Poster Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

System Serology Reveals Correlates of Functional Group A Streptococcus Antibody Responses In Children With Pharyngitis (#294)

Reuben McGregor 1 2 , Natalie Lorenz 1 2 , Alana L Whitcombe 1 , Aimee Paterson 1 , Julie Bennett 1 2 3 , Michael Baker 2 3 , William Kelton 2 4 5 , Amy Chung 6 , Nicole J Moreland 1 2
  1. Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
  2. Maurice Wilkins Centre for Biodiscovery, Auckland, New Zealand
  3. Department of Public Health, University of Otago, Wellington, New Zealand
  4. University of Waikato, Te Huataki Waiora School of Health, Hamilton, New Zealand
  5. University of Waikato, Te Aka Mātuatua School of Science, Hamilton, New Zealand
  6. Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia

Group A Streptococcus (Strep A) is a globally important pathogen for which no licenced vaccine currently exists. Defining the immunological basis of protection is critical to identifying a correlate of protection, a key element for future vaccine development. Understanding Strep A immunity is challenging due to the complex interplay between diverse virulence factors and immune system components. Here, we use a high-dimensional Strep A-specific systems serology array to identify correlates of a functional immune response in pharyngitis. The array quantifies 121 antibody features, including isotypes, Fc receptor and complement binding, and was engineered to detect both conserved and type specific (M6/T6) responses. This approach was combined with opsonophagocytic killing assays (OPKA) and applied to children with pharyngitis caused by emm6 and non-emm6 strains, as well as healthy controls. Systems serology tools were used to identify serological features linked to pharyngitis and type-specific killing. Total IgG responses to conserved antigens were higher in both pharyngitis groups, while IgG3 responses were most prominent for type specific antigens (M6/T6) and in children with emm6 pharyngitis. Multivariate analysis linked M-type-specific antibody responses and engagement of the activating Fc receptor (FcγRIIa) with functional killing. This feature was able to predict killing with 100% accuracy in a distinct set of sera, confirming identification of a correlate of a functional antibody responses for emm6 strains in children. Broader application of this systems serology approach could aid in deconvoluting the Strep A immune response, with potential to identify correlates of protection in future vaccine trials.