

Background: Plasmid DNA vaccination combined with electroporation (EP) provides a promising approach for the prevention of infectious diseases and for cancer immunotherapy. This technology has been described as being effective in activating humoural and cellular immune response in the host as well as in enhancing expression of the encoded antigen. Several reports showed EP has adjuvant-like properties when combined with plasmid DNA injection although the effect in the absence of DNA has not been investigated. Objective: The aim of this study is to clarify whether the application of EP alone to the skeletal muscle is able to recruit and trigger cells involved in antigen presentation and immune response. Methods: Mouse skeletal muscle treated by EP were observed and processed for clinical, histological and immunohistochemistry analysis at different time points. Results: We demonstrate that EP induces transient morphological changes in the muscle with early production of endogenous cytokines responsible for signalling danger at the local level. Moreover, it causes the recruitment of inflammatory cells independently of the DNA injection and the activation of a danger pro-inflammatory pathway, resulting in T-lymphocyte migration. Conclusions: Our data indicate EP by itself is able to recruit and trigger cells involved in antigen presentation and immune response; hence, the idea that EP has adjuvant-like properties owing to a moderate tissue injury and generation of a pro-inflammatory context with cytokine release that enhances the immune response. We suggest EP may be of practical use in clinical protocols, contributing to the development of DNA vaccination strategies.

Keywords::

• adjuvant
• antigen presentation
• dendritic cell
• DNA vaccine
• electroporation

Acknowledgements

We thank the following people of CIR, University Campus Bio-Medico of Rome: S Morini, F Keller, S Carotti and F Biamonte for providing the instrumental equipment for tissue sectioning and G Capriotti and S Virga for their administrative assistance. We also thank L Serafino (Institute of Neurobiology and Molecular Medicine, CNR, Rome) for the gift of the anti-CD8⁺/CD4⁺ antibodies. We are grateful to the people of the Animal Facility at the “Sacro Cuore” Catholic University of Rome for their assistance in animal care.

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