Adjuvant Activity of CpG-Oligonucleotide Administered Transcutaneously in Combination with Vaccination Using a Self-Dissolving Microneedle Patch in Mice

• Published in: Vaccines (Basel) 2021-12, Vol.9 (12), p.1480
• Main Authors: Hirobe, Sachiko, Kawakita, Takuto, Yamasaki, Taki, Ito, Sayami, Tachibana, Masashi, Okada, Naoki
• Format: Article
• Language: English
• Subjects: adjuvant; Antibodies; Antigens; CD4 antigen; Cell activation; Cell differentiation; Cell proliferation; CpG islands; CpG-oligonucleotide; Effector cells; Experiments; Flow cytometry; Immune response; Immune system; Immunization; Immunoglobulin G; Immunological memory; Infectious diseases; Laboratory animals; Lymph nodes; Lymphocytes; Lymphocytes B; Lymphocytes T; Memory cells; microneedle; Needles; Oligonucleotides; Ovalbumin; Polyethylene terephthalate; Population studies; TLR9 ligand; transcutaneous immunization; Transgenic animals; Vaccination; Vaccines
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines9121480

In this study, we investigated the mechanism of transcutaneous adjuvant activity of the CpG-oligonucleotide (K3) in mice. Transcutaneous immunization (TCI) with an ovalbumin-loaded self-dissolving microneedle patch (OVA-sdMN) and K3-loaded hydrophilic gel patch (HG) increased OVA-specific Th2- and Th1-type IgG subclass antibody titers more rapidly and strongly than those after only OVA-sdMN administration. However, the antigen-specific proliferation of OVA-specific CD4 T cells was similar between the OVA-only and the OVA+K3 groups. Population analysis of various immune cells in draining lymph nodes (dLNs) in the primary immune response revealed that the OVA+K3 combination doubled the number of dLN cells, with the most significant increase in B cells. Phenotypic analysis by flow cytometry revealed that B-cell activation and maturation were promoted in the OVA+K3 group, suggesting that direct B-cell activation by K3 largely contributed to the rapid increase in antigen-specific antibody titer in TCI. In the secondary immune response, a significant increase in effector T cells and effector memory T cells, and an increase in memory B cells were observed in the OVA+K3 group compared with that in the OVA-only group. Thus, K3, as a transcutaneous adjuvant, can promote the memory differentiation of T and B cells.