期刊
INFECTION AND IMMUNITY
卷 86, 期 7, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.00014-18
关键词
Mycobacterium tuberculosis; tuberculosis; vaccines; viral vectors
资金
- FP7 grant NEWTBVAC [241745]
- European Union's Horizon 2020 research and innovation program [643381]
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. Department of Health and Human Services [HHSN272200900053C, HHSN266200400081C]
- [095780/Z/11/Z]
- H2020 Societal Challenges Programme [643381] Funding Source: H2020 Societal Challenges Programme
The development of a vaccine against tuberculosis (TB), a disease caused by Mycobacterium tuberculosis, is urgently needed. The only currently available vaccine, M. bovis BCG, has variable efficacy. One approach in the global vaccine development effort is focused on boosting BCG using subunit vaccines. The identification of novel antigens for inclusion in subunit vaccines is a critical step in the TB vaccine development pathway. We selected four novel mycobacterial antigens recognized during the course of human infection. A replication-deficient chimpanzee adenovirus (ChAdOx1) was constructed to express each antigen individually, and these vectors were evaluated for protective efficacy in murine M. tuberculosis challenge experiments. One antigen, PPE15 (Rv1039c), conferred significant and reproducible protection when administered alone and as a boost to BCG vaccination. We identified immunodominant epitopes to define the protective immune responses using tetramers and intravascular staining. Lung parenchymal CD4(+) and CD8(+) CXCR3(+) KLRG1(-) T cells, previously associated with protection against M. tuberculosis, were enriched in the vaccinated groups compared to the control groups. Further work to evaluate the protective efficacy of PPE15 in more stringent preclinical animal models, together with the identification of further novel protective antigens using this selection strategy, is now merited.
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