Department of Microbiology, Institute for Immunology and Immunological Disease, Brain Korea 21 Program for Leading Universities and Students (PLUS) Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, South Korea.
FASEB J. 2019 May;33(5):6483-6496. doi: 10.1096/fj.201802604R. Epub 2019 Feb 12.
Calmette-Guerin vaccine confers insufficient pulmonary protection against tuberculosis (TB), particularly the (Mtb) Beijing strain infection. Identification of vaccine antigens (Ags) by considering Mtb genetic diversity is crucial for the development of improved TB vaccine. MTBK_20640, a new Beijing genotype-specific proline-glutamic acid-family Ag, was identified by comparative genomic analysis. Its immunologic features were characterized by evaluating interactions with dendritic cells (DCs), and immunogenicity and vaccine efficacy were determined against highly virulent Mtb Beijing outbreak Korean Beijing (K) strain and HN878 strain in murine infection model. MTBK_20640 induced DCs TLR2 and downstream MAPK and NF-κB signaling pathways, effectively promoting naive CD4-positive (CD4) T-cell proliferation and IFN-γ production. Different IFN-γ response was observed in mice infected with Mtb K or reference H37Rv strain. Significant induction of T helper type 1 cell-polarized Ag-specific multifunctional CD4 T cells and a marked Ag-specific IgG2c response were observed in mice immunized with MTBK_20640/glucopyranosyl lipid adjuvant-stable emulsion. The immunization conferred long-term protection against 2 Mtb Beijing outbreak strains, as evidenced by a significant reduction in colony-forming units in the lung and spleen and reduced lung inflammation. MTBK_20640 vaccination conferred long-term protection against highly virulent Mtb Beijing strains. MTBK_20640 may be developed into a novel Ag component in multisubunit TB vaccines in the future.-Kwon, K. W., Choi, H.-H., Han, S. J., Kim, J.-S., Kim, W. S., Kim, H., Kim, L.-H., Kang, S. M., Park, J., Shin, S. J. Vaccine efficacy of a Beijing-specific proline-glutamic acid (PE) antigen against highly virulent outbreak isolates.
卡介苗对结核病（TB）的肺部保护作用不足，特别是针对 （Mtb）北京株感染。考虑到 Mtb 遗传多样性，通过鉴定疫苗抗原（Ags）对于开发改良型 TB 疫苗至关重要。通过比较基因组分析，鉴定了一种新的北京基因型特异性脯氨酸-谷氨酸家族 Ag，MTBK_20640。通过评估与树突状细胞（DCs）的相互作用，以及在鼠感染模型中针对高毒力 Mtb 北京暴发韩国北京（K）株和 HN878 株的免疫原性和疫苗效力，对其免疫特性进行了表征。MTBK_20640 诱导 DCs 表达 TLR2 及其下游 MAPK 和 NF-κB 信号通路，有效促进幼稚 CD4 阳性（CD4）T 细胞增殖和 IFN-γ产生。在感染 Mtb K 株或参考 H37Rv 株的小鼠中观察到不同的 IFN-γ反应。在 MTBK_20640/葡糖苷脂佐剂稳定乳剂免疫的小鼠中，观察到强烈诱导 Th1 细胞极化 Ag 特异性多功能 CD4 T 细胞和明显的 Ag 特异性 IgG2c 反应。MTBK_20640 免疫赋予了针对 2 株北京暴发 Mtb 的长期保护，这表现为肺部和脾脏中的菌落形成单位显著减少以及肺部炎症减轻。MTBK_20640 疫苗赋予针对高毒力 Mtb 北京株的长期保护。MTBK_20640 可能会在未来成为多亚单位 TB 疫苗中的新型 Ag 成分。-Kwon，KW，Choi，HH，Han，SJ，Kim，JS，Kim，WS，Kim，H，Kim，LH，Kang，SM，Park，J，Shin，SJ。针对高毒力暴发分离株的北京特异性脯氨酸-谷氨酸（PE）抗原的疫苗效力。
