Development of novel recombinant BCG vaccine and its immunological analysis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09946
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Nihon University
• Principal Investigator: AIZAWA Shihoko 日本大学, 医学部, 准教授 (30513858)
• Co-Investigator(Kenkyū-buntansha): 本多 三男 日本大学, 医学部, 研究員 (20117378) ; 早川 智 日本大学, 医学部, 教授 (30238084)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 抗酸菌 / 結核 / BCG / 細胞傷害性T細胞 / ヘルパーT細胞 / 非結核性抗酸菌

Outline of Final Research Achievements

To improve immunization against the persistent health challenge of Mycobacterium tuberculosis (Mtb) infection, we have studied the CD8+ T cell response to Bacillus Calmette-Guerin (BCG) and recombinant BCG (rBCG) in mice. Here, we generated CD8+ T cells with an rBCG-based vaccine encoding the Ag85B protein of M. kansasii, termed rBCG-Mkan85B, followed by boosting with plasmid DNA expressing the Ag85B gene (DNA-Mkan85B). We identified two MHC-I (H2-Kd)-restricted epitopes which induce cross-reactive responses to Mtb and other related mycobacteria. Tetramer staining indicated that the two H2-Kd-restricted epitopes elicit distinct CD8+ T cell populations, a result explained by the X-ray structure of the two peptide/H2-Kd complexes. These results suggest that rBCG-Mkan85B vector-based immunization and DNA-Mkan85B boost may enhance CD8+ T cell response to Mtb, and might help to overcome the limited effectiveness of the current BCG in eliciting tuberculosis immunity.

Free Research Field

感染免疫

Academic Significance and Societal Importance of the Research Achievements

結核の防御は国民衛生上重要な課題の一つである。結核ワクチンとしてBCGが古くから使われているが、成人におけるBCGの効果の限界が示唆されており、より効果的な結核ワクチンの開発・実用化が待たれている。本研究で作成した組換えBCGは既存のBCGよりも強力に結核抗原特異的T細胞を誘導できることから、新たな結核ワクチンの候補となりうる。また、近年患者数が増加傾向にある非結核性抗酸菌症のワクチンとなる可能性も示唆された。