Developing a Vaccine to Prevent Streptococcal Toxic Syndrome

A vaccine prevented Streptococcal toxic syndrome (STSS) in transgenic mice, paving the way for a humanized version of a vaccine against this infection, according to a report published in Science Advances.

Invasive streptococcal disease (ISD), which can turn into STSS, causes more than 160,000 deaths annually. The disease is easily spread by coughing, sneezing, and sharing food and drinks.

Investigators from Griffith University in Australia gave mice a version of this infection in order to determine what vaccination methods might be viable. They understood that J8 is a vaccination candidate based on the M protein, and in mice, it protects from skin, mucosal, and intraperitoneal streptococcal infections. In humans, J8 is undergoing further research in clinical trials.

Originally, the researchers had been looking at a vaccine candidate to prevent rheumatic heart disease, which is also caused by streptococcal infections. The investigators later adjusted their thinking and realized the vaccine could also work to prevent STSS, they

Dr. Manisha Pandey

said.

“Our lead vaccine candidate J8 is able to prevent S pyogenes infections and therefore it was assumed that the protection would extend to protection against STSS,” lead researcher Dr Manisha Pandey explained to Contagion®. “However, we were very surprised to see that passive immunotherapy with J8 antibodies would resolve established disease completely. We found that J8 antibodies, with or with anti-toxin antibodies, could quickly eliminate virtually the entire systemic bacterial load and resolve the clinical score.”

Using antibodies the mice developed from the streptococcal M protein and S pyogenes, the investigators cleared the mice of infection. They also removed the damage and inflammatory activity caused by the M protein. When treated with the vaccine antibodies, the mice recovered overnight, the investigators observed. Both the infectious organisms and the toxins in their blood were cleared after vaccination treatment, they said.

The investigators also uncovered another novel finding: that streptococcal M-protein and the superantigen toxin are involved in STSS pathogenesis. Additionally, they learned that blocking either will, in turn, block the disease.

“The finding that immunotherapy with J8 antibodies would lead to not only bacterial clearance, but would also block the mitogenic activity of M-protein which would ultimately prevent STSS like pathology is very encouraging,” Pandey said.

While this vaccination is believed to prevent the disease, a person without the inoculation suffering from STSS will need immediate interventions, Pandey added.

“That’s where passive immunotherapy with vaccine induced antibodies will be critical,” she said. “Currently STSS is treated with antibiotics and intravenous immunoglobulin with limited success… The use of J8 antibodies in the treatment of STSS will specifically target the causative organism and will block its pathogenic mechanisms that lead to STSS. This will significantly improve the treatment outcome and survival rates in STSS patients.”

The investigators are now testing the vaccine in the treatment in humanized mouse models that can mimic the human STSS pathology. Pandey called their preliminary results “quite promising,” and said that they are “optimistic that humanized monoclonal will be available in the next 2 years to undergo clinical trial in humans.”