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

Mycobacterium tuberculosis (Mtb) contains approximately 4000 individual proteins. However, only about 100 have been evaluated as antigens in tuberculosis (TB) subunit vaccine development. In addition, no trained immunity-targeting subunit TB vaccine has been reported yet. This study tested Rv1471, a thioredoxin secreted by Mtb, as a candidate TB vaccine antigen due to its capacity to stimulate functional maturation of macrophages. Transcription analysis of Rv1471-trained macrophages indicated that innate immune memory was activated through pathways of Akt-mTOR-HIF-1α and aerobic glycolysis. Rv1471 also enhanced innate immune memory responses and protection against intracellular infections of different mycobacteria. In a murine model of TB, immunization with Rv1471 produced robust antigen-specific multifunctional T-cell immune responses and had substantial protective efficacy against Mtb challenge. Analysis of recall immunity showed that the Rv1471 triggered robust T-cell immunity after Mtb infection. These findings support the development of an innate immune memory-targeting subunit TB vaccine to increase vaccine efficacy.