Researchers from Murdoch Children's Research Institute (MCRI) successfully develops Strep A human challenge model for vaccine trials and evaluation using special strain of mild Group A Streptococcus bacterium.
2 years ago in Melbourne, 11-month-old Eden, daughter of Tania O'Meara, nearly lost her leg to a flesh-eating bacterial infection. Rushed to the hospital, Eden underwent a life-threatening surgery on her right calf to remove the dead flesh. It was not short of a miracle that Eden survived and made fully recovery. But unlike her, many others have not.
The culprit of this traumatic event is a class of bacteria most of us are well-acquainted with – Strep A. A bacterial infection, which can cause a broad spectrum of diseases ranging from mild strep throat to acute rheumatic fever, Strep A plagues 750 million people and claims more than 500,000 lives per annum, far outnumbering influenza, typhoid of the whooping cough. This potentially fatal class of bacteria is also the starting point of fatal heart and kidney diseases, and severe life-threatening infections like toxic shock syndrome and flesh-eating disease.
At present, treatment is hinged on antibiotics because there has yet to be a vaccine for Strep A. In large, the road to vaccine development has been obstructed by the limited array of animal models that can be used to test the efficacy of vaccines as Strep A only occurs naturally in humans.
Overcoming said barriers, a revolutionary breakthrough by a collaborative research done by Murdoch Children's Research Institute (MCRI) has recently developed a novel Strep A human challenge model (HCM) for the purpose of testing the efficacy of vaccines. HCM involves deliberately exposing humans to disease-causing agents in effort to test and evaluate vaccine candidates for common but lethal bacteria causing sore throats, scarlet fever and skin sores. MRCI’s HCM, currently the sole Strep A controlled human infection model, is a safe and promising framework to evaluate vaccines and therapeutics.
As stated by MCRI's Dr Josh Osowicki, "Human challenge models can be used to test vaccines, drugs and diagnostic tests, as well as driving all sorts of wonderful scientific collaborations to understand more about how diseases work and how to stop them."
Their study entailed carefully inoculating 25 healthy adult volunteers between the ages of 18 to 40 with low dosages of a specially-engineered Strep A strain on the back of their throats under controlled settings. The Strep A strain chosen was expected to cause strep throat but unlikely to induce acute or chronic health issues. Researchers collected blood tests, saliva and throat swabs regularly for 6 days from the volunteers who were also from Nucleus Network, a Melbourne-based Phase 1 clinical research organisation.
A surprising discovery made during the study was that the special Strep A strain, even at the low starting dose, had caused demonstrable cases of strep throat upon administration. The lowest starting dose was calculated to be one-tenth of the dose used in studies more than 5 decades ago.
The findings of their investigation revealed promising success, upon infection with MCRI’s Strep A strain, 85% of the participants developed a convincing case of strep throat, and developed mild to moderate symptoms such as sore throat, sweats, fever and headache. However, they all made swift recovery. The volunteers were observed for 6 months before they were sent home. As a whole, the study determined the model to be safe and applicable for trial of Strep A candidate vaccines.
With major pieces of the development puzzle finally falling into place, the Strep A vaccine is in near sight. This recent innovation of HCM is expected to accelerate vaccine progress in Australia and overseas, and vaccine trials are forecasted to begin before the end of 2021. Plans for future trials in Melbourne include infecting 50 participants with the Strep A challenge strain and inoculating candidate vaccine or placebo.
"The global burden of Strep A is an unmet public health challenge. We hope this research will accelerate the development of a vaccine and move things forward to bigger field trials," Professor Steer elaborated. "A vaccine for Strep A will save hundreds of thousands of lives every year and prevent millions of infections that send children and adults to the hospital or doctor."