| Literature DB >> 29343411 |
Stefan Köster1, Thais Klevorn1, Kadamba Papavinasasundaram2, Christopher M Sassetti2, Cynthia Portal-Celhay1, Jennifer A Philips3.
Abstract
Development of a new vaccine against tuberculosis is urgently needed. Recent work has demonstrated that two related LC3-associated trafficking pathways, autophagy and LC3-associated phagocytosis (LAP), enhance antigen presentation and might play a role in vaccine efficacy. Mycobacterium tuberculosis inhibits both LC3-trafficking pathways. Moreover, the vaccine strain, BCG, induces even less LC3-trafficking than M. tuberculosis, which may help explain its limited efficacy. To determine whether enhanced LC3-trafficking can improve efficacy of a live, attenuated M. tuberculosis vaccine, we took advantage of our recent finding that the bacterial virulence factor CpsA inhibits LAP. When we deleted cpsA in the mc26206 vaccine strain, it dramatically increased LC3-trafficking. We compared the protective efficacy of the strain lacking cpsA to the parent strain and to BCG in mice challenged with M. tuberculosis. We found that the strain lacking cpsA generated modestly enhanced protection in the spleen, but overall did not outperform BCG.Entities:
Keywords: Autophagy; Auxotroph; BCG; Innate immunity; LC3-associated phagocytosis; Live attenuated vaccine; Tuberculosis
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Year: 2018 PMID： 29343411 PMCID： PMC5930169 DOI： 10.1016/j.vaccine.2018.01.012
Source DB: PubMed Journal: Vaccine ISSN： 0264-410X Impact factor: 3.641