The C-terminal region of the M-protein of Streptococcus pyogenes is a major target for vaccine development. The major feature is the C-repeat region, consisting of 35-42 amino acid repeat units that display high but not perfect identity. SV1 is a S. pyogenes vaccine candidate that incorporates five 14mer amino acid sequences (called J14_i variants) from differing C-repeat units in a single recombinant construct. Here we show that the J14_i variants chosen for inclusion in SV1 are the most common variants in a dataset of 176 unique M-proteins. Murine antibodies raised against SV1 were shown to bind to each of the J14_i variants present in SV1. Additionally this sera reacted with five J14_i variants not present in SV1. Antibodies raised to the individual J14_i variants were also shown to bind to multiple but different combinations of J14_i variants, supporting the underlying rationale for the design of SV1. Next, the immuno-safety of SV1 was assessed using a rat model of valvulitis. In this model, rat myocardial tissue displayed changes consistent with valvulitis following immunisation with control M5 protein, but not SV1. Together these results suggest that SV1 is promising vaccine candidate that will elicit antibodies that recognise the majority of M-types, and thereby may offer protection against most circulating strains.