Group A Streptococcus (GAS) is a host-adapted bacterial pathogen that causes a significant healthcare burden worldwide. GAS is the most common cause of bacterial pharyngitis and a significant driver of antibiotic prescription for children, contributing to antibiotic resistance selection pressures for bacterial pathogens. While GAS causes superficial disease, it is also responsible for severe invasive infections and autoimmune sequalae such as rheumatic heart disease.
Despite the need for a safe and efficacious GAS vaccine for human use, a licensed vaccine is not available. Vaccine development has been hindered due to high serotype diversity, no defined correlates of protection and potential for the development of autoimmune syndromes associated with GAS M protein and group A carbohydrate antigens.
A recently developed messenger RNA (mRNA)-lipid nanoparticle (LNP) formulation of the preclinical GAS vaccine candidate Combo#5 is comprised of five mRNA transcripts that encode for five highly conserved GAS antigens, with low naturally occurring sequence variation providing high theoretical vaccine coverage. Combo#5 mRNA-LNP significantly enhanced survival of humanised plasminogen (hPlg) and BALB/c mice against invasive M1 serotype GAS infection on a 3-dose vaccination schedule. A preclinical model demonstrated high antibody titres in sera of mice vaccinated on a 2-dose schedule suggesting the retention of protective efficacy while reducing total vaccination doses. The high theoretical coverage of vaccine antigens suggests heterologous protective efficacy of Combo#5 mRNA-LNP independent of GAS emm serotype. This study assesses the protective ability of Combo#5 mRNA-LNP on a reduced vaccination schedule and across multiple emm serotypes in a mouse model.