Oral Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Protocol for a group A streptococcal pharyngitis human challenge study (#109)

Joshua Osowicki 1 2 , Kristy I Azzopardi 1 , Ciara Baker 1 , James B Dale 3 , Michael F Good 4 , Manisha Pandey 4 , Claire S Waddington 5 , Pierre R Smeesters 1 2 6 , Jonathan R Carapetis 5 , Michael R Batzloff 4 , Andrew C Steer 1 2
  1. Group A Streptococcal Research Group, Murdoch Children's Research Institute, Melbourne, VICTORIA, Australia
  2. Centre for International Child Health, University of Melbourne, Melbourne, Victoria, Australia
  3. Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, United States
  4. Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia
  5. Telethon Institute for Child Health Research, University of Western Australia,, Perth, Western Australia, Australia
  6. Department of Pediatrics, Academic Children Hospital Queen Fabiola, Université Libre de Bruxelles, Brussels, Belgium

The road to a human GAS vaccine to prevent morbidity and mortality across the spectrum of GAS diseases has been tortuous and beset by critical knowledge gaps. Human challenge studies informed the development of the first human vaccines and there has been resurgent interest in modern human challenge models to advance the development pathway for new vaccines, incorporating stringent ethical and safety standards, and advanced immunology and microbiology techniques. A successful GAS human challenge model will help negotiate impediments on the vaccine development pathway by advancing understanding of human immune responses to GAS and delivering preliminary efficacy data for candidate vaccines to provide confidence to industry and regulators considering phase III studies. Non-vaccine interventions such as new secondary prophylaxis strategies (e.g. long-acting penicillin) and molecular diagnostics could also be examined in a GAS human challenge model.

To build a human challenge model, our primary objective is to establish the GAS inoculum (dose) required to safely achieve a reliable pharyngitis attack rate of ³60% in healthy adults following direct oropharyngeal inoculation of GAS in an observational dose-escalation inpatient study followed by periodic outpatient visits over six months. A secondary objective is to describe the immunobiology of GAS pharyngitis in healthy adults byevaluating systemic and mucosal immune responses, including to potential vaccine antigens. This presentation will highlight major aspects of the study protocol and the potential for a successful model to advance vaccine development and other research to reduce the burden of GAS diseases.