Characteristic of K3 (CpG-ODN) as a Transcutaneous Vaccine Formulation Adjuvant

Autor: Sayami Ito, Sachiko Hirobe, Takuto Kawakita, Mio Saito, Ying-Shu Quan, Fumio Kamiyama, Ken J. Ishii, Mizuho Nagao, Takao Fujisawa, Masashi Tachibana, Naoki Okada
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Pharmaceutics, Vol 12, Iss 3, p 267 (2020)
Druh dokumentu: article
ISSN: 1999-4923
DOI: 10.3390/pharmaceutics12030267
Popis: 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.
Databáze: Directory of Open Access Journals