The immune responses induced by BCG vaccination in the non-human primate TB model

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08968
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: National Institute of Infectious Diseases (2020-2022); National Institutes of Biomedical Innovation, Health and Nutrition (2019)
• Principal Investigator: Tsujimura Yusuke 国立感染症研究所, ハンセン病研究センター 感染制御部, 主任研究官 (30512404)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 結核 / BCG / カニクイザル

Outline of Final Research Achievements

The crucial point is that observation of efficacy for vaccine candidates in a non-human primate (NHP) model of Mtb infection is required to advance the candidates to clinical studies. In this study, cynomolgus macaques were used to assess immunogenicity, course of infection and protection against Mtb challenge following BCG i.d immunization. BCG is the only licensed vaccine currently. The primary goal of this study was to establish an ideal monkey model of Mtb infection that reflects the preventive effects of BCG observed in humans. In our NHP TB model, BCG vaccination could not prevent pulmonary TB showing an increase of the bacterial burden in the lungs and aggravation of granulomas quality, although the vaccination provided complete protection against extrapulmonary dissemination of TB. Factors reflecting vaccine efficacy and pathophysiology were not found in immunological or biochemical analyses in our NHP model.

Free Research Field

免疫学　ワクチン学

Academic Significance and Societal Importance of the Research Achievements

現在、15種類のワクチン候補が第2相臨床試験のパイプラインに乗っているが実用化されたものはない。また、結核ワクチンの防御効果と相関する指標がないことが開発を困難にしていると考えられる。そこで本実験では、ヒト結核病変を再現でき、また後ろ向き実験も可能なカニクイザルを用いて結核感染実験をすることで結核病態やワクチン効果に相関する要因を解析し、結核の撲滅に向けた基盤づくりを目指した。また、ヒト結核モデルであるカニクイザルを用いた動物実験を行うことは、ヒトへの実用化をも視野に入れた有意義な結果を導き出すことが可能であり、その成果として医学領域に大きく貢献できる知見が得られることが期待される。