155 206

Cited 0 times in

BCGΔBCG1419c increased memory CD8+ T cell-associated immunogenicity and mitigated pulmonary inflammation compared with BCG in a model of chronic tuberculosis

 Kee Woong Kwon  ;  Michel de Jesús Aceves-Sánchez  ;  Cristian Alfredo Segura-Cerda  ;  Eunsol Choi  ;  Helle Bielefeldt-Ohmann  ;  Sung Jae Shin  ;  Mario Alberto Flores-Valdez 
 SCIENTIFIC REPORTS, Vol.12(1) : 15824, 2022-09 
Journal Title
Issue Date
Animals ; BCG Vaccine ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Interleukin-10 ; Interleukin-2 ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mycobacterium tuberculosis* ; Pneumonia* ; Tuberculin ; Tuberculosis* / microbiology ; Tumor Necrosis Factor-alpha
Previously, we reported that a hygromycin resistant version of the BCGΔBCG1419c vaccine candidate reduced tuberculosis (TB) disease in BALB/c, C57BL/6, and B6D2F1 mice infected with Mycobacterium tuberculosis (Mtb) H37Rv. Here, the second-generation version of BCGΔBCG1419c (based on BCG Pasteur ATCC 35734, without antibiotic resistance markers, and a complete deletion of BCG1419c) was compared to its parental BCG for immunogenicity and protective efficacy against the Mtb clinical isolate M2 in C57BL/6 mice. Both BCG and BCGΔBCG1419c induced production of IFN-γ, TNF-α, and/or IL-2 by effector memory (CD44+CD62L-), PPD-specific, CD4+ T cells, and only BCGΔBCG1419c increased effector memory, PPD-specific CD8+ T cell responses in the lungs and spleens compared with unvaccinated mice before challenge. BCGΔBCG1419c increased levels of central memory (CD62L+CD44+) T CD4+ and CD8+ cells compared to those of BCG-vaccinated mice. Both BCG strains elicited Th1-biased antigen-specific polyfunctional effector memory CD4+/CD8+ T cell responses at 10 weeks post-infection, and both vaccines controlled Mtb M2 growth in the lung and spleen. Only BCGΔBCG1419c significantly ameliorated pulmonary inflammation and decreased neutrophil infiltration into the lung compared to BCG-vaccinated and unvaccinated mice. Both BCG strains reduced pulmonary TNF-α, IFN-γ, and IL-10 levels. Taken together, BCGΔBCG1419c increased memory CD8+T cell-associated immunogenicity and mitigated pulmonary inflammation compared with BCG.
Files in This Item:
T202204722.pdf Download
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Advanced Medical Science Research and Education (첨단의과학교육연구단) > 1. Journal Papers
Yonsei Authors
Kwon, Kee Woong(권기웅)
Shin, Sung Jae(신성재) ORCID logo https://orcid.org/0000-0003-0854-4582
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.