The ID93 + GLA-3M-052-LS vaccine candidate elicits mucosal and systemic immunogenicity and protective efficacy against Mycobacterium tuberculosis challenge in BCG-primed Collaborative Cross inbred mice

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ABSTRACT New vaccine approaches are needed against tuberculosis (TB). We sought to optimize mucosal immunogenicity and protective efficacy by modulating the adjuvant component and route of immunization of a next-generation TB vaccine using the recombinant TB vaccine antigen (Ag) ID93. ID93-specific mucosal and systemic immunogenicity and protective efficacy were assessed in the Collaborative Cross 004 mouse strain, a mouse strain susceptible to Mycobacterium tuberculosis ( Mtb ) infection, as a suitable model of Mtb susceptible populations. Immunogenicity data from various vaccine candidates were used to select lead vaccine candidates with the most preferred immunostimulatory profiles using a pre-determined desirability index. A liposomal adjuvant system containing synthetic TLR4 and TLR7/8 ligands (GLA-3M-052-LS), administered by a heterologous intramuscular-intranasal regimen, induced an optimal comprehensive immune response profile including high levels of mucosal antibody and Th1 CD4 + T cells in the lungs. In BCG-primed mice, immunization with intramuscular followed by intranasal ID93 + GLA-3M-052-LS boosts significantly reduced Mtb burden in the lungs after challenge vs. BCG vaccinated mice alone. Thus, ID93 + GLA-3M-052-LS represents a promising next-generation TB vaccine candidate suitable for testing in additional preclinical models.

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