New Strep A human problem mannequin paves the way in which to check vaccines in opposition to the lethal micro organism

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New Strep A human challenge model paves the way to test vaccines against the deadly bacteria

A scanning electron microscope image of Group A streptococci (orange) during phagocytic interaction with a human neutrophil (blue). Image Credit: NIAID

Researchers have successfully developed a new human Strep A challenge model that can be used to test vaccines against the common deadly bacteria that cause sore throats, scarlet fever and skin sores.

Collaborative research, led by Murdoch Children's Research Institute (MCRI) and published in The Lancet Microbe, found that the model used to intentionally infect healthy adult volunteers with the bacteria in a controlled environment was safe and now up for trial should be used by strep A candidate vaccines.

Strep A infections affect around 750 million people and kill more than 500,000 people worldwide each year – more than influenza, typhoid or whooping cough. Strep A can also cause serious life-threatening infections such as toxic shock syndrome and carnivorous diseases, as well as post-infectious diseases such as acute rheumatic fever, rheumatic heart disease, and kidney disease.

Strep A infections disproportionately affect young children, the elderly, pregnant women and indigenous Australians. No vaccine is currently available to prevent Strep A and may only be treated with antibiotics.

Dr. MCRI's Josh Osowicki said given that Strep A are only naturally infected people, researchers were limited in what they could learn in the laboratory and using animal models.

"Human challenge models can be used to test vaccines, drugs and diagnostic tests and to drive all sorts of wonderful scientific collaborations to understand more about how diseases work and how to stop them," he said.

"We have developed the only current Strep A-controlled human infection model that can be used as a platform for evaluating new vaccine candidates and therapeutics."

Dr. Osowicki said the research team tested a strain of Strep-A that they believed would cause a sore throat and is unlikely to cause acute or chronic health problems.

The study enrolled 25 volunteers, ages 18 to 40, who stayed for up to six days at Nucleus Network, a Melbourne-based phase 1 clinical trial division, who regularly collected blood tests, saliva and throat swabs.

Dr. Osowicki said 85 percent of the participants had developed a compelling case of strep throat, well above the expected at least 60 percent.

"Starting at a tenth the dose used in old studies from the 1970s, we put our special Strep A strain on each participant's throat," he said. "To our surprise, our exposure to the low starting dose caused sore throats in most of the participants from the first participant."

The volunteers developed mild to moderate symptoms such as a sore throat, sweating, fever, and headache. All recovered quickly and were followed up for six months after the study after they were sent home.

Tania O & # 39; Meara's Melbourne daughter Eden was only 11 months old when she nearly lost her leg to a carnivorous bacterial infection from Strep A.

"We put our daughter to bed with a cold, but the next morning she woke up with a fever and was very pale, limp and dehydrated," she said.

"We took her to the hospital, but the doctor couldn't get the IV because Eden was so dehydrated and they had to dig it into her leg. They also noticed that the skin on her leg was a different color."

Ms. O & # 39; Meara said Eden needed an operation on her right calf to remove the dead flesh.

"We were told she might die and we got ready so it was a miracle they could save her leg and even her calf muscle," she said.

Eden, now three, needed three more surgeries and has since made a full recovery.

Ms O & # 39; Meara said she was relieved that a vaccine for Step A might not be too far away.

"I don't want any other family to know what we've been through. It's an absolute tragedy that this bacterium is shortening so many lives," she said.

MCRI professor Andrew Steer said the team is expected to begin testing Strep A vaccine candidates developed by researchers in Australia and overseas before the end of the year.

The trials to be carried out in Melbourne would involve around 50 participants who would receive a vaccine candidate or placebo and have the Strep A-Challenge strain applied to their necks.

"The global exposure to Strep A is an unmet public health challenge. We hope this research will accelerate vaccine development and lead things to larger field trials," said Professor Steer.

"A vaccine against Strep A will save hundreds of thousands of lives each year and prevent millions of infections that send children and adults to hospitals and doctors."

Is it a sore throat or a sore throat?

More information:
Joshua Osowicki et al., A Controlled Human Infection Model of Streptococcus Pyogenes Pharyngitis (CHIVAS-M75): An Observational Dose Finding Study, The Lancet Microbe (2021). DOI: 10.1016 / S2666-5247 (20) 30240-8

Provided by
Murdoch Children's Research Institute

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