Gene-Encoding Molecule Offers Clues Towards Safer Strep Vaccine

Researchers at the University of California, San Diego School of Medicine may have developed a safe and effective vaccine against strep throat, according to a study published in the journal Cell Host & Microbe. 

The study authors identified the genes encoding a molecule that defines Group A Streptococcus (strep), also known as a pathogenic bacterial species that's responsible for  over 700 million infections each year worldwide.

"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, in a news release. "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."

As some patients with the infections develop antibodies that cross-react with their own heart valve tissues, which may result in rheumatic fever or even heart damage, developing such a vaccine has been difficult. Rheumatic fever, though relatively rare in the United States, is still an issue in some developing countries.

Researchers discovered that the cell wall of strep, which is composed primarily of a single molecule called group A carbohydrate (or GAC), is built from repeating units of bacterial sugar rhamnose, as well as the human-like sugar N-acetylglucosamine (GlcNAc).

Previous studies have suggested that GLcNAc sugars present in GAC may be responsible for triggering production of heart-damaging antibodies found in some patients.

"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."

Lastly, researchers determined a way to remove the GLcNAc sugar so that a mutant form of the bacteria with only rhamnose-containing GAC could be purified and tested as an antigen for the vaccine.

"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."