Characteristic of K3 (CpG-ODN) as a Transcutaneous Vaccine Formulation Adjuvant.
Sayami ItoSachiko HirobeTakuto KawakitaMio SaitoYing-Shu QuanFumio KamiyamaKen J IshiiMizuho NagaoTakao FujisawaMasashi TachibanaNaoki OkadaPublished in: Pharmaceutics (2020)
Transcutaneous immunization (TCI) is easy to use, minimally invasive, and has excellent efficacy in vaccines against infections. We focused on toll-like receptor (TLR) ligands as applicable adjuvants for transcutaneous formulations and characterized immune responses. TCI was performed using poke-and-patch methods, in which puncture holes are formed with a polyglycolic acid microneedle on the back skin of mice. Various TLR ligands were applied to the puncture holes and covered with an ovalbumin-loaded hydrophilic gel patch. During the screening process, K3 (CpG-oligonucleotide) successfully produced more antigen-specific antibodies than other TLR ligands and induced T helper (Th) 1-type polarization. Transcutaneously administered K3 was detected in draining lymph nodes and was found to promote B cell activation and differentiation, suggesting a direct transcutaneous adjuvant activity on B cells. Furthermore, a human safety test of K3-loaded self-dissolving microneedles (sdMN) was performed. Although a local skin reaction was observed at the sdMN application site, there was no systemic side reaction. In summary, we report a K3-induced Th1-type immune response that is a promising adjuvant for transcutaneous vaccine formulations using MN and show that K3-loaded sdMN can be safely applied to human skin.
Keyphrases
- toll like receptor
- immune response
- wound healing
- drug delivery
- nuclear factor
- inflammatory response
- early stage
- high glucose
- minimally invasive
- lymph node
- dendritic cells
- endothelial cells
- diabetic rats
- dna methylation
- cancer therapy
- drug induced
- oxidative stress
- induced pluripotent stem cells
- soft tissue
- gene expression
- room temperature
- hyaluronic acid
- robot assisted
- mass spectrometry
- rectal cancer
- ionic liquid