Toll-Like Receptor 9 Activation Rescues Impaired Antibody Response in Needle-free Intradermal DNA Vaccination

Abstract

The delivery of plasmid DNA to the skin can target distinct subsets of dermal dendritic cells to confer a superior immune response. The needle-free immunization technology offers a reliable, safe and efficient means to administer intradermal (ID) injections. We report here that the ID injection of DNA vectors using an NF device (NF-ID) elicits a superior cell-mediated immune response, at much lesser DNA dosage, comparable in magnitude to the traditional intramuscular immunization. However, the humoral response is significantly impaired, possibly at the stage of B cell isotype switching. We found that the NF-ID administration deposits the DNA primarily on the epidermis resulting in a rapid loss of the DNA as well as the synthesized antigen due to the faster regeneration rate of the skin layers. Therefore, despite the immune-rich nature of the skin, the NF-ID immunization of DNA vectors may be limited by the impaired humoral response. Additional booster injections are required to augment the antibody response. As an alternative and a viable solution, we rescued the IgG response by coadministration of a Toll-like receptor 9 agonist, among other adjuvants examined. Our work has important implication for the optimization of the emerging needle-free technology for ID immunization.

Potent Intradermal Gene Expression of Naked Plasmid DNA in Pig Skin Following Pyro-drive Jet Injection

“…Interest in ID immunization has increased in recent years because of technical advances in ID injections using jet injectors, which overcome the limitations associated with needle injections. 5 Jet injection can penetrate the skin and underlying tissues, leading to transfection of the affected areas, and shows potential for gene therapy applications. 6,7 The injection was efficient in promoting gene transfer, antigen expression, and immune responses in mouse and rat models.…”

“…6,7 The injection was efficient in promoting gene transfer, antigen expression, and immune responses in mouse and rat models. [5][6][7][8] However, although the studies using jet injection with small animals are promising, similar results are not always obtained in humans.…”