Consequence of enhanced LC3-trafficking for a live, attenuated M. tuberculosis vaccine. Issue 7 (8th February 2018)

• Record Type: Journal Article
• Authors: Köster, Stefan; Klevorn, Thais; Papavinasasundaram, Kadamba; Sassetti, Christopher M.; Portal-Celhay, Cynthia; Philips, Jennifer A.
• Is Part Of: Vaccine. Volume 36:Issue 7(2018)
• Page Start: 939
• Page End: 944
• Publication Date: 2018-02-08
• Subjects: LAP LC3-associated phagocytosis; Tuberculosis -- BCG -- Autophagy -- LC3-associated phagocytosis -- Innate immunity -- Live attenuated vaccine -- Auxotroph; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2018.01.012
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Auxotrophic M. tuberculosis vaccine, mc 2 6206, inhibits LC3-trafficking. CpsA, a LytR-CpsA-Psr protein, inhibits LC3-trafficking in mc 2 6206. ESX-1 is required for LC3-trafficking in the vaccine strain. Enhanced LC3-trafficking enhances protection from disseminated infection. 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 mc 2 6206 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.