Background
Each year, S. pyogenes causes over half a million deaths due to invasive infections and autoimmune sequelae, yet no licensed vaccine is available. Affinity-purified pooled human intravenous immunoglobulin (IVIG) contains antibodies that confer protection against streptococcal infection in mice and human whole blood. Using a highly protective anti-S. pyogenes IVIG preparation made from extracts from twenty S. pyogenes strains, representing four leading UK serotypes, we identified 20 conserved antigenic targets.
Aims and methods
To screen the panel of 20 potential vaccine antigens for protective efficacy (either alone or in combinations), we prepared saRNA constructs for each antigen. We then transfected HEK293 cells with each saRNA to confirm expression. The saRNAs were then formulated in LNPs to vaccinate C57/BL6 mice.
Results
18 out of 20 (90%) saRNA constructs were successfully expressed in HEK293 cells, either within cell lysates or secreted. In a pilot study, a two-dose regimen was employed for saRNA with a 28-day interval. Vaccination with saRNA encoding ScpA, SpyCEP, SpyAD, and Pullulanase resulted in high titre antibodies against each protein. Titres against cognate antigens were significantly higher in saRNA-vaccinated mice compared to positive controls vaccinated in a three-dose M protein/Alum regimen.
Summary
New tools are needed to speed up vaccine discovery and identify optimal antigen combinations. Vaccines against highly pathogenic bacteria like S. pyogenes must include multiple antigens to prevent vaccine escape and provide synergistic modes of protection. The saRNA platform is valuable for rapidly and efficiently screening novel bacterial vaccine antigens, both individually and in combinations.