Neglected Diseases
Rheumatic fever is a bacterial infection caused by Streptococcus pyogenes (also known as Group A streptococcus, GAS) that most commonly affects children aged 5-14 years.
It usually follows untreated bacterial throat infections, and without treatment can lead to complications such as rheumatic heart disease, in which the heart valves are permanently damaged. It may also progress to heart failure and stroke.
Prophylactic use of antibiotics is the only preventive measure currently available for preventing rheumatic fever and its associated complications, such as rheumatic heart disease. Such widespread use of antibiotics is potentially vulnerable to and causative of antimicrobial resistance, meaning that a vaccine to prevent rheumatic fever is a much-needed medical countermeasure. Currently, the vaccine development pipeline is mostly at the stage of pre-clinical testing, and only a handful of candidates have undergone human safety trials. These include StreptAnova, the most advanced candidate, which successfully completed a Phase I trial in 2020.
Two group A Streptococcus (GAS) vaccines are currently in active clinical development – J8-K4S2 and p*17-K4S2. Both are peptide vaccines constructed on highly conserved C-terminal of M protein and modified B-cell epitope from SpyCEP. The Phase I trial investigating these vaccines is expected to be completed by the end of 2023. Another M protein-based, 30-valent vaccine, StreptAnova, was found to be safe and immunogenic. Several non-M protein-based vaccines, including some utilising the Group A Carbohydrate (GAC) approach, are in preclinical development. GAC-based vaccines have the potential to provide protection against more than 99% of serotypes present globally.