Culture filtrate proteins from BCG act as adjuvants for cytotoxic T lymphocyte induction

Mycobacterium bovis bacilli Calmette-Guerin (BCG) is a licensed vaccine against tuberculosis. It requires attenuated live bacteria to be effective, possibly because actively secreted proteins play a critical role in inducing anti-tuberculosis immunity. BCG also functions as an effective adjuvant. Mo...

Full description

Bibliographic Details
Main Authors: Satoru Mizuno, Yasushi Chuma, Yukihiro Shibuya, Shigeo Horibata, Tomoe Baba, Emi Yokokawa, Kazuhiro Matsuo
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1271228/full
_version_ 1827791292005875712
author Satoru Mizuno
Yasushi Chuma
Yukihiro Shibuya
Shigeo Horibata
Tomoe Baba
Emi Yokokawa
Kazuhiro Matsuo
Kazuhiro Matsuo
author_facet Satoru Mizuno
Yasushi Chuma
Yukihiro Shibuya
Shigeo Horibata
Tomoe Baba
Emi Yokokawa
Kazuhiro Matsuo
Kazuhiro Matsuo
author_sort Satoru Mizuno
collection DOAJ
description Mycobacterium bovis bacilli Calmette-Guerin (BCG) is a licensed vaccine against tuberculosis. It requires attenuated live bacteria to be effective, possibly because actively secreted proteins play a critical role in inducing anti-tuberculosis immunity. BCG also functions as an effective adjuvant. Moreover, the effects of BCG components as adjuvants are not important as those of attenuated live BCG, which is used in cancer immunotherapy. However, the BCG secreted proteins have not been paid attention in anticancer immunity. To understand mycobacterial secreted proteins’ function, we investigate immune responses to BCG culture filtrate proteins (CFP). Here, CFP strongly induce both antigen-specific CD4+ T cells and specific CD8+ T cells, which may be functional cytotoxic T lymphocytes (CTLs). In this study, we clearly demonstrate that CFP acts as an adjuvant for CTL induction against specific co-administered proteins and propose CFP as a new protein adjuvant. The CTL response shows potent anticancer effects in mice. These findings could provide insight into the contribution of mycobacterial secreted proteins in both anticancer and antimycobacterial immunity.
first_indexed 2024-03-11T17:45:07Z
format Article
id doaj.art-b0f7ffbd898b44ed8e5915e49ecf9e1d
institution Directory Open Access Journal
issn 1664-3224
language English
last_indexed 2024-03-11T17:45:07Z
publishDate 2023-10-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj.art-b0f7ffbd898b44ed8e5915e49ecf9e1d2023-10-18T08:30:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12712281271228Culture filtrate proteins from BCG act as adjuvants for cytotoxic T lymphocyte inductionSatoru Mizuno0Yasushi Chuma1Yukihiro Shibuya2Shigeo Horibata3Tomoe Baba4Emi Yokokawa5Kazuhiro Matsuo6Kazuhiro Matsuo7Research and Development Department, Japan BCG Laboratory, Kiyose, Tokyo, JapanResearch and Development Department, Japan BCG Laboratory, Kiyose, Tokyo, JapanResearch and Development Department, Japan BCG Laboratory, Kiyose, Tokyo, JapanResearch and Development Department, Japan BCG Laboratory, Kiyose, Tokyo, JapanResearch and Development Department, Japan BCG Laboratory, Kiyose, Tokyo, JapanResearch and Development Department, Japan BCG Laboratory, Kiyose, Tokyo, JapanResearch and Development Department, Japan BCG Laboratory, Kiyose, Tokyo, JapanInstitute for Vaccine Research and Development, Hokkaido University, Sapporo, Hokkaido, JapanMycobacterium bovis bacilli Calmette-Guerin (BCG) is a licensed vaccine against tuberculosis. It requires attenuated live bacteria to be effective, possibly because actively secreted proteins play a critical role in inducing anti-tuberculosis immunity. BCG also functions as an effective adjuvant. Moreover, the effects of BCG components as adjuvants are not important as those of attenuated live BCG, which is used in cancer immunotherapy. However, the BCG secreted proteins have not been paid attention in anticancer immunity. To understand mycobacterial secreted proteins’ function, we investigate immune responses to BCG culture filtrate proteins (CFP). Here, CFP strongly induce both antigen-specific CD4+ T cells and specific CD8+ T cells, which may be functional cytotoxic T lymphocytes (CTLs). In this study, we clearly demonstrate that CFP acts as an adjuvant for CTL induction against specific co-administered proteins and propose CFP as a new protein adjuvant. The CTL response shows potent anticancer effects in mice. These findings could provide insight into the contribution of mycobacterial secreted proteins in both anticancer and antimycobacterial immunity.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1271228/fullcytotoxic T lymphocytesculture filtrate proteintuberculosisMycobacterium bovis bacilli Calmette-Guerinimmunotherapy
spellingShingle Satoru Mizuno
Yasushi Chuma
Yukihiro Shibuya
Shigeo Horibata
Tomoe Baba
Emi Yokokawa
Kazuhiro Matsuo
Kazuhiro Matsuo
Culture filtrate proteins from BCG act as adjuvants for cytotoxic T lymphocyte induction
Frontiers in Immunology
cytotoxic T lymphocytes
culture filtrate protein
tuberculosis
Mycobacterium bovis bacilli Calmette-Guerin
immunotherapy
title Culture filtrate proteins from BCG act as adjuvants for cytotoxic T lymphocyte induction
title_full Culture filtrate proteins from BCG act as adjuvants for cytotoxic T lymphocyte induction
title_fullStr Culture filtrate proteins from BCG act as adjuvants for cytotoxic T lymphocyte induction
title_full_unstemmed Culture filtrate proteins from BCG act as adjuvants for cytotoxic T lymphocyte induction
title_short Culture filtrate proteins from BCG act as adjuvants for cytotoxic T lymphocyte induction
title_sort culture filtrate proteins from bcg act as adjuvants for cytotoxic t lymphocyte induction
topic cytotoxic T lymphocytes
culture filtrate protein
tuberculosis
Mycobacterium bovis bacilli Calmette-Guerin
immunotherapy
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1271228/full
work_keys_str_mv AT satorumizuno culturefiltrateproteinsfrombcgactasadjuvantsforcytotoxictlymphocyteinduction
AT yasushichuma culturefiltrateproteinsfrombcgactasadjuvantsforcytotoxictlymphocyteinduction
AT yukihiroshibuya culturefiltrateproteinsfrombcgactasadjuvantsforcytotoxictlymphocyteinduction
AT shigeohoribata culturefiltrateproteinsfrombcgactasadjuvantsforcytotoxictlymphocyteinduction
AT tomoebaba culturefiltrateproteinsfrombcgactasadjuvantsforcytotoxictlymphocyteinduction
AT emiyokokawa culturefiltrateproteinsfrombcgactasadjuvantsforcytotoxictlymphocyteinduction
AT kazuhiromatsuo culturefiltrateproteinsfrombcgactasadjuvantsforcytotoxictlymphocyteinduction
AT kazuhiromatsuo culturefiltrateproteinsfrombcgactasadjuvantsforcytotoxictlymphocyteinduction