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!
Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care
Disrupted fat breakdown in the brain makes mice dumb
19.05.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.
Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...
22.05.2017 | Event News
17.05.2017 | Event News
16.05.2017 | Event News
22.05.2017 | Materials Sciences
22.05.2017 | Life Sciences
22.05.2017 | Physics and Astronomy