Dataset Information

Immunogenicity and Vaccine Potential of InsB, an ESAT-6-Like Antigen Identified in the Highly Virulent Mycobacterium tuberculosis Beijing K Strain.

ABSTRACT: Our group recently identified InsB, an ESAT-6-like antigen belonging to the Mtb9.9 subfamily within the Esx family, in the Mycobacterium tuberculosis Korean Beijing strain (Mtb K) via a comparative genomic analysis with that of the reference Mtb H37Rv and characterized its immunogenicity and its induced immune response in patients with tuberculosis (TB). However, the vaccine potential of InsB has not been fully elucidated. In the present study, InsB was evaluated as a subunit vaccine in comparison with the most well-known ESAT-6 against the hypervirulent Mtb K. Mice immunized with InsB/MPL-DDA exhibited an antigen-specific IFN-? response along with antigen-specific effector/memory T cell expansion in the lungs and spleen upon antigen restimulation. In addition, InsB immunization markedly induced multifunctional Th1-type CD4+ T cells coexpressing TNF-?, IL-2, and IFN-? in the lungs following Mtb K challenge. Finally, we found that InsB immunization conferred long-term protection against Mtb K comparable to that conferred by ESAT-6 immunization, as evidenced by a similar level of CFU reduction in the lung and spleen and reduced lung inflammation. These results suggest that InsB may be an excellent vaccine antigen component for developing a multiantigenic Mtb subunit vaccine by generating Th1-biased memory T cells with a multifunctional capacity and may confer durable protection against the highly virulent Mtb K.

SUBMITTER: Kim WS

PROVIDER: S-EPMC6379281 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Immunogenicity and Vaccine Potential of InsB, an ESAT-6-Like Antigen Identified in the Highly Virulent <i>Mycobacterium tuberculosis</i> Beijing K Strain.

Kim Woo Sik WS Kim Hongmin H Kwon Kee Woong KW Cho Sang-Nae SN Shin Sung Jae SJ

Frontiers in microbiology 20190212

Our group recently identified InsB, an ESAT-6-like antigen belonging to the Mtb9.9 subfamily within the Esx family, in the <i>Mycobacterium tuberculosis</i> Korean Beijing strain (Mtb K) via a comparative genomic analysis with that of the reference Mtb H37Rv and characterized its immunogenicity and its induced immune response in patients with tuberculosis (TB). However, the vaccine potential of InsB has not been fully elucidated. In the present study, InsB was evaluated as a subunit vaccine in c ...[more]

PMID: 30809214

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Project description:The Beijing family of Mycobacterium tuberculosis is dominant in countries in East Asia. Genomic polymorphisms are a source of diversity within the M. tuberculosis genome and may account for the variation of virulence among M. tuberculosis isolates. Till date there are no studies that have examined the genomic composition of M. tuberculosis isolates from the high TB-burden country, Myanmar.Twenty-two M. tuberculosis isolates from Myanmar were screened on whole-genome arrays containing genes from M. tuberculosis H37Rv, M. tuberculosis CDC1551 and M. bovis AF22197. Screening identified 198 deletions or extra regions in the clinical isolates compared to H37Rv. Twenty-two regions differentiated between Beijing and non-Beijing isolates and were verified by PCR on an additional 40 isolates. Six regions (Rv0071-0074 [RD105], Rv1572-1576c [RD149], Rv1585c-1587c [RD149], MT1798-Rv1755c [RD152], Rv1761c [RD152] and Rv0279c) were deleted in Beijing isolates, of which 4 (Rv1572-1576c, Rv1585c-1587c, MT1798-Rv1755c and Rv1761c) were variably deleted among ST42 isolates, indicating a closer relationship between the Beijing and ST42 lineages. The TbD1 region, Mb1582-Mb1583 was deleted in Beijing and ST42 isolates. One M. bovis gene of unknown function, Mb3184c was present in all isolates, except 11 of 13 ST42 isolates. The CDC1551 gene, MT1360 coding for a putative adenylate cyclase, was present in all Beijing and ST42 isolates (except 1). The pks15/1 gene, coding for a putative virulence factor, was intact in all Beijing and non-Beijing isolates, except in ST42 and ST53 isolates.This study describes previously unreported deletions/extra regions in Beijing and non-Beijing M. tuberculosis isolates. The modern and highly frequent ST42 lineage showed a closer relationship to the hypervirulent Beijing lineage than to the ancient non-Beijing lineages. The pks15/1 gene was disrupted only in modern non-Beijing isolates. This is the first report of an in-depth analysis on the genomic diversity of M. tuberculosis isolates from Myanmar.

Dataset Information

Immunogenicity and Vaccine Potential of InsB, an ESAT-6-Like Antigen Identified in the Highly Virulent Mycobacterium tuberculosis Beijing K Strain.

Publications

Immunogenicity and Vaccine Potential of InsB, an ESAT-6-Like Antigen Identified in the Highly Virulent <i>Mycobacterium tuberculosis</i> Beijing K Strain.

Similar Datasets

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