The combination of Mycobacterium tuberculosis fusion proteins LT33 and LT28 induced strong protective immunity in mice

Effective subunit vaccines for tuberculosis (TB) must target antigenic components at various stages of infection. In this study, we constructed fusion proteins using secreted antigens from Mycobacterium tuberculosis (M. tuberculosis), specifically ESAT6, CFP10, MPT64, and Rv2645 from the proliferati...

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Main Authors: Pu He, Juan Wang, Daquan Tan, Lina Hu, Yanlin Ma, Youjun Mi, Fei Li, Tingting Zhang, Yunjie Du, Wenhua Zhang, Jixi Li, Lei Jiao, Bingdong Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1450124/full
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author Pu He
Juan Wang
Daquan Tan
Lina Hu
Yanlin Ma
Youjun Mi
Youjun Mi
Fei Li
Tingting Zhang
Yunjie Du
Wenhua Zhang
Jixi Li
Lei Jiao
Bingdong Zhu
Bingdong Zhu
author_facet Pu He
Juan Wang
Daquan Tan
Lina Hu
Yanlin Ma
Youjun Mi
Youjun Mi
Fei Li
Tingting Zhang
Yunjie Du
Wenhua Zhang
Jixi Li
Lei Jiao
Bingdong Zhu
Bingdong Zhu
author_sort Pu He
collection DOAJ
description Effective subunit vaccines for tuberculosis (TB) must target antigenic components at various stages of infection. In this study, we constructed fusion proteins using secreted antigens from Mycobacterium tuberculosis (M. tuberculosis), specifically ESAT6, CFP10, MPT64, and Rv2645 from the proliferation stage, along with latency-associated antigens Rv1738 and Rv1978. The resulting fusion proteins, designated LT33 (ESAT6-CFP10-Rv1738) and LT28 (MPT6461-170-Rv19788-60-Rv264521-80), were combined with an adjuvant containing dimethyldioctadecylammonium bromide (DDA), polyriboinosinic polyribocytidylic acid (PolyI:C), and cholesterol to construct subunit vaccines. We evaluated the subunit vaccine effect in C57BL/6 mice and revealed that LT33 and LT28 exhibited strong immunogenicity and induced protective efficacy against aerosol challenge with M. tuberculosis H37Rv. Notably, the combination of LT33 and LT28 led to a significant reduction of 0.77 log10 colony-forming units (CFU) of H37Rv in the lungs compared to the adjuvant control group, highlighting their potential as promising candidates for subunit vaccine against M. tuberculosis infection.
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spelling doaj-art-20117aa0265246f6a4d84f34b39efb5a2024-11-22T06:16:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-11-011510.3389/fimmu.2024.14501241450124The combination of Mycobacterium tuberculosis fusion proteins LT33 and LT28 induced strong protective immunity in micePu He0Juan Wang1Daquan Tan2Lina Hu3Yanlin Ma4Youjun Mi5Youjun Mi6Fei Li7Tingting Zhang8Yunjie Du9Wenhua Zhang10Jixi Li11Lei Jiao12Bingdong Zhu13Bingdong Zhu14State Key Laboratory for Animal Disease Control and Prevention and Lanzhou Center for Tuberculosis Research, Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaState Key Laboratory for Animal Disease Control and Prevention and Lanzhou Center for Tuberculosis Research, Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaState Key Laboratory for Animal Disease Control and Prevention and Lanzhou Center for Tuberculosis Research, Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaLanzhou Institute of Biological Products, Lanzhou, ChinaState Key Laboratory for Animal Disease Control and Prevention and Lanzhou Center for Tuberculosis Research, Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaState Key Laboratory for Animal Disease Control and Prevention and Lanzhou Center for Tuberculosis Research, Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaInstitute of Pathogenic Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaState Key Laboratory for Animal Disease Control and Prevention and Lanzhou Center for Tuberculosis Research, Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaLanzhou Institute of Biological Products, Lanzhou, ChinaState Key Laboratory for Animal Disease Control and Prevention and Lanzhou Center for Tuberculosis Research, Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaSchool of Life Science, Lanzhou University, Lanzhou, ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, ChinaLanzhou Institute of Biological Products, Lanzhou, ChinaState Key Laboratory for Animal Disease Control and Prevention and Lanzhou Center for Tuberculosis Research, Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, ChinaCollege of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, ChinaEffective subunit vaccines for tuberculosis (TB) must target antigenic components at various stages of infection. In this study, we constructed fusion proteins using secreted antigens from Mycobacterium tuberculosis (M. tuberculosis), specifically ESAT6, CFP10, MPT64, and Rv2645 from the proliferation stage, along with latency-associated antigens Rv1738 and Rv1978. The resulting fusion proteins, designated LT33 (ESAT6-CFP10-Rv1738) and LT28 (MPT6461-170-Rv19788-60-Rv264521-80), were combined with an adjuvant containing dimethyldioctadecylammonium bromide (DDA), polyriboinosinic polyribocytidylic acid (PolyI:C), and cholesterol to construct subunit vaccines. We evaluated the subunit vaccine effect in C57BL/6 mice and revealed that LT33 and LT28 exhibited strong immunogenicity and induced protective efficacy against aerosol challenge with M. tuberculosis H37Rv. Notably, the combination of LT33 and LT28 led to a significant reduction of 0.77 log10 colony-forming units (CFU) of H37Rv in the lungs compared to the adjuvant control group, highlighting their potential as promising candidates for subunit vaccine against M. tuberculosis infection.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1450124/fullMycobacterium tuberculosissubunit vaccineantigenssecreted antigenlatency-associated antigen
spellingShingle Pu He
Juan Wang
Daquan Tan
Lina Hu
Yanlin Ma
Youjun Mi
Youjun Mi
Fei Li
Tingting Zhang
Yunjie Du
Wenhua Zhang
Jixi Li
Lei Jiao
Bingdong Zhu
Bingdong Zhu
The combination of Mycobacterium tuberculosis fusion proteins LT33 and LT28 induced strong protective immunity in mice
Frontiers in Immunology
Mycobacterium tuberculosis
subunit vaccine
antigens
secreted antigen
latency-associated antigen
title The combination of Mycobacterium tuberculosis fusion proteins LT33 and LT28 induced strong protective immunity in mice
title_full The combination of Mycobacterium tuberculosis fusion proteins LT33 and LT28 induced strong protective immunity in mice
title_fullStr The combination of Mycobacterium tuberculosis fusion proteins LT33 and LT28 induced strong protective immunity in mice
title_full_unstemmed The combination of Mycobacterium tuberculosis fusion proteins LT33 and LT28 induced strong protective immunity in mice
title_short The combination of Mycobacterium tuberculosis fusion proteins LT33 and LT28 induced strong protective immunity in mice
title_sort combination of mycobacterium tuberculosis fusion proteins lt33 and lt28 induced strong protective immunity in mice
topic Mycobacterium tuberculosis
subunit vaccine
antigens
secreted antigen
latency-associated antigen
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1450124/full
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