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

Enhanced protection from skin, mucosal and invasive Group A Streptococcal disease following vaccination with native and mutated cryptic epitopes (#117)

Michael Good 1 , Manisha Pandey 1 , Mehfuz Zaman 1 , Therese Nordstrom 2 , Victoria Ozberk 1 , Yun Shi 1 , Ainslie Calcutt 1 , Emma L Langshaw 1 , Jessica Powell 1 , Mei Fong Ho 1 , Zachary N Phillips 1 , Thomas Haselhorst 1 , Mark von Itzstein 1 , Istvan Toth 3 , Michael R Batzloff 1
  1. Griffith University, Southport, QLD, Australia
  2. QIMR Berghofer Medical Research Institute, Brisbane
  3. The University of Queensland, School of Chemistry and Molecular Biosciences, Australia

The development of vaccines for GAS will require technologies that enable induction of immune responses to multiple polymorphic epitopes or to a conserved epitope/s that are targets of protective antibodies. Synthetic peptides enable the use of minimal epitopes significantly reducing the chance of autoimmune pathology; however, peptides suffer from poor immunogenicity. Antibodies to a conserved minimal epitope, J8, from the M protein can kill multiple strains of GAS and protect from skin and mucosal infection even though J8 is cryptic and immunologically inert following infection. We defined an additional conserved sub-dominant epitope from Spy-CEP, which, when combined with J8 provides enhanced protection, particularly against CovR/S mutants. We can deliver these immunogens via either injection or intranasal delivery and show that they protect against skin and URT infections and invasive GAS disease but require three immunizations to do so.

To enhance the immunogenicity of J8, we have undertaken a series of rational mutations leading to a novel peptide which is highly immunogenic, inducing protection after only a single immunization. Surprisingly, sera from vaccinated mice recognize the non-mutated parent peptide and bind the surface of GAS significantly better than sera from mice vaccinated with the parent peptide. Molecular dynamic simulation suggested that the mutations resulted in enhanced helical folding of the vaccine peptide, which may explain the its efficacy as a vaccine.

The results demonstrate a generic strategy that can enhance the utility of peptides as vaccines and strongly support the development of a GAS vaccine based on minimal epitope synthetic peptides.