Oral Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

Phase I Trial of a Peptide-based Vaccine to Prevent Group A Streptococcal Infection (118111)

Michael F. Good 1 , Manisha Pandey 1 , Simone Reynolds 1 , Victoria Ozberk 1 , Vanessa Vanessa Meier-Stephenson 2 , Michael Hawkes 2 , Ailin Lepletier 1 , Ainslie Calcutt 1 , Christie Short 1 , Ijeoma Ogbuehi 2 , Alena Tse-Chang 2 , Catherine Burton 2 , Kelly Kim 2 , Conar O'Neil 2 , William Stokes 2 , Maryna Yaskina 2 , Ben Tyrrell 2 , Scott Jamieson 3 , Eloise Keeffe 1 , Chris Davis 1 , Joshua Osowicki 4 , Andrew Steer 4 , Greg Tyrrell 2 , D. Lorne Tyrrell 2 , Michael Houghton 2
  1. Institute for Biomedicine and Glycomics, Griffith University, Southport, QLD, Australia
  2. University of Alberta, Edmonton, Alberta, Canada
  3. Northern Alberta Clinical Trials and Research Center, Edmonton, Alberta, Canada
  4. Murdoch Children’s Research Institute, Melbourne, Victoria, Australia

We identified minimal conserved epitopes on the M-protein (J8, P*17) and the anti-neutrophil chemoattractant virulence factor, SpyCEP (K4S2), of Streptococcus pyogenes (‘Strep A’) as targets of protective antibodies.  Vaccines combining either M-protein epitope and K4S2 induce murine antibodies that bind M-protein, neutralize SpyCEP and protect the upper respiratory tract and skin against all Strep A strains that we studied.  Although the vaccine epitopes are cryptic and not recognized in naive mice following infection, infection of vaccinated mice leads to antibody boosting and enhanced protection, suggesting that vaccine-induced immunity will be long-lasting and significantly improve over time.

Thirty healthy adult volunteers were recruited by The North Alberta Clinical Trials and Research Centre. Three doses of each of two GMP-grade vaccines (J8-CRM197/K4S2-CRM197/Alum; P*17-CRM197/K4S2-CRM197/Alum) or placebo (rabies vaccine, RabAvert) were administered to volunteers at 0, 3 and 6 weeks. The first 10 volunteers (5 for each vaccine candidate) to receive the vaccines have been assessed.  There were no attributable high grade adverse events.  The remaining volunteers will be assessed following unblinding of those cohorts.  

Both vaccines demonstrated strong immunogenicity in all participants. A competitive binding assay was established and demonstrated binding of vaccine-induced antibodies from all vaccinated participants out to 6 months to the surface of multiple Strep A strains.  Antibody avidity increased with sequential vaccinations. Vaccine-induced antibodies could kill Strep A in an in vitro opsonophagocytic assay and protected IL-8 from SpyCEP-mediated proteolysis.  We plan to advance this vaccine into a Phase Ib challenge trial, followed by a Phase II paediatric trial.