Navigation Links
A key step toward a safer strep vaccine
Date:6/11/2014

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.


'/>"/>

Contact: Scott LaFee
slafee@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert  

Related medicine news :

1. Toward 24-7 glucose monitoring to help manage diabetes
2. GW Cancer Institute conducts survey on moving toward quality patient-centered care
3. Early steps toward personalized fitness: Interval training may benefit men more than women
4. Experimental trial represents promising step toward universal antidote for snakebite
5. Multimillion-dollar grant propels lab toward HIV cure
6. Toward unraveling the Alzheimers mystery
7. MSU physicists push new Parkinsons treatment toward clinical trials
8. Autism Speaks study finds advances towards universal early screening
9. Toward fixing damaged hearts through tissue engineering
10. A Priceless Resolution: Take That First Step Toward Financial Security
11. Athletes “Toward Injury Prevention in Sports” TIPS Gets Going in Las Vegas
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
A key step toward a safer strep vaccine
(Date:6/26/2016)... Lake Orion, Clarkston, Michigan (PRWEB) , ... June ... ... direction with respect to fertility once they have been diagnosed with endometriosis. These ... tolerable intercourse but they also require a comprehensive approach that can help for ...
(Date:6/25/2016)... FL (PRWEB) , ... June 25, 2016 , ... The temporary closing of Bruton Memorial ... Plant City Observer , brings up a new, often overlooked aspect of head lice: the ... closing for fumigation is not a common occurrence, but a necessary one in the event ...
(Date:6/25/2016)... ... June 25, 2016 , ... As a lifelong Southern Californian, Dr. Omkar Marathe ... from the David Geffen School of Medicine at UCLA. He trained in Internal Medicine ... his fellowship in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the ...
(Date:6/25/2016)... Montreal, Canada (PRWEB) , ... June 25, 2016 , ... ... the pursuit of success. In terms of the latter, setting the bar too high ... low, risk more than just slow progress toward their goal. , Research from ...
(Date:6/24/2016)... ... 2016 , ... June 19, 2016 is World Sickle Cell Observance Day. In ... benefits of holistic treatments, Serenity Recovery Center of Marne, Michigan, has issued ... Sickle Cell Disease (SCD) is a disorder of the red blood cells, which can ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... June 23, 2016 Roche (SIX: RO, ROG; ... for its Elecsys BRAHMS PCT (procalcitonin) assay as a ... septic shock. With this clearance, Roche is the first ... integrated solution for sepsis risk assessment and management. ... infection and PCT levels in blood can aid clinicians ...
(Date:6/23/2016)... Capricor Therapeutics, Inc. ... company focused on the discovery, development and commercialization ... in its ongoing randomized HOPE-Duchenne clinical trial (Halt ... its 24-patient target. Capricor expects the trial to ... 2016, and to report top line data from ...
(Date:6/23/2016)... -- Bracket , a leading clinical trial technology and ... platform, Bracket eCOA (SM) 6.0, at the 52 nd ... 2016 in Philadelphia , Pennsylvania.  A demonstration ... of its kind to fully integrate with RTSM, will be ... is a flexible platform for electronic clinical outcomes assessments that ...
Breaking Medicine Technology: