Einstein awarded $6 million grant to develop new TB vaccine against drug-resista... (/departments/genetics/ target

Einstein awarded $6 million grant to develop new TB vaccine against drug-resistant strains

Date:5/31/2012

/departments/genetics/" target="_blank">genetics at Einstein and a Howard Hughes Medical Institute investigator, who led the development of the new vaccine approach and is principal investigator of the NIH grant.

Einstein's vaccine approach emerged from basic studies of how TB bacteria outwit the immune system. Dr. Jacobs and his colleagues worked with M. smegmatis, which in high doses is lethal in mice but does not harm humans. The researchers created a version of M. smegmatis lacking a set of genes, known as ESX-3, considered crucial for evading host immunity. When high doses of the altered bacteria were infused into mice, it became clear that bacteria lacking the ESX-3 genes could no longer evade their hosts' immune system: the mice controlled and cleared the infection through a robust T-cell response the same response a successful TB vaccine would elicit.

Unfortunately, Dr. Jacobs found that removing the same set of genes from M. tuberculosis killed the bacterium which meant M. tuberculosis could not be manipulated in this way to make a vaccine. But Dr. Jacobs and his colleagues found a way around this stumbling block. They took the M. smegmatis bacteria lacking ESX-3 and inserted the analogous set of M. tuberculosis ESX-3 genes. These M. smegmatis bacteria were then infused into mice, which once again fought off the infection. And eight weeks later, when the mice were challenged with high doses of M. tuberculosis which kills mice as well as people these "vaccinated" mice lived much longer than control mice: an average survival time of 135 days vs. 54 days.

Of particular note was the markedly reduced level of TB bacteria found in the animals' tissues. "Most notably," said Dr. Jacobs, "those vaccinated animals that survived for more than 200 days had livers that were completely clear of TB bacteria, and nobody has ever seen that before." Only about one
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Contact: Kim Newman
sciencenews@einstein.yu.edu
718-430-3101
Albert Einstein College of Medicine
Source:Eurekalert

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