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Strong immunogenicity and cross-reactivity of Mycobacterium tuberculosis ESX-5 type VII secretion: encoded PE-PPE proteins predicts vaccine potential.

Abstract : The genome of Mycobacterium tuberculosis (Mtb) encodes five type VII secretion systems, ESX-1 to ESX-5, most of which are associated with genes encoding PE/PPE proteins, named after their N-terminal Pro-Glu (PE) or Pro-Pro-Glu (PPE) motifs. Here, we describe the strong T cell immunogenicity of the ESX-5-encoded PE/PPE proteins, which share a large panel of cross-reactive CD4(+) epitopes with substantial numbers of their ESX-5-nonassociated PE/PPE homologs. The immunogenicity of these numerous PE/PPE proteins is dependent on their export by a functional EccD(5), the predicted transmembrane channel of the ESX-5 secretion apparatus. The Mtb Δppe25-pe19 mutant deleted for all ESX-5-associated pe and ppe genes, although highly attenuated in immunocompetent mice, remains able to induce immunity against the ESX-5-associated PE/PPE virulence factors, via cross-reactivity with their numerous homologs, and against the ESX-1 virulence factors ESAT-6/CFP-10. The Δppe25-pe19 strain is strongly protective against Mtb infection in mice and represents a potential antituberculosis vaccine candidate.
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Submitted on : Monday, January 19, 2015 - 11:33:31 AM
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Fadel Sayes, Lin Sun, Mariagrazia Di Luca, Roxane Simeone, Nathalie Degaiffier, et al.. Strong immunogenicity and cross-reactivity of Mycobacterium tuberculosis ESX-5 type VII secretion: encoded PE-PPE proteins predicts vaccine potential.. Cell Host and Microbe, Elsevier, 2012, 11 (4), pp.352-63. ⟨10.1016/j.chom.2012.03.003⟩. ⟨pasteur-01104794⟩

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