Prophylactic efficacy against Mycobacterium tuberculosis using ID93 and lipid-based adjuvant formulations in the mouse model.

An estimated 10 million people developed tuberculosis (TB) disease in 2019 which underscores the need for a vaccine that prevents disease and reduces transmission. The aim of our current studies is to characterize and test a prophylactic tuberculosis vaccine comprised of ID93, a polyprotein fusion antigen, and a liposomal formulation [including a synthetic TLR4 agonist (glucopyranosyl lipid adjuvant, GLA) and QS-21] in a preclinical mouse model of TB disease. Comparisons of the ID93+GLA-LSQ vaccines are also made to the highly characterized ID93+GLA-SE oil-in-water emulsion adjuvant, which are also included these studies. The recent success of vaccine candidate M72 combined with adjuvant AS01E (GlaxoSmithKline Biologicals) in reducing progression to active disease is promising and has renewed excitement for experimental vaccines currently in the TB vaccine pipeline. The AS01E adjuvant contains monophosphoryl lipid A (MPL) and QS-21 (a saponin) in a liposomal formulation. While AS01E has demonstrated potent adjuvant activity as a component of both approved and experimental vaccines, developing alternatives to this adjuvant system will become important to fill the high demand envisioned for future vaccine needs. Furthermore, replacement sources of potent adjuvants will help to supply the demand of a TB vaccine [almost one-quarter of the world's population are estimated to have latent Mycobacterium tuberculosis (Mtb) according to the WHO 2019 global TB report], addressing (a) cost of goods, (b) supply of goods, and (c) improved efficacy of subunit vaccines against Mtb. We show that both ID93+GLA-SE (containing an emulsion adjuvant) and ID93+GLA-LSQ (containing a liposomal adjuvant) induce ID93-specific TH1 cellular immunity including CD4+CD44+ T cells expressing IFNγ, TNF, and IL-2 (using flow cytometry and intracellular cytokine staining) and vaccine-specific IgG2 antibody responses (using an ELISA). In addition, both ID93+GLA-SE and ID93+GLA-LSQ effectively decrease the bacterial load within the lungs of mice infected with Mtb. Formulations based on this liposomal adjuvant formulation may provide an alternative to AS01 adjuvant systems.

Déclaration de conflit d'intérêts

The authors have read the journal’s policy and the authors of this manuscript have the following competing interests: EB is a paid employee of Umoja Biopharma, MTO is a paid employee of Bristol-Myers Squibb Co., and SGR is a paid employee of HDT Bio Corp. These authors were not employed by the listed organizations at the time the study was conducted. CBF is an inventor on patent applications involving QS-21 purification, GLA-LSQ, and GLA-SE (US 2017/032756; US 2018/049832), CBF, SGR, and SB are inventors on improved adjuvant formulations comprising TLR4 agonists and methods (EP2811981A1), SGR and RNC are inventors on patent applications involving ID93 (US 2017/9822152 and 2013/8486414), and SGR is on patents involving synthetic glucopyranosyl lipid adjuvants (US 2017/9814772). All other authors have declared that no competing interests exist. Shared material may require a MTA or license from the Infectious Disease Research Institute. This does not alter our adherence to PLOS ONE policies on sharing data and materials.