Expanding strain coverage of a Group A Streptococcus pilus-expressing Lactococcus lactis mucosal vaccine.

Abstract

Group A Streptococcus (GAS) is a human pathogenic bacterium that can trigger a wide range of diseases, including the autoimmune diseases acute rheumatic fever and rheumatic heart disease, causing major morbidity and mortality in many low- and middle-income countries. Primary intervention programs have had limited success thus far, and a licenced vaccine has yet to be developed. The pilus of GAS is known to be involved in host cell adhesion, biofilm formation and immune evasion. We have a mucosal vaccine in development that expresses the pilus of GAS on the surface of the non-pathogenic bacterium Lactococcus lactis. To expand strain coverage, we combined seven L. lactis constructs, each expressing a different GAS pilus variant and investigated the systemic and mucosal immune responses following immunisation. Mice immunised with this combination showed specific IgG and IgA responses to the GAS pilus proteins of vaccine strains, at levels comparable to mice immunised with a single construct. Cross-reactivity to pilus proteins of non-vaccine strains was also evident. Furthermore, protective efficacy against a homologous strain of GAS in a murine nasopharyngeal colonisation model was observed. Overall, this study provides further evidence for using pilus-expressing lactic acid bacteria as a vaccine to prevent upper respiratory tract GAS infections.