CD4+ T Cells Recognizing PE/PPE Antigens Directly or via Cross Reactivity Are Protective against Pulmonary...

Area of Science:

• Immunology
• Microbiology
• Vaccinology

Background:

• Mycobacterium tuberculosis (Mtb) utilizes type VII secretion systems (ESX-1, -3, -5) in pathogenesis.
• An attenuated Mtb vaccine candidate (Mtb Δppe25-pe19) lacks ESX-5-associated PE/PPE genes but retains other ESX-5 components.
• Previous studies showed this candidate induces CD4+ T-cell responses against non-ESX-5 PE/PPE homologs, with cross-recognition of missing ESX-5 PE/PPE proteins.

Purpose of the Study:

• To characterize the functional cross-reactive Th1 effector subsets specific to shared PE/PPE epitopes in mice immunized with Mtb Δppe25-pe19.
• To compare the immune response elicited by the attenuated Mtb Δppe25-pe19 strain with the wild-type (WT) Mtb strain.

Main Methods:

• Immunization of mice with the Mtb Δppe25-pe19 vaccine candidate.
• Characterization of Th1 effector subsets using flow cytometry and immunological assays.
• Assessment of immune stimulation of innate and adaptive immune responses.

Main Results:

• The Mtb Δppe25-pe19 strain elicited a comparable antigenic repertoire to WT Mtb regarding ESX systems.
• The induced Th1 effector subset composition and differentiation status were similar between the attenuated and WT Mtb strains.
• PE/PPE-specific Th1 effector cells significantly contributed to protective immunity against pulmonary Mtb infection.

Conclusions:

• The live attenuated Mtb Δppe25-pe19 vaccine candidate induces robust Th1 immune responses comparable to WT Mtb.
• Shared PE/PPE epitopes are crucial for cross-reactive T-cell responses and protective immunity.
• PE/PPE proteins hold significant potential as immunogens for developing effective tuberculosis vaccines.