Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A key step toward a safer strep vaccine

12.06.2014

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.


This is an electron micrograph, in false color, of group A Streptococcus bacteria.

Credit: UC San Diego School of Medicine

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."

... more about:
»Health »genes

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.

###

Co-authors include Kirsten Kuipers, Anna Henningham, Ana Kasirer-Friede, Leo Lin, Samira Dahesh, Laura Shaw, Jennifer Gin, Sanford Shattil and Biswa Choudhury, UC San Diego; Ramy Aziz, Cairo University, Egypt; Evelien Berends and Suzan Rooijakkers, Utrecht University, Netherlands; Mark Davies and Gordon Dougan, Wellcome Trust Sanger Institute, United Kingdom; Fan Zhang and Richard Malley, Boston Children's Hospital; Madeleine Cunningham, University of Oklahoma; Joseph Merriman and Patrick Schlievert, University of Iowa; Julia Hüttner and Bernd Lepenies, Max Planck Institute of Colloids and Interfaces, Germany; and Mark Walker, University of Queensland, Australia.

This study was funded, in part, by the National Institutes of Health, including the UC San Diego Program in Excellence in Glycosciences, the Australian National Health and Medical Research Council, the Wellcome Trust, and the Netherlands Organization for Scientific Research.

Scott LaFee | Eurek Alert!

Further reports about: Health genes

More articles from Life Sciences:

nachricht Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>