A Promising Needle-Free Pyro-Drive Jet Injector for Augmentation of Immunity by Intradermal Injection as a Physical Adjuvant.

Current worldwide mRNA vaccination against SARS-CoV-2 by intramuscular injection using a needled syringe has greatly protected numerous people from COVID-19. An intramuscular injection is generally well tolerated, safer and easier to perform on a large scale, whereas the skin has the benefit of the presence of numerous immune cells, such as professional antigen-presenting dendritic cells. Therefore, intradermal injection is considered superior to intramuscular injection for the induction of protective immunity, but more proficiency is required for the injection. To improve these issues, several different types of more versatile jet injectors have been developed to deliver DNAs, proteins or drugs by high jet velocity through the skin without a needle. Among them, a new needle-free pyro-drive jet injector has a unique characteristic that utilizes gunpower as a mechanical driving force, in particular, bi-phasic pyrotechnics to provoke high jet velocity and consequently the wide dispersion of the injected DNA solution in the skin. A significant amount of evidence has revealed that it is highly effective as a vaccinating tool to induce potent protective cellular and humoral immunity against cancers and infectious diseases. This is presumably explained by the fact that shear stress generated by the high jet velocity facilitates the uptake of DNA in the cells and, consequently, its protein expression. The shear stress also possibly elicits danger signals which, together with the plasmid DNA, subsequently induces the activation of innate immunity including dendritic cell maturation, leading to the establishment of adaptive immunity. This review summarizes the recent advances in needle-free jet injectors to augment the cellular and humoral immunity by intradermal injection and the possible mechanism of action.

Chemical- and Drug-Induced Allergic, Inflammatory, and Autoimmune Diseases Via Haptenation.

Haptens are small molecules that only elicit an immune response when bound to proteins. Haptens initially bind to self-proteins and activate innate immune responses by complex mechanisms via inflammatory cytokines and damage-associated molecular patterns and the subsequent upregulation of costimulatory signals such as cluster of differentiation 86 (CD86) on dendritic cells. Subsequent interactions between CD86 and CD28 on T cells are critically important for properly activating naive T cells and inducing interleukin 2 production, leading to the establishment of adaptive immunity via effector and memory T cells. Accumulating evidence revealed the involvement of haptens in the development of various autoimmune-like diseases such as allergic, inflammatory, and autoimmune diseases including allergic contact dermatitis, atopy, asthma, food allergy, inflammatory bowel diseases, hemolytic anemia, liver injury, leukoderma, and even antitumor immunity. Therefore, the development of in vitro testing alternatives to evaluate in advance whether a substance might lead to the development of these diseases is highly desirable. This review summarizes and discusses recent advances in chemical- and drug-induced allergic, inflammatory, and autoimmune diseases via haptenation and the possible molecular underlying mechanisms, as well as in vitro testing alternatives to evaluate in advance whether a substance might cause the development of these diseases.

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

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.