Researchers have discovered how antibodies help to protect against contagious bacterial infections caused by Strep A, including strep throat. And the findings are already contributing to efforts to accelerate the development of a Strep A vaccine.
The research, led by Murdoch Children’s Research Institute (MCRI), Monash University and the University of Auckland, using the world’s only human challenge model for Strep A, has uncovered how antibodies respond to strep throat infections.
MCRI Dr Joshua Osowicki said the research showed the power and potential for the human model to help crack the secrets of Strep A and accelerate vaccine development.
The findings, published in Nature Communications, closely looked at antibodies produced against different parts of Strep A bacteria, comparing blood and saliva results before and after the Strep A challenge. The challenge involved 25 healthy adults in Melbourne who were exposed to a low level of Strep A bacteria in a controlled environment.
“With Strep A being extremely common and every healthy adult having previously encountered it, all the participants had some antibodies against Strep A before the study,” Dr Osowicki said.
“We found each person’s pre-existing antibodies made a difference to what happened when they were exposed during the challenge. For some of the participants, the mixture of antibodies before the challenge helped to protect them from developing a strep throat infection. Even in those who did develop strep throat, with symptoms like a sore throat and fever, it was clear their pre-existing antibodies made a difference to clinical outcomes.”
Importantly, the response to Strep A in the participants resembled those seen in children who will be first in line for a Strep A vaccine.
Dr Osowicki said developing an effective vaccine had been difficult as there were big gaps in our understanding into how humans were protected against Strep A infections.
“The bulk of Strep A research has used animal models but only humans are naturally infected by Strep A,” he said. This research helps vaccine developers to answer that key question and proves that we can use our human model to test promising vaccine candidates and explore how they work.”
The findings come as Dr Osowicki and his team were awarded a $10 million grant from Wellcome for more research using the Strep A human challenge model to accelerate vaccine development.
Under the grant, Dr Osowicki, alongside MCRI colleagues Dr Hannah Frost and Professor Andrew Steer, will lead an international consortium spanning six institutes across Australia, The Gambia, the UK and New Zealand. The research partners include Monash University, Medical Research Council Unit The Gambia, London School of Hygiene & Tropical Medicine, University of New South Wales (Kirby Institute), University of Auckland, and University of Sheffield. The project will also involve major international vaccine developers as part of an advisory group.
Wellcome, a UK-based independent charitable foundation, supports innovative projects to help solve the world’s most pressing health challenges, including infectious diseases.
The project will use the MCRI team’s Strep A human challenge model in trial participants in Australia and The Gambia to test different ideas about which kinds of immune responses stop people from getting Strep A infections. A vaccine that can produce similar responses should prevent infections across the whole Strep A disease spectrum.
Strep A infections affect about 750 million people and kill more than 500,000 globally every year, more than influenza, typhoid or whooping cough. Strep A can also cause severe life-threatening infections like toxic shock syndrome, flesh eating disease and post-infectious illnesses such as acute rheumatic fever, rheumatic heart disease and kidney disease.
Strep A vaccine research is one response to the World Health Organization’s (WHO) resolution for a global, coordinated response into rheumatic fever and rheumatic heart disease.
Dr Frost said by developing the world’s only Strep A human challenge model, our team had changed the vaccine development landscape.
“With this funding from Wellcome, we will answer some of the biggest and most stubborn questions that are standing in the way of developing, licensing and implementing a successful Strep A vaccine,” she said.
“While this was traditionally a long and difficult process, bringing world experts and industry partners together would fast-track efforts to address the unmet global public health need for a safe and effective Strep A vaccine.”
Professor Steer said the project could help prevent Strep A related illness and death around the world.
“There is a huge need for the development of a vaccine to reduce the burden of Strep A disease and we are proud to lead this work out of MCRI,” he said. Another major benefit of this vaccine would be the reduction of rheumatic heart disease rates globally, a preventable illness that has been identified as a global priority.”
about MCRI’s work in Strep A research and vaccine development, including with the Australian Strep A Vaccine Initiative (ASAVI) co-led with The Kids Research Institute Australia and the Strep A Vaccine Global Consortium (SAVAC).
Publication: Joshua Osowicki, Hannah R Frost, Kristy I Azzopardi, Alana L Whitcombe, Reuben McGregor, Lauren H. Carlton, Ciara Baker, Loraine Fabri, Manisha Pandey, Michael F Good, Jonathan R. Carapetis, Mark J Walker, Pierre R Smeesters, Paul V Licciardi, Nicole J Moreland, Danika L Hill and Andrew C Steer. ‘Streptococcus pyogenes pharyngitis elicits diverse antibody responses to key vaccine antigens influenced by the imprint of past infections,' Nature Communications. DOI: 10.1038/s41467-024-54665-5
*The content of this communication is the sole responsibility of MCRI and does not reflect the views of the NHMRC.
Available for interview:
Dr Hannah Frost, MCRI researcher, Tropical Diseases
Dr Joshua Osowicki, MCRI Team Leader, Tropical Diseases
Professor Andrew Steer, MCRI Theme Director, Infection, Immunity and Global Health
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