Developing tuberculosis vaccines - challenges and strategies 2

Published on June 30, 2015   36 min

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So let's go through the global clinical pipeline of TB vaccine candidates. So 15 years ago, there were essentially no TB vaccines in the clinic, and due to stimulation of the field, mostly through large grants by the EC, European Community, and the Bill and Melinda Gates Foundation, there has been huge work and appreciation for the need to develop tuberculosis vaccines. And today we have a relatively rich pipeline. However, this pipeline is somewhat lacking in terms of its immunologic diversity, and we'll go through that in a second. The pipeline includes, as you see in sort of purple, the mycobacterial whole cell extracts, the most advanced of which is a non-tuberculosis Mycobacterium, similar to TB, which is in a Phase III trial in rural China. That's being studied in latency patients, that is, patients who have already been infected with TB to try to keep them from going on to either reactivating or going on to active tuberculosis. And that is a large Phase III trial in 10,000 people which should read out sometime in 2016. There have been Phase IIB trials, one of MVA85A, which I'll talk about shortly, as well as an ongoing Phase IIB trial of M72, a protein adjuvanted subunit. There are protein adjuvants which tend to dominate this in dark blue, and those are subunit vaccines containing somewhere between two to four antigens, which are always adjuvanted and given usually by intramuscular injection. And then there are the actual mycobacterial vaccines themselves, such as MTBVAC, an actual attenuated vaccine. So this is actually a live attenuated tuberculosis, which is being given intradermally, developed by BIOFABRI and the University of Zaragoza in Spain. We have DAR-901, which is another non-tuberculosis mycobacteria named Mycobacterium obuense. We have RUTI, which is a whole cell mycobacterial lysate. And then we have a variety of viral vectors shown in light purple, such as the MV85A, which is no longer advancing, the Crucell Ad35, human Ad35, expressing three antigens. There is an intranasal flu developed by the Russians. There is an Ad5 that is being developed to be given as an aerosol vaccine by the Chinese and CanSino, as well as a recombinant BCG, VPM1002, originally developed by Stefan Kaufmann at the Max Planck Institute in Germany, and now being further developed after being turned over from the Vaccine Project Management Organization in Germany over to the Serum Institute of India for further development.

Developing tuberculosis vaccines - challenges and strategies 2

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