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!
Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University
New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).
Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
16.02.2018 | Information Technology
16.02.2018 | Health and Medicine
16.02.2018 | Physics and Astronomy