Mycobacterium tuberculosis is a disease that infects millions of people each year; in addition, the related bacterium, Mycobacterium bovis, infects domesticated animals, resulting in substantial economic losses. Currently, humans are administered Bacille Calmette-Guerin (BCG) vaccine to prevent tuberculosis. However, BCG vaccines have variable efficacy - on average about 50%. Recombinant BCG vaccines have been developed that express a key antigen of M. tuberculosis and are more potent than BCG. However, these recombinant BCG vaccines contain antibiotic resistance markers; regulatory authorities want vaccines to be free of such antibiotic resistance markers to diminish their dissemination to other pathogens in the environment. Unmarked vaccine vectors (i.e. those lacking an antibiotic resistance marker) have been produced by various means, but these methods have resulted in low levels of expression of recombinant proteins. Preferably, unmarked strains would not only express large amounts of the recombinant proteins, but express them from genes integrated into the chromosome because such constructs tend to be more stable than when the genes are expressed from a plasmid. Due to safety, potency, regulatory, and stability issues, there is a need for a better vaccine that can prevent and treat tuberculosis in humans and animals.
Investigators at UCLA have identified a method of producing unmarked, live recombinant vaccine vectors that provide high expression of recombinant proteins from genes stably integrated into the chromosome.
The vaccine has been tested on animals.
|United States Of America||Issued Patent||8932846||01/13/2015||2007-715|
tuberculosis, recombinant vaccine, unmarked vector, BCG