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

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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.

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