Tuberculosis(TB) has claimed 1.8 million human lives globally according to World Health Organization, in 2015. Despite Bacillus Calmette-Guerin (BCG) vaccine, the only available vaccine for TB, currently one-third of the world is latently infected with TB due to the incompetence of BCG in adults against Mycobacterium tuberculosis, the bacteria responsible for TB.
Researchers from University of Delhi developed a booster DNA vaccine expressing antigen-- Hsp-X or α-crystallin, a protein expressed by the bacteria, and tested it on animal models. Here, the vaccine was seen to reduce the load of infectious bacteria in lungs and spleen, consequently reducing antigen load and pathological damage. But the performance of the DNA vaccine in humans was not as promising as it was in the animal models.
To overcome this, the team developed a recombinant virus expressing M. tuberculosis antigen, α-crystallin. Here the antigen basically stimulates the body’s immune system to recognize it as a threat, destroy it and have a memory of it, destroying any of the microorganisms associated with the agent that it may encounter in the future. The protein was cloned in a plasmid transfer vector (pSC65.gfp.acr.DR) which was transfected into Modified Vaccinia Ankara (MVA), the protein delivery vehicle used in this study. Plasmids are DNA molecules within a cell that can replicate independently from the DNA in the chromosome. After screening and purification, the efficacy of the recombinant rMVA.acr viruses was assessed by boosting BCG vaccinated guinea pigs with rMVA.acr and was checked for bacterial load in the lungs and other pathological changes.
As the dose and route of administration has determining effect on efficacy of the vaccine, various routes such as intradermal, intramuscular and intranasal was checked for a range of dosages. It was found that the vaccine provides better protection via intradermal and intramuscular routes, while and intranasal vaccination did not enhance the protection. The efficacy of the vaccine was also checked by increasing the bacterial load.
“Further evaluation of the vaccines is required to understand the long term protection efficiency of the vaccine in guinea pigs” say the researchers about the future direction of their work.