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Editor’s note iNature is China’s largest academic official account.
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
.
iNature Bacille Calmette-Guerin (BCG) is a live attenuated vaccine with insufficient protection against tuberculosis (TB), and its basic mechanism is still unclear
.
Therefore, it is very urgent and important to clarify the mechanism of BCG failure so as to develop a better vaccine to effectively control tuberculosis (TB)
.
On October 27, 2021, Fan Xionglin's team from Tongji Medical College of Huazhong University of Science and Technology published an online publication titled "Deletion of BCG_2432c from the Bacillus Calmette- Guérin vaccine enhances autophagy- mediated immunity against tuberculosis" in Allergy (IF=13, Division 1 of the Chinese Academy of Sciences) Research article, this study proved for the first time that BCG_2432c is an important autophagy suppressor gene, which exists in a variety of commercial BCG strains, and knocking out BCG_2432c (ΔBCG-2432c) in BCG may improve the efficacy of BCG
.
The recombinant BCG vaccine ΔBCG-2432c is expected to replace the current BCG or develop more recombinant vaccines to improve global tuberculosis control and establish a scientific basis for clinical transformation
.
Autophagy is considered to be an important anti-tuberculosis defense mechanism to kill intracellular Mycobacterium tuberculosis.
Autophagy-mediated degradation can promote antigen presentation by antigen presenting cells (APC) through the MHC II molecular pathway
.
In addition, apoptosis plays an important role in controlling the spread of Mycobacterium tuberculosis in vivo, and apoptotic vesicles can activate CD8+ T cell responses through cross-presentation
.
Therefore, both autophagy and apoptosis can enhance the host's adaptive immune response to TB
.
However, under physiological conditions, the intracellular BCG strain does not autophagy and can only induce apoptosis of APC cells
.
It is hypothesized that the BCG vaccine may have inherited the immune escape strategy from the parental Mycobacterium bovis, leading to reduced efficacy against tuberculosis
.
The study identified immune escape genes related to apoptosis and autophagy from different BCG substrains, and then evaluated the impact of these immune escape mechanisms on the efficacy of BCG vaccines
.
Firstly, three genes related to immune escape, BCG_3174, BCG_1782 and BCG_2432c, were identified, and these three genes were knocked out respectively, and their effects on autophagy and their protective effects against tuberculosis infection were compared in vitro and in vivo
.
The article pattern picture (picture from Allergy) found that compared with BCG vaccine, mice immunized with only ΔBCG_2432c have stronger resistance to intranasal tuberculosis infection
.
The improved protection may be due to the early production and increase of IFN-γ+CD4+TEM and IL-2+CD4+TCM cells in the spleen and lungs of ΔBCG_2432c immunized mice
.
In order to further clarify the role of BCG_2432c, a study was carried out at the cellular level, and it was found that THP-1 cells infected by ΔBCG_2432c can induce intracellular ROS and mediate a complete autophagy flow, leading to higher antigen presentation in phagocytic antigen presenting cells
.
Research conclusion: The insufficient efficacy of BCG vaccine may be because the important autophagy suppressor gene BCG_2432c blocks the autophagosome-lysosome pathway and affects the ability of antigen presentation
.
ΔBCG_2432c provides a promising platform that is expected to replace the current BCG vaccine or develop a more effective anti-tuberculosis vaccine
.
Reference message: https://onlinelibrary.
wiley.
com/doi/10.
1111/all.
15158
It is jointly created by the doctoral team of Tsinghua University, Harvard University, Chinese Academy of Sciences and other units.
The iNature Talent Official Account is now launched, focusing on talent recruitment, academic progress, scientific research information, interested parties can Long press or scan the QR code below to follow us
.
iNature Bacille Calmette-Guerin (BCG) is a live attenuated vaccine with insufficient protection against tuberculosis (TB), and its basic mechanism is still unclear
.
Therefore, it is very urgent and important to clarify the mechanism of BCG failure so as to develop a better vaccine to effectively control tuberculosis (TB)
.
On October 27, 2021, Fan Xionglin's team from Tongji Medical College of Huazhong University of Science and Technology published an online publication titled "Deletion of BCG_2432c from the Bacillus Calmette- Guérin vaccine enhances autophagy- mediated immunity against tuberculosis" in Allergy (IF=13, Division 1 of the Chinese Academy of Sciences) Research article, this study proved for the first time that BCG_2432c is an important autophagy suppressor gene, which exists in a variety of commercial BCG strains, and knocking out BCG_2432c (ΔBCG-2432c) in BCG may improve the efficacy of BCG
.
The recombinant BCG vaccine ΔBCG-2432c is expected to replace the current BCG or develop more recombinant vaccines to improve global tuberculosis control and establish a scientific basis for clinical transformation
.
Autophagy is considered to be an important anti-tuberculosis defense mechanism to kill intracellular Mycobacterium tuberculosis.
Autophagy-mediated degradation can promote antigen presentation by antigen presenting cells (APC) through the MHC II molecular pathway
.
In addition, apoptosis plays an important role in controlling the spread of Mycobacterium tuberculosis in vivo, and apoptotic vesicles can activate CD8+ T cell responses through cross-presentation
.
Therefore, both autophagy and apoptosis can enhance the host's adaptive immune response to TB
.
However, under physiological conditions, the intracellular BCG strain does not autophagy and can only induce apoptosis of APC cells
.
It is hypothesized that the BCG vaccine may have inherited the immune escape strategy from the parental Mycobacterium bovis, leading to reduced efficacy against tuberculosis
.
The study identified immune escape genes related to apoptosis and autophagy from different BCG substrains, and then evaluated the impact of these immune escape mechanisms on the efficacy of BCG vaccines
.
Firstly, three genes related to immune escape, BCG_3174, BCG_1782 and BCG_2432c, were identified, and these three genes were knocked out respectively, and their effects on autophagy and their protective effects against tuberculosis infection were compared in vitro and in vivo
.
The article pattern picture (picture from Allergy) found that compared with BCG vaccine, mice immunized with only ΔBCG_2432c have stronger resistance to intranasal tuberculosis infection
.
The improved protection may be due to the early production and increase of IFN-γ+CD4+TEM and IL-2+CD4+TCM cells in the spleen and lungs of ΔBCG_2432c immunized mice
.
In order to further clarify the role of BCG_2432c, a study was carried out at the cellular level, and it was found that THP-1 cells infected by ΔBCG_2432c can induce intracellular ROS and mediate a complete autophagy flow, leading to higher antigen presentation in phagocytic antigen presenting cells
.
Research conclusion: The insufficient efficacy of BCG vaccine may be because the important autophagy suppressor gene BCG_2432c blocks the autophagosome-lysosome pathway and affects the ability of antigen presentation
.
ΔBCG_2432c provides a promising platform that is expected to replace the current BCG vaccine or develop a more effective anti-tuberculosis vaccine
.
Reference message: https://onlinelibrary.
wiley.
com/doi/10.
1111/all.
15158
