Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

A Key Step Toward a Safer Strep Vaccine

Published: Friday, June 13, 2014
Last Updated: Friday, June 13, 2014
Bookmark and Share
Gene discovery identifies molecular pathway to potential preventive treatment.

An international team of scientists, led by researchers at the University of California, San Diego School of Medicine, have identified the genes encoding a molecule that famously defines Group A Streptococcus (strep), a pathogenic bacterial species responsible for more than 700 million infections worldwide each year.

The findings, published online in the June 11 issue of Cell Host & Microbe, shed new light on how strep bacteria resists the human immune system and provides a new strategy for developing a safe and broadly effective vaccine against strep throat, necrotizing fasciitis (flesh-eating disease) and rheumatic heart disease.

“Most people experience one or more painful strep throat infections as a child or young adult,” said senior author Victor Nizet, MD, professor of pediatrics and pharmacy. “Developing a broadly effective and safe strep vaccine could prevent this suffering and reduce lost time and productivity at school and work, estimated to cost $2 billion annually.”

Efforts to develop such a vaccine have been significantly hindered by complexities in how the human immune system reacts to the bacterial pathogen. Specifically, some patients with strep infections produce antibodies that cross-react with their own heart valve tissue, leading to rheumatic fever and heart damage. Though rare in the United States, rheumatic fever remains common in some developing countries and causes significant disability and death.

The Cell Host & Microbe study suggests a way to circumvent the damaging autoimmune response triggered by strep. Specifically, the researchers noted that the cell wall of strep is composed primarily of a single molecule known as the group A carbohydrate (or GAC) which, in turn, is built from repeating units of the bacterial sugar rhamnose and the human-like sugar N-acetylglucosamine (GlcNAc).

Previous research has indicated that GlcNAc sugars present in GAC may be responsible for triggering production of heart-damaging antibodies in some patients. Nizet said the latest findings corroborate this model, and suggest that eliminating the pathogen’s ability to add GlcNAc sugars to GAC could be the basis for a safe vaccine.

“In this study, we discovered the strep genes responsible for the biosynthesis and assembly of GAC, the very molecule that defines the pathogen in clinical diagnosis,” said first author Nina van Sorge, PharmD, PhD, a former postdoctoral fellow at UC San Diego who now leads her own laboratory at Utrecht University Medical Center in the Netherlands. “This discovery allowed us to generate mutant bacterial strains and study the contribution of GAC to strep disease.”

The researchers found that a mutant strep strain lacking the human-like GlcNAc sugar on the GAC molecule exhibited normal bacterial growth and expressed key proteins known to be associated with strep virulence, but was easily killed when exposed to human white blood cells or serum. The mutant strep bacteria also lost the ability to produce severe disease in animal infection models.

“Our studies showed that the GlcNAc sugar of GAC is a critical virulence factor allowing strep to spread in the blood and tissues,” van Sorge said. “This is likely important for the rare, but deadly, complications of strep infection such as pneumonia, necrotizing fasciitis and toxic shock syndrome.”

The researchers also identified a way to remove the problematic GlcNAc sugar so that a mutant form of the bacteria with only rhamnose-containing GAC could be purified and tested as a vaccine antigen.

“We showed that antibodies produced against mutant GAC antigen helped human white blood cells kill the pathogen and protected mice from lethal strep infection,” said Jason Cole, PhD, a visiting project scientist from the University of Queensland, Australia, and co-lead author of the paper. “Because GAC is present in all strep strains, this may represent a safer antigen for inclusion in a universal strep vaccine.”

Researchers plan to assess the new modified antigen against other candidates in advanced strep throat vaccine tests in nonhuman primates beginning later this year in Atlanta, Georgia, funded by the National Health and Medical Research Council of Australia.

“It is satisfying to find that a fundamental observation regarding the genetics and biochemistry of the pathogen can have implications not only for strep disease pathogenesis, but also for vaccine design,” Nizet said.


Further Information

Join For Free

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 3,300+ scientific posters on ePosters
  • More Than 4,900+ 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 TechnologyNetworks.com 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.

