ArticlePloS one2016
High Sequence Variability of the ppE18 Gene of Clinical Mycobacterium tuberculosis Complex Strains Potentially Impacts Effectivity of Vaccine Candidate M72/AS01E.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Complete genomes reveal a refined map of Mycobacterium tuberculosis genetic diversity across evolutionary scales.Nature communications · 2026Article
- The PE/PPE family proteins ofFrontiers in immunology · 2025Review
- The BCG vaccine, advantages, and disadvantages of introducing new generation vaccines againstClinical and experimental vaccine research · 2024Review
- Enhancing TB Vaccine Efficacy: Current Progress on Vaccines, Adjuvants and Immunization Strategies.Vaccines · 2023Review
- The Mycobacterium tuberculosis genome at 25 years: lessons and lingering questions.The Journal of clinical investigation · 2023Review
- Functional genetic variation inFrontiers in microbiology · 2023Article
- Therapeutic Potentials of Immunometabolomic Modulations Induced by Tuberculosis Vaccination.Vaccines · 2022Review
- Article
- Evaluation of the consistence between the results of immunoinformatics predictions and real-world animal experiments of a new tuberculosis vaccine MP3RT.Frontiers in cellular and infection microbiology · 2022Article
- Systematic Evaluation of Mycobacterium tuberculosis Proteins for Antigenic Properties Identifies Rv1485 and Rv1705c as Potential Protective Subunit Vaccine Candidates.Infection and immunity · 2021Article
- Peptides-Based Vaccine MP3RT Induced Protective Immunity AgainstFrontiers in immunology · 2021Article
- Tuberculosis vaccine development: from classic to clinical candidates.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2020Review
- New insights into the mycobacterial PE and PPE proteins provide a framework for future research.Molecular microbiology · 2020Review
- Predicted Structural Variability ofFrontiers in microbiology · 2020Article
- Mycobacterial virulence: impact on immunogenicity and vaccine research.F1000Research · 2019Review
- The Enigmatic PE/PPE Multigene Family of Mycobacteria and Tuberculosis Vaccination.Infection and immunity · 2017Review
- Immunological consequences of strain variation within the Mycobacterium tuberculosis complex.European journal of immunology · 2017Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of an effective vaccine is urgently needed to fight tuberculosis (TB) which is still the leading cause of death from a single infectious agent worldwide. One of the promising vaccine candidates M72/AS01E consists of two proteins subunits PepA and PPE18 coded by Rv0125 and Rv1196. However, preliminary data indicate a high level of sequence variability among clinical Mycobacterium tuberculosis complex (MTBC) strains that might have an impact on the vaccine efficacy. To further investigate this finding, we determined ppE18 sequence variability in a well-characterized reference collection of 71 MTBC strains from 23 phylogenetic lineages representing the global MTBC diversity. In total, 100 sequence variations consisting of 96 single nucleotide polymorphisms (SNPs), three insertions and one deletion were detected resulting in 141 variable positions distributed over the entire gene. The majority of SNPs detected were non-synonymous (n = 68 vs. n = 28 synonymous). Strains from animal adapted lineages, e.g., M. bovis, showed a significant higher diversity than the human pathogens such as M. tuberculosis Haarlem. SNP patterns specific for different lineages as well as for deeper branches in the phylogeny could be identified. The results of our study demonstrate a high variability of the ppE18 gene even in the N-terminal domains that is normally highly conserved in ppe genes. As the N-terminal region interacts with TLR2 receptor inducing a protective anti-inflammatory immune response, genetic heterogeneity has a potential impact on the vaccine efficiency, however, this has to be investigated in future studies.
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