Serological responses to Streptococcus pyogenes vaccine candidate antigens suggests that Streptococcus dysgalactiae is the predominant cause of lower limb cellulitis

Abstract

Abstract Background A future Streptococcus pyogenes (Strep A) vaccine will ideally prevent a significant burden of lower limb cellulitis, however, natural immune responses to proposed vaccine antigens following an episode of cellulitis remain uncharacterised. Methods We enrolled 63 patients with cellulitis and 26 with invasive beta haemolytic streptococci (BHS) infection, utilising a multiplexed assay to measure IgG against Strep A vaccine candidate antigens, including: streptolysin O (SLO), deoxyribonuclease B (DNB), group A carbohydrate (GAC), C5a peptidase (ScpA), cell envelope proteinase (SpyCEP), and adhesion and division protein (SpyAD). Responses in the invasive cohort were used to predict the infecting aetiology in the cellulitis cohort. Results Of 41 patients with non-bacteraemic cellulitis and paired serological samples, 68.3% had evidence of BHS infection by conventional anti-SLO and/or anti-DNB criteria. A positive serological response to at least one of the tested antigens was seen in 78.0% of the cellulitis cohort. Individually, anti-SLO (58.5%), anti-SpyAD (46.3%), and anti-ScpA (39.0%) were the most common. Based on principal component analysis, increases in these three antibodies, without responses to DNB, GAC and SpyCEP characterised Streptococcus dysgalactiae subspecies equisimilis (SDSE) infection. Conclusions SDSE appears to be the predominant cause of lower limb cellulitis. Effective Strep A vaccines incorporating antigens which provide additional cross protection against SDSE may prevent a significant burden of lower limb cellulitis.