BCG based vaccine compositions and methods of use thereof
Inventors
Singh, Alok • Um, Peter • Cohen, Keira • Bishai, William • Wang, Rulin • Yegnasubramanian, Srinivasan • Bivalacqua, Trinity J.
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Assignees
MemberJohns Hopkins UniversityJohns Hopkins UniversityFounded in 1876, Johns Hopkins University is recognized as the first research university in the United States. It advances interdisciplinary education, high-impact research, and global outreach, supporting knowledge translation, technological innovation, and community partnerships. The university fosters academic excellence, innovation incubation, outreach, and inclusion across multiple campuses in Baltimore, integrating into the city's social, economic, and cultural life.
Founded in 1876, Johns Hopkins University is recognized as the first research university in the United States. It advances interdisciplinary education, high-impact research, and global outreach, supporting knowledge translation, technological innovation, and community partnerships. The university fosters academic excellence, innovation incubation, outreach, and inclusion across multiple campuses in Baltimore, integrating into the city's social, economic, and cultural life.
Publication Number
US-12661393-B2
Publication Date
2026-06-23
Expiration Date
Abstract
The present disclosure relates to a BCG based therapeutic agent using a BCG strain that overexpresses the STING agonist, c-di-AMP. This BCG strain, called BCG-disA-OE, enhances the elevated trained immunity of macrophages and promotes early anti-viral Type I interferon responses in a subject, providing protection against viral infections such as primary respiratory infections and SARS-CoV-2 infection.
Core Innovation
A recombinant bacille Calmette-Guerin (BCG) bacterial strain of Mycobacterium bovis is engineered to comprise an exogenous nucleic acid construct with a mycobacterial promoter and a disA gene. The disA gene is a Mycobacterium tuberculosis gene, so that disA-driven generation of elevated cyclic di-AMP is used as a STING agonist activity.
The disclosed approach is applied to preventing, ameliorating, or treating a primary respiratory viral infection by administering the recombinant BCG strain carrying the disA construct. The described rationale and outcomes include promoted early Type I interferon responses and enhanced trained immunity of macrophages, including macrophage reprogramming toward M1 polarization and reduced M2/IL-10 profiles.
The document further describes that the disA overexpression/STING agonist axis supports reduced SARS-CoV-2 lung pathology in animal models and includes STING-dependent anti-tumor effects in a bladder cancer model. Reported changes include altered immune cell recruitment, reduced granulocyte infiltration, improved resolution of inflammation, and preservation or boosting of CD3/CD4 signals.
Claims Coverage
The partial claims content includes one independent claim with multiple dependent claim refinements. Overall, the inventive features center on administering a recombinant BCG (Mycobacterium bovis) strain containing an exogenous nucleic acid construct with a mycobacterial promoter and a Mycobacterium tuberculosis disA gene for treating a primary respiratory viral infection.
Recombinant BCG disA gene construct for primary respiratory viral infection
A method of preventing, ameliorating or treating a viral infection in a subject by administering a recombinant bacille Calmette-Guerin (BCG) bacterial strain of Mycobacterium bovis comprising an exogenous nucleic acid construct with a mycobacterial promoter and a disA gene, wherein the disA gene is a Mycobacterium tuberculosis gene, and wherein the viral infection is a primary respiratory infection.
The independent claim requires administration of a recombinant BCG (Mycobacterium bovis) strain containing an exogenous nucleic acid construct with a mycobacterial promoter and a Mycobacterium tuberculosis disA gene, for preventing, ameliorating, or treating a primary respiratory viral infection.
Stated Advantages
Promoted early Type I interferon responses.
Enhanced trained immunity of macrophages.
Reduced severity of SARS-CoV-2 lung pathology in animal models.
Improved resolution of inflammation with reduced granulocyte infiltration.
STING-dependent anti-tumor effects in the bladder cancer model.
Documented Applications
Prevention, amelioration or treatment of primary respiratory viral infections, including SARS-CoV-2 infection.
STING-dependent anti-tumor effects in a MB49 bladder cancer model in STING−/− mice.
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