Poster Presentation Lorne Infection and Immunity 2022

Increased breadth of Group A Streptococcus antibody responses in children with acute rheumatic fever compared to precursor pharyngitis and skin infections (#226)

Alana L Whitcombe 1 , Reuben McGregor 1 , Julie Bennett 2 , Michael Baker 2 , Nicole J Moreland 1
  1. School of Medical Sciences and Maurice Wilkins Centre, University of Auckland, Auckland, New Zealand
  2. Department of Public Health, University of Otago, Wellington, New Zealand

Group A Streptococcus (GAS) causes superficial pharyngitis and skin infections as well as serious autoimmune sequelae such as acute rheumatic fever (ARF). ARF can progress to chronic rheumatic heart disease that is associated with significant morbidity and mortality in Māori and Pacific children in New Zealand and Aboriginal children in Australia. Candidate vaccines that can prevent GAS infections are being developed but have not yet reached licensure, and the limited understanding of ARF pathogenesis presents a major hurdle for the field. Immune priming by repeated GAS infections is thought to trigger ARF, and there is growing evidence for the role of skin infections in this process. The aim of this study was to utilise our recently developed 8-plex immunoassay to characterise antibody responses in sera from New Zealand children with a range of clinical GAS disease; ARF (n=80), GAS-positive pharyngitis (n=117), GAS-positive skin infection (n=51) and closely matched healthy controls (n=134). The 8-plex assay comprises antigens used in clinical serology for the diagnosis of ARF (SLO, DNase B and SpnA), and five conserved putative GAS vaccine antigens (Spy0843, SCPA, SpyCEP, SpyAD and the Group A carbohydrate). Serological responses differed by ethnicity, with Māori and Pacific children having significantly higher GAS antibodies than other ethnic groups at baseline and following infection. Antibody levels slowly waned over time, though the rate of decay appeared to be quicker for SpnA and Spy0843 highlighting differences in kinetics between antigens. Most notably, the magnitude and breadth of antibodies in ARF was very high, giving rise to a distinct serological profile. An average of 6.5 antigen‑specific reactivities per individual was observed in ARF, compared to 3.9 in skin infections and 3.1 in pharyngitis. This suggests the ARF profile is the result of repeated precursor pharyngitis and skin infections that progressively boost antibody breadth and magnitude.