Related Content

Drug - Gene 'One-Two' Punch Against Cancer
Researchers identify gene-drug combinations that, together, target and kill cancer cells while not targeting healthy cells.
Friday, July 22, 2016
Complex Mouse Behaviours Linked to the Genes that Influence Them
Two novel genes were associated with methamphetamine sensitivity and anxiety-like behavior.
Wednesday, July 06, 2016
HIV Modification May Put a Twist on Vaccine and Drug Design
Crucial HIV RNA modification called m6A influences viral replication, but wasn’t previously taken into consideration when developing anti-HIV therapies.
Wednesday, February 24, 2016
Novel Stem Cell Line Avoids Risk of Introducing Transplanted Tumors
Progenitor cells might eventually be used to repair or rebuild damaged or destroyed organs.
Thursday, November 12, 2015
Gel Filled with Nanosponges Cleans up MRSA Infections
Nanosponge-hydrogel minimize the growth of skin lesions on MRSA infected mice without the use of antibiotics.
Thursday, May 21, 2015
Multiple Models Reveal New Genetic Links in Autism
For answers, researchers turned to mice, stem cells and the “tooth fairy”.
Tuesday, November 11, 2014
Novel Drug Targeting Leukemia Cells Enters Clinical Trial
Phase 1 human clinical trial to assess the safety and efficacy of a new monoclonal antibody for CLL patients.
Friday, September 19, 2014
Scientists Discover Neurochemical Imbalance in Schizophrenia
Researchers discovers that neurons from schizophrenia patients secrete higher amounts of three neurotransmitters.
Tuesday, September 16, 2014
Clinical Trial to Test Safety of Stem Cell-Derived Therapy for Type 1 Diabetes
UC San Diego is initial site for first-in-human testing of implanted cell therapy.
Wednesday, September 10, 2014
Clinical Trial Evaluates Safety of Stem Cell Transplantation in Spine
Phase I clinical trial is recruiting eight patients for the 5-year study.
Wednesday, August 13, 2014
Dramatic Growth of Grafted Stem Cells in Rat Spinal Cord Injuries
Reprogrammed human neurons extend axons almost entire length of central nervous system.
Tuesday, August 12, 2014
Epigenetics Alters Genes in Rheumatoid Arthritis
Researchers investigate how henetic changes, other than DNA mutations, play a part in susceptibility to the onset of disease.
Friday, July 06, 2012
Clarity Begins at Exome
Sequencing protein-making part of genome can change diagnosis and patient care.
Friday, June 15, 2012
Hormone Plays Surprise Role in Fighting Skin Infections
Previously associated with calcium homeostasis, hormone now found to hold critical role in boosting AMP expression.
Friday, May 25, 2012
Scientific News
Shedding Light on HIV Vaccine Design
Broadly speaking - Mathematical modelling of host-pathogen coevolution sheds light on HIV vaccine design.
AACC 2016 Sees Clinical Chemistry Labs Drive Precision Medicine Offerings
Biomarker assays to enable precision medicine and risk assessment, mass spec-based tests designed for use in clinical labs large and small, and liquid biopsy technology captured the spotlight at the AACC annual meeting.
Automated Patch Clamping Trends
Learn more about current practices, preferences and metrics in ion channel drug screening using APC technology.
Emerging Model of Cancer
Cancer acts cooperatively, making individual decisions but acting in unison; this insight is being used to create a computer model of cancer.
Biological Barcodes Using CRISPR
Using genome editing tools, researchers are getting closer to understand differentiation of various cell types during development.
Controlling DNA Repair
Scientists discover that DNA repair outcomes following CRISPR-Cas9 cleaving are non-random and can be harnessed to produce desired effects.
Demonstrating LNP Delivery of CRISPR Components
Intellia has presented data demonstrating in vivo gene editing ising liquid nanoparticles (LNPs) to deliver CRISPR/Cas9.
Decades Old Chemicals Linked to Current Increased Autism Risk
The chemcials - organochlorines - were banned in the US in 1977 but their side effects are still being seen.
FINCH Filgotinib Phase 3 Program Initiated
Galapagos NV reports the initiation of the FINCH global Phase 3 program in rheumatoid arthritis patient populations.
Enzyme that Triggers Cell Demise in ALS Identified
Scientists from Harvard have identified a key instigator of nerve cell damage in people with amyotrophic lateral sclerosis (ALS).
Scroll Up
Scroll Down
Skyscraper Banner

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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!