A team of Johns Hopkins researchers working with animals has developed a vaccine that prevents the virulent TB bacterium from invading the brain and causing the highly lethal condition TB meningitis, a disease that disproportionately occurs in TB-infected children and in adults with compromised immune system.
A report on the federally funded research is published online June 11 in the journal PLOS ONE.
TB brain infections often cause serious brain damage and death even when recognized and treated promptly, researchers say. This is so because many drugs currently used to treat resistant TB strains cannot cross the so-called brain-blood barrier, which stops pathogens from entering the brain, but also keeps most medicines woefully out of the brain's reach.
"Once TB infects the brain, our treatment options have modest effect at best, so preventing brain infection in the first place is the only fool-proof way to avert neurologic damage and death," said lead investigator Sanjay Jain, M.D., an infectious disease specialist at the Johns Hopkins Children's Center. "Unfortunately, our sole preventive weapon, the traditional BCG vaccine, has a spotty track record in terms of efficacy."
The new Johns Hopkins vaccine, tested in guinea pigs, could eventually add a much-needed weapon to a largely depleted therapeutic and preventive arsenal. TB currently affects nearly 9 million people worldwide and is growing increasingly resistant to many powerful antibiotics, according to the World Health Organization (WHO).
The experimental vaccine works against certain lethal strains of TB that are marked by the presence of a protein known as PknD, which helps the TB bacterium sneak past the blood-brain barrier. Specifically, PknD makes TB virulent by allowing it to attach to, damage and penetrate the protective cells that line the small blood vessels of the brain and prevent toxins and bugs traversing the blood from invading the organ.
If proven effective in people, the vaccine also could be used to boost the brain-protective effects of the traditional BCG vaccine, the only currently available anti-TB vaccine, the efficacy of which varies greatly, Jain says. In addition, BCG contains live bacteria and therefore cannot be given to immune-compromised people, such as HIV patients, who are at greater risk of developing widespread TB. About one-third of the 34 million HIV-infected people worldwide have TB, according to the WHO.
By contrast, the experimental vaccine is made with PknD protein chunks, which by themselves cannot cause full-blown disease even in people with weakened immune systems.
In their experiments, the Johns Hopkins researchers compared the effectiveness of the new vaccine with the traditional BCG vaccine. Animals were injected with placebo, BCG or the new vaccine and then exposed to airborne TB. The researchers measured TB loads in the lungs and brains of all three groups, as well as in those of non-vaccinated animals.
Animals given either active vaccine had far fewer TB cells in their brains compared with their non-vaccinated or placebo-vaccinated counterparts. Both vaccines were equally effective in preventing invasive TB infections of the brain and spinal cord, even though the new vaccine fared worse at reducing TB cell loads in the lungs. Notably, animals injected with the new vaccine had TB cell counts in their lungs similar to those of placebo-injected or non-vaccinated animals, yet far fewer TB cells in their brains.
"What this tells us is that even in the presence of full-blown lung infection, the new vaccine somehow blunted TB's ability to infect and damage the brain," said investigator Ciaran Skerry, Ph.D., of the Johns Hopkins Center for Tuberculosis Research.
Animals that got the new vaccine also had higher levels of protective TB-specific antibodies and higher levels of interferons, the cry-for-help chemicals released by virus-infected or bacterium-infected cells that summon the body's immune defenses against pathogens.
To determine whether the new vaccine could also render the TB bacterium less virulent in human cells, the researchers soaked TB bacteria in blood obtained from BCG-vaccinated, non-vaccinated and experimentally vaccinated animals, then mixed the pre-soaked TB bacteria with human endothelial cells that line the small blood vessels of the brain and guard it against invasive pathogens. Bacteria treated with blood from the experimentally vaccinated animals showed far less virulence and were far less capable of damaging the human cells than were the TB bacteria soaked in blood from BCG-vaccinated or non-vaccinated animals.
The study was funded by the National Institutes of Health under grants OD006492 and AI083125.
Co-investigators included Supriya Pokkali, Michael Pinn, Nicholas Be, Jamie Harper and Petros Karakousis, all of Johns Hopkins.
Related on the Web:
TB Treatment Paradox: Mouse Studies Show Body's Own Response Helps TB Bacteria Survive http://www.hopkinschildrens.org/Mouse-Studies-Show-Bodys-Own-Response-Helps-Tb-Bacteria-Survive.aspx
Hopkins Children's Researcher Wins NIH Innovator Award for TB Work http://www.hopkinschildrens.org/newsDetail.aspx?id=7118Founded in 1912 as the children's hospital of the Johns Hopkins Medical Institutions, the Johns Hopkins Children's Center offers one of the most comprehensive pediatric medical programs in the country, with more than 92,000 patient visits and nearly 9,000 admissions each year. Hopkins Children's is consistently ranked among the top children's hospitals in the nation. Hopkins Children's is Maryland's largest children's hospital and the only state-designated Trauma Service and Burn Unit for pediatric patients. It has recognized Centers of Excellence in dozens of pediatric subspecialties, including allergy, cardiology, cystic fibrosis, gastroenterology, nephrology, neurology, neurosurgery, oncology, pulmonary, and transplant. For more information, visit http://www.hopkinschildrens.org.
Helen Jones, firstname.lastname@example.org, (410) 502-9422 June 11, 2013
Ekaterina Pesheva | EurekAlert!
New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)
Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences