UCLA-led research finds that a variant of an existing vaccine offers stronger protection against both diseases
In many parts of the world, leprosy and tuberculosis live side-by-side. Worldwide there are approximately 233,000 new cases of leprosy per year, with nearly all of them occurring where tuberculosis is endemic.
The currently available century-old vaccine Bacille Calmette-Guerin, or BCG, provides only partial protection against both tuberculosis and leprosy, so a more potent vaccine is needed to combat both diseases. UCLA-led research may have found a stronger weapon against both diseases.
In a study published in the September issue of the peer-reviewed journal Infection and Immunity, the researchers found that rBCG30, a recombinant variant of BCG that overexpresses a highly abundant 30 kDa protein of the tuberculosis bacterium known as Antigen 85B, is superior to BCG in protecting against tuberculosis in animal models, and also cross protects against leprosy. In addition, they found that boosting rBCG30 with the Antigen 85B protein, a protein also expressed by the leprosy bacillus, provides considerably stronger protection against leprosy.
"This is the first study demonstrating that an improved vaccine against tuberculosis also offers cross-protection against Mycobacterium leprae, the causative agent of leprosy," said Dr. Marcus A. Horwitz, professor of medicine and microbiology, immunology and molecular genetics, and the study's senior author. "That means that this vaccine has promise for better protecting against both major diseases at the same time.
"It is also the first study demonstrating that boosting a recombinant BCG vaccine further improves cross-protection against leprosy," he added.
In one experiment, mice were immunized with either rBCG30 or the old BCG vaccine, or they were given a salt solution. Ten weeks later, the mice were injected with live leprosy bacteria into their footpads and seven months after that, the number of leprosy bacteria in their footpads was measured. The researchers found that the mice given BCG or rBCG30 had much fewer leprosy bacteria in their footpads than the mice given the salt solution. Additionally, mice immunized with rBCG30 had significantly fewer leprosy bacteria than those vaccinated with BCG.
In a second experiment, the mice were first immunized with BCG or rBCG30, and then immunized with a booster vaccine (r30) consisting of the TB bacterium's 30-kDa Antigen 85B protein in adjuvant — that is, in a chemical formulation that enhances the immune response. The group of mice immunized with rBCG30 and boosted with r30 had no detectable leprosy bacteria in their footpads, in contrast to groups of mice immunized with all other vaccines tested, including BCG and rBCG30 alone and BCG boosted with r30.
In other experiments, the immune responses of the mice were measured after vaccination. Mice immunized with rBCG30 and boosted with r30 had markedly enhanced immune responses to the leprosy bacterium's version of the Antigen 85B protein, which is very similar to the one expressed by the tuberculosis bacillus, compared with mice immunized with the other vaccines and vaccine combinations.
A Phase 1 human trial for rBCG30 has proven that it is safe and significantly more effective than BCG, and it is the only candidate replacement vaccine for BCG tested thus far to satisfy both of these key clinical criteria. Horwitz noted that this most recent study, however, was conducted in an animal model of leprosy, so further study is needed to gauge the effectiveness of the rBCG30 vaccine in protecting against leprosy in humans.
The next step in the research will be to test the rBCG30 vaccine for efficacy in humans against TB. If it's effective against TB, then the next step would be to test its effectiveness in humans against leprosy.
The study's co-authors are Thomas Gillis of Louisiana State University and Michael Tullius of UCLA.
Grants from the National Institutes of Health (AI031338) and the National Hansen's Disease Programs funded this study. In addition, grants from UCLA's Jonsson Comprehensive Cancer Center (P30 CA016042) and the Center for AIDS Research (5P30 AI028697) supported flow cytometry studies used to measure immune responses, and the American Leprosy Missions supported the nude mouse colony used for the propagation of M. leprae.
Enrique Rivero | Eurek Alert!
Using DNA origami to build nanodevices of the future
31.08.2015 | Institute for Integrated Cell-Material Sciences at Kyoto University
An ounce of prevention: Research advances on 'scourge' of transplant wards
28.08.2015 | University of Wisconsin-Madison
The leaves of the lotus flower, and other natural surfaces that repel water and dirt, have been the model for many types of engineered liquid-repelling surfaces. As slippery as these surfaces are, however, tiny water droplets still stick to them. Now, Penn State researchers have developed nano/micro-textured, highly slippery surfaces able to outperform these naturally inspired coatings, particularly when the water is a vapor or tiny droplets.
Enhancing the mobility of liquid droplets on rough surfaces could improve condensation heat transfer for power-plant heat exchangers, create more efficient...
Longer, more severe, and hotter droughts and a myriad of other threats, including diseases and more extensive and severe wildfires, are threatening to transform some of the world's temperate forests, a new study published in Science has found. Without informed management, some forests could convert to shrublands or grasslands within the coming decades.
"While we have been trying to manage for resilience of 20th century conditions, we realize now that we must prepare for transformations and attempt to ease...
A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.
The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...
A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).
Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...
In mountainous regions earthquakes often cause strong landslides, which can be exacerbated by heavy rain. However, after an initial increase, the frequency of these mass wasting events, often enormous and dangerous, declines, in fact independently of meteorological events and aftershocks.
These new findings are presented by a German-Franco-Japanese team of geoscientists in the current issue of the journal Geology, under the lead of the GFZ...
20.08.2015 | Event News
20.08.2015 | Event News
19.08.2015 | Event News
01.09.2015 | Press release
01.09.2015 | Materials Sciences
01.09.2015 | Materials Sciences