Consequence of enhanced LC3-trafficking for a live, attenuated M. tuberculosis vaccine

Stefan Köster, Thais Klevorn, Kadamba Papavinasasundaram, Christopher M. Sassetti, Cynthia Portal-Celhay, Jennifer A. Philips

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Pages (from-to)939-944
Number of pages6
JournalVaccine
Volume36
Issue number7
DOIs
StatePublished - Feb 8 2018

Keywords

  • Autophagy
  • Auxotroph
  • BCG
  • Innate immunity
  • LC3-associated phagocytosis
  • Live attenuated vaccine
  • Tuberculosis

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