Use of GLA-nanoalum as an effective adjuvant for a therapeutic ID93 TB vaccine

Abstract Tuberculosis (TB) caused by the intracellular bacterium Mycobacterium tuberculosis (Mtb) reportedly killed 1.3 million people in 2016 and is the leading cause of death caused by a single infectious organism. Increasingly worrisome is the ability of Mtb to develop extensive drug resistance. According to the 2017 WHO global TB report, there were 600,000 new rifampicin-resistant cases in 2016, and almost half a million cases with multiple drug resistant (MDR) TB. The development of new host-targeted therapeutic strategies that prevent the outgrowth of resistant mutants and/or modulate the immune response to combat Mtb infection and/or reduce disease pathology is one solution to prevent the generation of antibacterial resistance and treat drug resistant (DR)-TB. Here we evaluate a novel nanoalum adjuvant formulation containing a synthetic TLR4 agonist, glucopyranosyl lipid adjuvant (GLA), with our clinical ID93 protein as an immunotherapeutic vaccine. We show that immunotherapy with ID93+GLA-nanoalum is effective against Mtb when given as an adjunct to drug treatment in a mouse TB therapy model.