LIVE BACTERIAL VACCINES RESISTANT TO CARBON DIOXIDE (CO2), ACIDIC PH AND/OR OSMOLARITY FOR VIRAL INFECTION PROPHYLAXIS OR TREATMENT

摘要

Gram-negative bacterial mutants resistant to one or more stress conditions, including CO₂, acid pH, and high osmolarity, and more particularly to gram-negative bacterial mutants with reduced TNF-α induction having a mutation in one or more lipid biosynthesis genes, including, but not limited to msbB, that are rendered stress-resistant by a mutation in the zwf gene. Compositions are provided comprising one or more stress-resistant gram-negative bacterial mutants, preferably attenuated stress-resistant gram-negative bacterial mutants. Methods are provided for prophylaxis or treatment of a virally induced disease in a subject comprising administering to a subject a stress-resistant gram-negative bacterial mutants, preferably attenuated stress-resistant gram-negative bacterial mutants. The stress-resistant gram-negative bacterial mutants may serve as vectors for the delivery of one or more therapeutic molecules to a host. The methods of the invention provide more efficient delivery of therapeutic molecules by stress-resistant gram-negative bacterial mutants engineered to express said therapeutic molecules.