Corporate Banner
Satellite Banner
Biologics & Bioprocessing
Scientific Community
Become a Member | Sign in
Home>News>This Article

Experimental Vaccine Shows Promise against TB Meningitis

Published: Tuesday, June 18, 2013
Last Updated: Tuesday, June 18, 2013
Bookmark and Share
Study in animals lays groundwork for new prevention strategies in brain TB.

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.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Scientific News
"Good" Mozzie Virus Might Hold Key to Fighting Human Disease
Australian scientists have discovered a new virus carried by one of the country’s most common pest mosquitoes.
World’s First Therapeutic Venom Database
Open-source library describes nearly 43,000 effects on the human body.
Speeding Up the Process of Making Vaccines
System uses a freeze-dry concept to develop "just-add-water" solution.
Surprising Trait Found in Anti-HIV Antibodies
Scientists at The Scripps Research Institute (TSRI) have new weapons in the fight against HIV.
New Method Identifies Up to Twice as Many Proteins and Peptides
An international team of researchers developed a method that identifies up to twice as many proteins and peptides in mass spectrometry data than conventional approaches.
The Do’s and Don’ts of SPR Experiments
Surface Plasmon Resonance (SPR) is a technique that is becoming more widely used, particularly by anyone who wants to obtain accurate on (association) and off (dissociation) rates for biomolecular binding.
Genetically Engineering Algae to Kill Cancer Cells
New interdisciplinary research has revealed the frontline role tiny algae could play in the battle against cancer, through the innovative use of nanotechnology.
Novel Stem Cell Line Avoids Risk of Introducing Transplanted Tumors
Progenitor cells might eventually be used to repair or rebuild damaged or destroyed organs.
Single Vaccine for Chikungunya, Related Viruses May be Possible
What if a single vaccine could protect people from infection by many different viruses? That concept is a step closer to reality.
Blocking the Transmission Of Malaria Parasites
Vaccine candidate administered for the first time in humans in a phase I clinical trial led by Oxford University’s Jenner Institute, with partners Imaxio and GSK.

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos