2020 Fiscal Year Final Research Report

Development of a novel vaccine against intracellular bacterial infection by inhibiting immune checkpoint molecules

Research Project

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Project/Area Number	18H02818
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 53030:Respiratory medicine-related
Research Institution	Hamamatsu University School of Medicine
Principal Investigator	Suda Takafumi 浜松医科大学, 医学部, 教授 (30291397)
Co-Investigator(Kenkyū-buntansha)	藤澤朋幸浜松医科大学, 医学部, 助教 (20402357) 榎本紀之浜松医科大学, 医学部附属病院, 講師 (50436961) 中村祐太郎浜松医科大学, 医学部附属病院, 講師 (60436962) 永田年浜松医科大学, 医学部, 教授 (90275024)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	免疫チェックポイント / ワクチン / 樹状細胞 / PD1/PD-L1 / 細胞内寄生菌
Outline of Final Research Achievements	This study was conducted to develop a powerful cell vaccine against intracellular bacterial infection such as tuberculosis by inhibiting immune check-point molecules that acts as an immune brake. Dendritic cells (BMDCs) cultured from mouse bone marrow strongly express PD-L1, and when mice are inoculated with a cell vaccine in which this BMDC is pulsed with the dominant epitope LLO91-99 of Listeria, administration of anti-PD-1 antibody together induced antigen-specific cytotoxic T cells more efficiently, and enhanced the antigen-specific IFNγ-producing ability. However, in the Listeria monocytogenes-infection model, enhanced protective immunity against Listeria by the administration of anti-PD-1 antibody could not be confirmed.
Free Research Field	呼吸器内科学
Academic Significance and Societal Importance of the Research Achievements	免疫チェックポイン分子を阻害する治療 (ICI) は，生体の免疫を高めて抗腫瘍免疫を増強する新たながんの治療法として，現在，がん治療のパラダイムシフトを起こしている．我々は，全く新たな視点から，このICIを，がんではなく，感染症に対するワクチンの効果を増強する方法として利用することを考えた．そこで，いまだ有効なワクチンのない結核を含む細胞内寄生菌感染症に対して，生体で最も強力な抗原提示細胞である樹状細胞ワクチンを用いて，その効果をICI併用によって高めるICI併用細胞ワクチンの開発に挑んだ．