Poster Presentation BACPATH 2019

Enhancing group A streptococcal vaccine design through global population genomics and non-human primate infection studies. (#115)

Mark R Davies 1 , Tania Rivera-Hernandez 2 , Liam McIntyre 1 , Diane G Carnathan 3 , Jake A Lacey 4 , John A Lees 5 , Rebecca J Towers 6 , Sebastian Duchene 1 , Amanda J Cork 2 , Phil M Giffard 6 , Bart J Currie 6 , Allan Saul 7 , Steven Y.C. Tong 4 6 8 , Guido Silvestri 3 , Gordon Dougan 9 , Mark J Walker 2
  1. Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institite for Infection and Immunity, Melbourne, Vic, Australia
  2. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
  3. Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA
  4. Doherty Department, Doherty Institute, The University of Melbourne, Melbourne, Vic, Australia
  5. Department of Microbiology, New York University School of Medicine, New York, USA
  6. Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia
  7. GSK Vaccines Institute for Global Health, Sienna, Italy
  8. Victorian Infectious Diseases Service, The Royal Melbourne Hospital and the University of Melbourne, at the Doherty Institute , Melbourne, Vic, Australia
  9. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK

The development of a group A streptococcal (GAS) vaccine has been hindered by a number of hurdles including the high serotypic diversity of the pathogen, autoimmune complications following repeated GAS infections, and the lack of non-murine models to validate proposed GAS vaccine formulations. To overcome these hurdles, we generated a global GAS genome database to unravel the evolutionary dynamics of this major human pathogen. This database of 2,083 genomes were obtained from 22 countries, with a focus on sampling from streptococcal endemic settings. We identified a core panel of pre-clinical GAS vaccine antigens that would provide theoretical global coverage on the basis of >99% antigen carriage and <2% sequence heterogeneity. Using this platform, 5 conserved antigens (arginine deiminase [ADI], C5a peptidase [SCPA], streptolysin O [SLO], interleukin-8 [IL-8] protease [SpyCEP], and trigger factor [TF]), that have not been linked to autoimmune complications yet are highly conserved within a global context, were investigated as a putative multi-component vaccine formulation. We developed a non-human primate (NHP) infection model of GAS pharyngitis and evaluated the protective efficacy of the 5 conserved antigen formulation termed ‘Combo5’. Antibody responses against all Combo5 antigens were detected in NHP serum, and immunised NHPs showed a reduced pharyngitis and tonsillitis compared to controls. Within an evolving global bacterial pathogen such as GAS, we have identified a number of proposed pre-clinical GAS vaccine antigens that fulfil the criteria for a global vaccine and provide protection from pharyngitis in a NHP model. Our work establishes a technical and experimental framework for the development of a global GAS vaccine.