Mycobacterium tuberculosis Antigen Rv1471 Induces Innate Immune Memory and Adaptive Immunity Against Infection

Area of Science:

• Immunology
• Vaccinology
• Microbiology

Background:

• Mycobacterium tuberculosis (Mtb) has ~4000 proteins, but only ~100 are explored as subunit vaccine antigens.
• No subunit tuberculosis (TB) vaccine targeting trained immunity has been developed.
• Rv1471, an Mtb-secreted thioredoxin, is investigated for its potential to stimulate macrophage maturation.

Purpose of the Study:

• To evaluate Rv1471 as a candidate antigen for a trained immunity-targeting subunit TB vaccine.
• To investigate the molecular pathways activated by Rv1471 in trained macrophages.
• To assess the protective efficacy of Rv1471 against Mtb infection in a murine model.

Main Methods:

• Macrophage culture and Rv1471 stimulation.
• Transcriptional analysis of Rv1471-trained macrophages (Akt-mTOR-HIF-1α and aerobic glycolysis pathways).
• Murine model of TB: immunization with Rv1471, Mtb challenge, and assessment of immune responses and protection.

Main Results:

• Rv1471-trained macrophages showed activated innate immune memory via Akt-mTOR-HIF-1α and aerobic glycolysis.
• Rv1471 enhanced innate immune memory and protection against intracellular mycobacterial infections.
• Immunization with Rv1471 in mice induced robust antigen-specific multifunctional T-cell responses and significant protection against Mtb.

Conclusions:

• Rv1471 effectively stimulates innate immune memory and T-cell responses.
• Rv1471 demonstrates protective efficacy in a murine model of TB.
• These findings support Rv1471 as a promising candidate for developing an innate immune memory-targeting subunit TB vaccine.