4.5 Article

Transcutaneous immunization with a highly active form of XCL1 as a vaccine adjuvant using a hydrophilic gel patch elicits long-term CD8+ T cell responses

期刊

JOURNAL OF PHARMACOLOGICAL SCIENCES
卷 143, 期 3, 页码 182-187

出版社

JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2020.04.004

关键词

Memory CTL; Chemokine; XCL1; Transcutaneous immunization; Adjuvant

资金

  1. MEXT (Ministry of Education, Culture, Sports, Science and Technology)supported Program for the Strategic Research Foundation at Private Universities, 2014-2018 [S1411037]
  2. Kindai University

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Memory CD8(+) cytotoxic T-lymphocytes (CTLs) play a key role in protective immunity against infection and cancer. However, the induction of memory CTLs with currently available vaccines remains difficult. The chemokine receptor XCR1 is predominantly expressed on CD103(+) cross-presenting dendritic cells (DCs). Recently, we have demonstrated that a high activity form of murine lymphotactin/XCL1 (mXCL1-V21C/A59C), a ligand of XCR1, can induce antigen-specific memory CTLs by increasing the accumulation of CD103+ DCs in the vaccination site and the regional lymph nodes. Here, we combined a hydrophilic gel patch as a transcutaneous delivery device and mXCL1-V21C/A59C as an adjuvant to further enhance memory CTL responses. The transcutaneous delivery of ovalbumin (OVA) and mXCL1-V21C/A59C by the hydrophilic gel patch increased CD103(+) DCs in the vaccination site and the regional lymph nodes for a prolonged period of time compared with the intradermal injection of OVA and mXCL1-V21C/A59C. Furthermore, the hydrophilic gel patch containing OVA and mXCL1-V21C/A59C strongly induced OVAspecific memory CTLs and efficiently inhibited the growth of OVA-expressing tumors more than the intradermal injection of OVA and mXCL1-V21C/A59C. Collectively, this type of hydrophilic gel patch and a high activity form of XCL1 may provide a useful tool for the induction of memory CTL responses. (C) 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.

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