IND-directed advancement of BCG-sting, a recombinant BCG overexpressing a sting agonist, as a next-generation tuberculosis vaccine

The National Institute of Allergy and Infectious Diseases awarded The Johns Hopkins University $984,124 on August 10, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) for advancement of BCG-STING, a recombinant Bacillus Calmette-Guerin vaccine candidate engineered to overexpress a STING agonist as a next-generation tuberculosis vaccine.

The project funds development and testing of BCG-STING to improve upon the efficacy and safety profile of conventional BCG vaccine. BCG-STING secretes excess c-di-AMP, a potent STING agonist that stimulates innate and acquired immune responses. Preclinical studies in mouse, guinea pig, and non-human primate models of tuberculosis demonstrate that BCG-STING is more potent than wild-type BCG and safer in mouse models. The vaccine candidate can be produced by fermentation, addressing current production limitations of conventional BCG.

Performance occurs at Baltimore, Maryland, with a period of performance extending through July 31, 2031. This is a Project Grant, the standard assistance type for research under NIAID's Allergy and Infectious Diseases Research program.

Abstract

Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, resulting in approximately 10 million cases and 1.5 million associated deaths per year. TB cases are on the rise due in part to HIV-TB CO- infection, the evolution of drug-resistant strains of mycobacterium tuberculosis (MTB), and interruptions to TB diagnostics and treatment access. This includes the U.S., where the number of infections has grown over the past five years. TB vaccination remains the most cost-effective method of controlling the disease, and an effective TB vaccination strategy therefore remains a crucial public health need. Bacillus calmette-guérin (BCG), an attenuated strain of mycobacterium bovis, is the only vaccine currently available against TB and is perhaps the most widely administered vaccine in history, with >5 billion doses administered worldwide since its introduction in 1921. BCG has a partially protective effect against active TB, helping to prevent disseminated and meningeal TB in children, but providing highly variable (0% to 80%) protection against pulmonary TB in adults and adolescents. Thus, there is an urgent need to development new vaccines with enhanced efficacy against TB. The goal of this project is to advance BCG-sting, a new recombinant BCG (RBCG) strain that overexpresses a potent agonist of sting (stimulator of interferon genes), as a TB vaccine with improved efficacy and safety compared to conventional wild-type BCG (BCG-WT). BCG-sting secretes excess C-DI-AMP, a sting agonist which stimulates both innate and acquired immune responses. Studies show that BCG-sting is more potent in mouse, guinea PIG, and NHP models of TB than BCG and is also safer than BCG-WT in mouse models. Additionally, BCG-sting can be produced by fermentation, overcoming current BCG production limitations. A johns hopkins (JHU) biotechnology start-up-oncosting LLC-licensed the BCG-sting patents in 2018 and has raised ~$6M in NIH and NSF sbir/sttr funding. Oncosting has retained the same cdmo which developed the GMP manufacturing methods for VPM1002, and that group will be ready to make frozen GMP- grade BCG-sting drug product by 2026. In 2021, NIH funded the drafting of an extensive TB vaccine product development plan (PDP) for BCG-sting, providing a clear-cut roadmap towards first-in-human studies. This project represents a JHU-oncosting collaborative effort to 1) assess the superiority of BCG-sting VS. BCG-WT in new cutting-edge models, 2) complete additional PDP-recommended studies to enable preparation of a preclinical data package commensurate with those of other live-attenuated mycobacteria vaccines tested clinically, and 3) complete the work needed to prepare for submission of an investigational new drug (IND) application by the end of the project period. On completion of this project, we anticipate that BCG-sting will be poised to initiate first-in-human studies for TB prevention.