IP Library Granted Patent US 12661393
Granted Patent B2
US 12661393 · App. 18/029,599 · Granted Jun 23, 2026

BCG based vaccine compositions and methods of use thereof

Inventors: Alok Singh (Baltimore, MD); Peter Um (Baltimore, MD); Keira Cohen (Baltimore, MD); William Bishai (Baltimore, MD); Rulin Wang (Baltimore, MD); Srinivasan Yegnasubramanian (Baltimore, MD); Trinity J. Bivalacqua (Philadelphia, PA)
Assignee: The Johns Hopkins University
A61K39/04A61K35/74A61P31/14A61K2039/5254A61K2039/58
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Quick Facts
Patent No.
US 12661393
App. No.
18/029,599
Granted
Jun 23, 2026
Kind
B2
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.

Claims (17)

1 . A method of preventing, ameliorating or treating a viral infection in a subject comprising administering to the subject a recombinant bacille Calmette-Guerin (BCG) bacterial strain of Mycobacterium bovis comprising an exogenous nucleic acid construct comprising:

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 thereby treating the infection.

2 . The method of claim 1 , wherein the infection is a SARS-CoV-2 infection.

3 . The method of claim 1 , wherein the subject has a condition selected from the group consisting of obesity, diabetes, cystic fibrosis (CF), non-cystic-fibrosis bronchiectasis, and HIV/AIDS.

4 . The method of claim 1 , wherein the bacterial strain over expresses a stimulator of interferon genes (STING) agonist.

5 . The method of claim 4 , wherein the STING agonist is c-di-AMP.

6 . The method of claim 1 , wherein the disA gene is fused to the mycobacterial promoter.

7 . The method of claim 1 , wherein the nucleic acid construct does not have kanamycin resistance markers.

8 . The method of claim 1 , wherein the bacterial strain is optionally resistant to kanamycin.

9 . The method of claim 1 , wherein the bacterial strain comprises a selectable marker.

10 . The method of claim 1 , wherein the mycobacterial promoter is Hsp60 promoter.

11 . The method of claim 1 , wherein the exogenous nucleic acid construct further comprises a ppiA signal sequence and optionally a spike protein of SARS-COV-2.

12 . The method of claim 1 , wherein the exogenous nucleic acid construct further comprises a ppiA signal sequence and optionally the receptor binding domain of the spike protein of SARS-COV-2.

13 . The method of claim 11 , wherein the nucleic acid construct further comprises a signal peptide.

14 . The method of claim 13 , wherein the signal peptide comprises a ppiA signal sequence.