BCG VACCINE

TB VACCINE

LIVE RECOMBINANT VACCINES:
Efforts to modify BCG or M. tuberculosis by recombinant DNA technology to produce a new live attenuated vaccine against TB are in progress. The following are the method used.
A) Express a variety of heterologus antigen.
B) Knocking out the genes in M. tuberculosis required for virulence or prolonged survival within macrophages.
C) Mutagenesis strategy to reproducibly obtain recombinants by allelic exchange in
M.tuberculosis
PEPTIDE VACCINES:
In order to develop an effective peptide vaccine for tuberculosis, the specific antigens must be identified, and their ability to induce protective immunity must be confirmed.
Mycobacterium tuberculosis is known to express numerous proteins, some of which are:
ESAT-6- as diagnostic reagent
30/32 kDa (85 complex) –involvement in Mycobacterium cell wall synthesis.
38 kDa (lipoprotein)
19 kDa (lipoprotein)
MPT64 (24 kDa)
Stress proteins (10 kDa, 65 kDa, 70 kDa, 90kDa)- used as recombinant antigens,they have capacity to elicit human T cell proliferation.
DNA VACCINES-
The DNA vaccine involves the use of either antigen encoding naked DNA in buffer solution, which has been proven to transfect cells in vivo, or a viral vector coding for specific disease antigens. The two antigens used for these vaccines are- heat shock protein 65 (hsp65) and antigen 85 (Ag85). Heat shock proteins are known antigens recognized most frequently in the immune responses to intracellular pathogens, including Mycobacteria. Ag85 is a protein complex composed of three proteins: Ag85A, Ag85B and Ag85C. The Ag85 complex belongs to a group of proteins secreted actively by dividing Mycobacteria known to stimulate early and strong cellular immune responses in humans and mice infected with M. tuberculosis
Other vaccines currently in development are:
MVA85A
rBCG30
72F fusion protein
ESAT6-Ag85b fusion protein
MVA85A
MVA85A (modified vaccinia Ankara 86A) is a new-generation vaccine against tuberculosis developed by researchers at Oxford University. This vaccine is especially effective when used together with the old TB vaccine called BCG.
 
RBCG30
 rBCG30 (recombinant Bacillus Calmette-Guérin 30) is a prospective vaccine against tuberculosis created by a team headed by Marcus A. Horwitz at UCLA. It is a live vaccine, consisting of BCG genetically modified to produce abundant amounts of a 30kDa antigen that has been shown to produce a strong immune response in animals and humans.
72F fusion protein
72F fusion protein is a candidate tuberculosis vaccine created by SSI. The 72F fusion protein is composed of the Rv0125 and Rv1196 proteins derived from Mycobacterium tuberculosis. Phase I clinical trials were completed in 2005 and Phase II trials are awaited.