Vol 65: 109 Problems and prospects of development of the subunit TB vaccine.Report as inadecuate



 Vol 65: 109 Problems and prospects of development of the subunit TB vaccine.


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This article is from Journal of Acquired Immune Deficiency Syndromes 1999, volume 65.AbstractTuberculosis TB causes about 1.4 million deaths each year. Currently the only licensed anti-tuberculosis vaccine is Bacille Calmette-Guérin BCG. This live attenuated vaccine has been in use for over 80 years and has displayed up to 80% efficacy against serious forms of the disease, eg, meningitis, in children. However, efficacy in adults against pulmonary tuberculosis ranges from 0% to 80% in different trials. The protective immunity generated by BCG decreases with time, and almost disappears after 20–25 years, resulting in a vulnerability of the adult population to primary infection and reactivation of latent TB. Thus, development of an effective preventive vaccine and new -post-infection- vaccine are still important aims of vaccinology.In this study we report the development of novel subunit protein-based vaccine against tuberculosis. Our vaccine consists of two recombinant mycobacterium proteins—Ag85A and fusion protein ESAT6-CFP10. These antigens are strongly recognized by T cells and they have demonstrated protective efficacy in animal models. However, because the protein component of the subunit vaccine is poorly immunogenic, the recombinant protein vaccine was adjuvanted with novel, 3-component adjuvant system composed of the dextran, cationic DEAE-dextran and oligodeoxynucleotide CpG. This adjuvant was chosen on the basis of its ability to induce strong protective immunity in animal models of M. tuberculosis infection, by delivering a TLR9 ligand into the endosomal pathway. Recombinant vaccine proteins possess dextran-binding domain, which helps create -depot- effect and provide prolonged interaction of vaccine antigen with T-cells.We investigated immunogenicity and protection properties of our vaccine on mice and guinea pigs models of tuberculosis, and also performed toxicity studies. We demonstrated that our subunit vaccine stimulates th1 immune response and is protective against tuberculosis with the same efficacy as BCG. Furthermore, our vaccine showed good result in toxicity studies in mice, guinea pigs and rabbits.



Author: Tkachuk, A.B.; Lunin, V.G.; Karyagina, A.S.; Gintsburg, A.L.

Source: https://archive.org/







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