Poster Presentation BacPath 13: Molecular Analysis of Bacterial Pathogens Conference 2015

Understanding the disease pathogenesis of group A streptococcus upper respiratory tract infection to help improve vaccine and vaccination strategies with J8-DT (#168)

Victoria Ozberk 1 , Mehfuz Zaman 1 , Emma Langshaw 1 , Ainslie Calcutt 1 , Jessica Powell 1 , Michael R. Batzloff 1 , Manisha Pandey 1 , Michael F. Good 1
  1. Griffith University, Gold Coast, QLD, Australia

Group A streptococcus (GAS, Streptococcus pyogenes) colonises the throat, accounting for over 616 million cases of pharyngitis annually. Up to 3% of these cases can lead to rheumatic fever and rheumatic heart disease, thus emphasising the need for an effective mucosal GAS vaccine. Understanding the host pathogen interactions of GAS during upper respiratory tract (URT) colonisation would enhance the development of mucosal vaccine strategies.

Preliminary work assessed the efficacy of intramuscular (IM) immunisation with J8-DT/Alum in protection against intranasal (IN) GAS challenge.  J8 is a conserved epitope from the M-protein of GAS and has been conjugated to diphtheria toxoid (DT) and formulated with Alum.  IM immunization with J8-DT resulted in high levels of J8-specific serum IgG and undetectable mucosal IgA. Following IN challenge, the bio-burden at mucosal surfaces and organs demonstrated that IM vaccination did not significantly effect bacterial burden in the mucosa. 

Preliminary data emphasized the need for a delivery system to elicit mucosal IgA.  Liposomal vaccine delivery systems have the ability to induce immune responses.  Further investigations assessed the efficacy of IN immunisation with J8-Liposomes in protection against IN GAS challenge.  Following immunisation with J8-Liposomes, serum IgG and mucosal IgA levels were detected. Protection was evident in throat swabs and nasal shedding with undetectable bio-burden in immunised mice on day 2 post-challenge.

The J8 peptide alone has been found to be significantly less effective against hyper-virulent CovR/S mutant GAS. This is correlated with up-regulation of SpyCEP in CovR/S mutant GAS. Liposomal vaccine strategies will include S2, a minimal epitope within SpyCEP that is the primary target for anti-SpyCEP antibodies that could protect IL-8 from SpyCEP-mediated proteolysis.  For the development of an optimal GAS vaccine, further studies will involve IN immunisation with J8+S2-Liposomes that are capable of stimulating mucosal IgA and protecting against mutant and wild-type GAS.