State-Of-The Art Techniques to Investigate Immune Response in Deadly Strep A Infections

Annually, a staggering half a million people, including numerous children and young individuals, succumb to serious infections caused by the group A streptococcal (Strep A) bacteria globally. Strep A is highly transmissible and spreads from person to person mostly via the respiratory route from sore throats. Strep A is typically known for causing sore throats and skin infections in younger children.  In rare cases, it can lead to more severe conditions like sepsis and toxic shock if the bacteria invade the bloodstream or tissue. While adults are often immune to Strep A sore throats and skin infections, both adults and children are very susceptible to the invasive form of the infection. A particularly alarming consequence of repeated Strep A infections is the autoimmune-induced damage to heart valves, termed rheumatic heart disease (RHD). RHD affects approximately 50 million people worldwide, predominantly in middle- and low-income countries. Currently, there is no vaccine available for Strep A. The development of immunity to Strep A over time, including the identification of specific bacterial antigens crucial for targeting by the immune system or future vaccines, remains poorly understood. Additionally, the distinction between detrimental immune overreactions to Strep A, leading to RHD, and the desirable protective immunity is not clearly defined.

In response to this global health challenge, an international collaboration of scientists has established a comprehensive network to investigate the bacterial causes of sepsis and heart damage caused by Strep A. The iSpy Network (immunity to Streptococcus pyogenes), led by Imperial College London (London, UK), along with the University of California San Diego (La Jolla, CA, USA), unites 28 researchers from 11 countries. This diverse group of experts in immunology, infectious disease, epidemiology, vaccinology, and experimental medicine will engage in a five-year project. Their goal is to utilize a broad spectrum of advanced techniques to delve into Strep A immunity with unprecedented detail, ultimately contributing significantly to reducing the global impact of Strep A.

The iSpy-LIFE sub-network aims to uncover how effective immunity to Strep A develops in children, following natural infection over time. This research, involving young children, school-age pupils, and adults, may provide insights into genuine immunity against Strep A and guide the development of a vaccine that mimics and accelerates this immunity in children. Additionally, the iSpy-EXPLORE sub-network is set to explore the nature of protective immune responses in experimental models exposed to promising Strep A vaccine candidates. It will also assess human immune responses in healthy volunteers experimentally exposed to Strep A infections. Collectively, these efforts are poised to enhance understanding of both beneficial and detrimental immunity to Strep A, paving the way for a future vaccine that could protect against strep throat, invasive infections, and RHD.

“The RHD patients we see in LMICs generally present with advanced disease and complications such as heart failure,” said Professor Liesl Zuhlke, a pediatric cardiologist at The University of Cape Town and iSpy team member. “Many require cardiac surgery or percutaneous intervention which are often not available, resulting in significant mortality and morbidity and incurring huge out-of-pocket costs to families and communities. We desperately need data on transitions between the various forms of Strep A diseases and how we can intervene to prevent these manifestations.”

Related Links:
Imperial College London
University of California San Diego 

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