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

Abstract

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.

A two-dose optimum for recombinant S1 protein-based COVID-19 vaccination

“…AS01 was also included in the M72/AS01 tuberculosis subunit vaccine that gave high protection against disease progression in a phase 2b trial ( Tait et al, 2019 ). Recently, it was shown that liposomes containing MPL and QS21 potently enhanced the antibody response to recombinant SARS-CoV-2 RBD antigen in mice and rabbits ( Huang et al, 2020 ) and the addition of QS21 to a liposomal adjuvant (GLA-LS) formulated with tuberculosis recombinant poly-antigen ID93 enhanced IgG responses in mice ( Baldwin et al, 2021 ).…”

Adjuvants influence the maturation of VRC01-like antibodies during immunization

“…Polyinosinic-polycytidylic acid (Poly(I:C)) was obtained from InvivoGene. GLA-LSQ was provided by the Infectious Disease Research Institute (IDRI) and liposomal formulations of GLA were prepared as previously published ( Baldwin et al., 2021 ). Rehydragel was provided by the NIAID.…”

Adjuvants influence the maturation of VRC01-like antibodies during immunization

“…Polyinosinic-polycytidylic acid (Poly(I:C)) was obtained from InvivoGene. GLA-LSQ was provided by the Infectious Disease Research Institute (IDRI) and liposomal formulations of GLA were prepared as previously published ( 93 ). Rehydragel was provided by the NIAID.…”