Induction of potent antitumor immunity by intradermal DNA injection using a novel needle-free pyro-drive jet injector

Abstract

The current success of mRNA vaccines against COVID-19 has highlighted the effectiveness of mRNA and DNA vaccinations. Recently, we demonstrated that a novel needle-free pyro-drive jet injector (PJI) effectively delivers plasmid DNA into the skin, resulting in protein expression higher than that achieved with a needle syringe. Here, we used ovalbumin (OVA) as a model antigen to investigate the potential of the PJI for vaccination against cancers. Intradermal injection of OVA-expression plasmid DNA into mice using the PJI, but not a needle syringe, rapidly and greatly augmented OVA-specific CD8⁺ T-cell expansion in lymph node cells. Increased mRNA expression of both interferon-γ and interleukin-4 and an enhanced proliferative response of OVA-specific CD8⁺ T cells, with fewer CD4⁺ T cells, were also observed. OVA-specific in vivo killing of the target cells and OVA-specific antibody production of both the IgG2a and IgG1 antibody subclasses were greatly augmented. Intradermal injection of OVA-expression plasmid DNA using the PJI showed stronger prophylactic and therapeutic effects against the progression of transplantable OVA-expressing E.G7-OVA tumor cells. Even compared with the most frequently used adjuvants, complete Freund's adjuvant and aluminum hydroxide with OVA protein, intradermal injection of OVA-expression plasmid DNA using the PJI showed a stronger CTL-dependent prophylactic effect. These results suggest that the novel needle-free PJI is a promising tool for DNA vaccination, inducing both a prophylactic and a therapeutic effect against cancers, because of prompt and strong generation of OVA-specific CTLs and subsequently enhanced production of both the IgG2a and IgG1 antibody subclasses.

Keywords: DNA vaccine; antitumor immunity; generation of CTLs; intradermal injection; pyro-drive jet injector.