According to the World Health Organization, TB kills an estimated 1.7 million people each year and infects one out of three people around the globe. With drug-resistant strains spreading, a vaccine for preventing TB is urgently needed.
"Producing effective TB vaccines requires a better understanding of the mechanisms used by Mycobacterium tuberculosis [the bacterial species that causes TB] to evade the body's immune responses," said senior author William Jacobs, Jr., Ph.D., professor of microbiology & immunology and of genetics at Einstein and a Howard Hughes Medical Institute investigator. He notes that the only currently used vaccine, the Bacille Calmette-Gu¨¦rin (BCG) vaccine, has been notoriously inconsistent in protecting against TB.
To determine how M. tuberculosis outwits the immune response, Dr. Jacobs and his colleagues worked with a closely related species known as Mycobacterium smegmatis that is lethal to mice at high doses but does not harm people. 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-3genes could no longer evade their hosts' immune system: the mice controlled and cleared the infection through a robust T-cell response¡ªthe 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¡ªwhich kills mice as well as people¡ªthese "vaccinated" mice lived much longer than control mice: an average survival time of 135 days vs. 54 days.
Just as impressive, said Dr. Jacobs, was the markedly reduced level of TB bacteria found in the animals' tissues. "Most notably," he said, "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."
Dr. Jacobs cautioned that only about one in five mice showed this robust response¡ªindicating that the vaccine must be improved before it can be considered sufficiently effective. "We don't even know yet if it will work in humans, but it's certainly a significant step in efforts to create a better TB vaccine," he said.
Aeras, a Rockville, MD-based non-profit development partnership dedicated to preventing TB, has licensed the technology described in this study and is using it to develop a new TB vaccine. The technology could also provide the basis for vaccines that eliminate leprosy and other virulent mycobacteria from infected tissues.
The group's paper is titled "A recombinant Mycobacterium smegmatis induces potent bactericidal immunity against M. tuberculosis." Other Einstein researchers involved in the study were lead author Kari Sweeney, Ph.D.; Dee Dao, Ph.D.; Michael Goldberg, M.S.; Tsungda Hsu, Ph.D.; Manjunatha Venkataswamy, Ph.D.; Rani Sellers, Ph.D., DVM; Paras Jain, Ph.D.; Bing Chen, M.D.; Mei Chen; John Kim, Regy Lukose, John Chan, M.D.; and Steven Porcelli, M.D.. Diane Ordway, Ph.D., and Ian Orme, Ph.D., of Colorado State University, Fort Collins, CO were also co-authors of the study. The research was funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Dr. Jacobs' research is also funded by the Howard Hughes Medical Institute.
Albert Einstein College of Medicine
Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. In 2010, Einstein received nearly $200 million in support from the NIH for major research centers at Einstein in diabetes, cancer, liver disease, and AIDS, as well as other areas. Through its extensive affiliation network with five medical centers, Einstein runs one of the largest post-graduate medical training programs in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training. For more information, please visit www.einstein.yu.edu
Kim Newman | EurekAlert!
New study points the way to therapy for rare cancer that targets the young
22.11.2017 | Rockefeller University
Penn study identifies new malaria parasites in wild bonobos
21.11.2017 | University of Pennsylvania School of Medicine
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
23.11.2017 | Information Technology
23.11.2017 | Physics and Astronomy
23.11.2017 | Life Sciences