Stage of Development

Proof of Concept – Animal Model

Vaccine Platform

Mycobacterial – Live Attenuated

Candidate Overview

BCG::ESAT6-PE25SS is a recombinant BCG strain generated on the Danish background. The strain was constructed by fusing the ESAT-6-encoding gene esxA to the general secretion signal for the mycobacterial type VII secretion pathway protein PE25. BCG::ESAT6-PE25SS secretes full-length ESAT-6 via the ESX-5 secretion system, which in contrast to ESX-1 is also present in BCG.

Sponsor / Lead Developer: James Cook University

Primary Indication: Prevention of TB disease

Other Indication(s): Immunotherapy/Shortening TB treatment and Prevention of TB recurrence

Target Population(s): Adolescents, Adults, Children, and Infants

Immune tissue localization: Lung and Lymph node

Immunological responses: B-cell/Antibody, Innate, and T-cell

Preclinical Animal Models: Mouse and Rabbit

Intended to elicit trained immunity: Yes

Additional Immunologic Response Information

Immune ResponseB-cell
T-cell phenotypeCD4
T-cell functional profileIFN-γ
Preferential immune tissue localizationLymph nodeLung
Trained immunityYesNo

Additional Information

In vivo testing revealed that ESX-5-targeted ESAT-6 export, induces cytosolic contact, generates ESAT-6-specific T cells and enhances the protective efficacy against TB disease, but is associated with low virulence and reduced persistence in immunocompetent and immunocompromised mice. Additionally, compared to BCG::ESX1Mtb and parental BCG, mucosal administration of BCG::ESAT6-PE25SS is associated with more rapid clearance from the lung and lower histopathology.

The vaccine candidate is currently undergoing testing in rabbit models of cavitary TB and therapeutic use in conjunction with antimicrobial therapy and host-directed therapy. It will also be tested in guinea pigs in 2024.

Additional unpublished results include protective efficacy in a diet-induced murine model of type 2 diabetes and a murine model designed to study reactivation of latent lymphatic TB.

The vaccine candidate is one of 6 live attenuated TB vaccine candidates currently evaluated head-to-head in 3 mouse models (C57BL/6, C3HeB/FeJ, SCID) at 4 independent sites around the world. Unblinding of results is expected in 2024.

An integrated Product Development Plan, Target Product Profiles and Stage Gating have been prepared for this candidate by TBVI.