Oral Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2023

A Synthetic Peptide Vaccine Based on the Conserved Region of the Streptococcal M-Protein and the IL-8 Protease, SpyCEP, Demonstrates Prophylactic and Therapeutic Efficacy Against Streptococcal Superficial and Invasive Infections (#29)

Manisha Pandey 1 , Victoria Ozberk 1 , Ailin Lepletier 1 , Simone Reynolds 1 , Jessica Dooley 1 , Ainslie Calcutt 1 , Jamie-Lee Mills 1 , James McCluskey 2 , Jenny Robson 3 , Gregory Tyrell 4 , Natkunam Ketheesan 5 , Michael Good 1
  1. Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia
  2. Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  3. Sullivan and Nicolaides Pathology, Brisbane, Australia
  4. University of Alberta, Edmonton, Canada
  5. University of New England, Armidale, NSW, Australia

Infections with Streptococcus pyogenes (StrepA) and their sequelae are responsible for an estimated 18 million cases of serious disease, with 700 million new primary cases and 500,000 deaths per year. The majority of the deaths are due to rheumatic heart disease (RHD) or invasive StrepA disease (ISD).  RHD has an autoimmune aetiology, and the majority of cases occur in developing nations or amongst the Indigenous populations in developed countries.  ISD has high mortality rates in even the best-equipped facilities.  Despite the burden of disease, there is currently no vaccine available. Vaccine development has been hampered by antigenic diversity of the M-protein and by the risk that vaccination may lead to autoimmune pathology. To overcome these impediments, we defined conserved minimal cryptic-epitopes to create safe vaccines which could induce pan-strain opsonising antibodies.

The two conserved cryptic B-cell epitopes (J8, p*17) from the M-protein, and ‘S2’ (from Spy-CEP) were conjugated to Cross Reactive Material (CRM) and conjugate combinations formulated in Alhydrogel. The combination vaccines were tested in murine models of the upper respiratory tract, skin, or invasive infection. Vaccination led to enduring and protective immunity, which was evident for over 12-months post vaccination, even though the antibody levels had declined significantly at that time. The safety of vaccines was also confirmed in a formal toxicology study as well as in a rat autoimmune valvulitis model. Furthermore, to assess the immunotherapeutic potential of vaccine-induced antibodies, the vaccine sera or the monoclonal antibodies against vaccine antigens were tested in a murine model of streptococcal toxic shock syndrome (STSS).  Immunotherapy with vaccine antibodies quickly resolved established disease by acting to clear the infection and ablate the mitogenic and inflammatory activity of the M protein. This has important implications for the development of clinical therapeutics. The vaccines are currently in a Phase 1 clinical trial.