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

Liposomal peptide vaccine delivery system induces protective humoral and cellular immune responses against group A streptococcus in the upper respiratory tract (#171)

Mehfuz Zaman 1 , Victoria Ozberk 1 , Emma L Langshaw 1 , Sharareh Eskandari 1 , Manisha Pandey 1 , Ainslie Calcutt 1 , Jessica Powell 1 , Mei-Fong Ho 1 , Zachary N Philips 1 , Michael R Batzloff 1 , Michael F Good 1
  1. Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia

The most common disease following GAS colonization of the upper respiratory tract (URT) is pharyngitis. Rheumatic heart disease (RHD) can follow untreated pharyngeal infections. Globally, there is estimated to be 62–78 million individuals with RHD that results in over 300,000 deaths per year.

Established correlates of protection show that IgA-specific mucosal immunity prevents pharyngeal colonization. To develop a vaccine that induces an IgA response, we constructed a liposomal vaccine consisting of a GAS-specific conserved B-cell epitope from the surface M protein (‘J8’) and a source of T-helper cell stimulation provided by diphtheria toxoid and delivered this intranasally (‘J8-Lipo-DT’). 

Post immunization, we observed a significant IgA mucosal antibody response.  Post-challenge with GAS the bacterial load in the nasal discharge was significantly lower. Mice also showed significant protection against infection oF the pharyngeal surface and nasal associated lymphoid tissue. We measured the cytokine responses of spleen cells from immunized mice following in vitro stimulation. Antigen-specific IFN-γ and IL-6 from spleen cells from immunized mice was observed. IL-6 is a signal for neutrophil production and neutrophils are essential for IgA-mediated opsonization of GAS. We thus immunized IL6− /− and control mice with J8-Lipo-DT and observed that the IL6− /− mice had significantly higher total streptococcal tissue bioburden post-challenge in comparison to wildtype mice.

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