Research opportunities for the primordial prevention of rheumatic fever and rheumatic heart disease—streptococcal vaccine development: a national heart, lung and blood institute workshop report

Abstract

Streptococcus pyogenes,also known as group A streptococcus (StrepA), is a bacterium that causes a range of human diseases, including pharyngitis, impetigo, invasive infections, and post-infection immune sequelae such as rheumatic fever and rheumatic heart disease. StrepA infections cause some of the highest burden of disease and death in mostly young populations in low-resource settings. Despite decades of effort, there is still no licensed StrepA vaccine, which if developed, could be a cost-effective way to reduce the incidence of disease. Several challenges, including technical and regulatory hurdles, safety concerns and a lack of investment have hindered StrepA vaccine development. Barriers to developing a StrepA vaccine must be overcome in the future by prioritising key areas of research including greater understanding of StrepA immunobiology and autoimmunity risk, better animal models that mimic human disease, expanding the StrepA vaccine pipeline and supporting vaccine clinical trials. The development of a StrepA vaccine is a complex and challenging process that requires significant resources and investment. Given the global burden of StrepA infections and the potential for a vaccine to save lives and livelihoods, StrepA vaccine development is an area of research that deserves considerable support. This report summarises the findings of the Primordial Prevention Working Group-VAX, which was convened in November 2021 by the National Heart, Lung, and Blood Institute. The focus of this report is to identify research gaps within the current StrepA vaccine landscape and find opportunities and develop priorities to promote the rapid and successful advancement of StrepA vaccines.

Prospects for the future: supporting the elimination of rheumatic heart disease – a National Heart, Lung, and Blood Institute Workshop Proceedings

“…Interdisciplinary partnerships were identified as integral in order to support the development of vaccines that are broadly efficacious, tolerable, safe and, most importantly, accessible to those most at risk. 17 The primary prevention WG discussions focused on the diagnosis and treatment of GAS infections preceding ARF sequelae in collaboration with community and governmental partners, to enable the codesign of feasible strategies that improve access to available evidence-based interventions. 15 The secondary prevention WG addressed questions related to the diagnosis and management of people with established RHD to prevent disease progression including long-term penicillin prophylaxis.…”

“…During the workshop, each WG presented their findings that are described in further detail within this supplement. [13][14][15][16][17] Multiple breakout sessions were held to develop action plans, allowing all the WGs and participants to reflect on the outputs of the workshop, as well as describe the opportunities that ought to be addressed using fundamental discovery science, clinical research and implementation science to support the elimination of RHD. Unique features from each breakout session are included in table 1.…”