Background: Group A Streptococcus (GAS) is a gram-positive pathogenic bacterium that cause variety of invasive and non-invasive diseases ultimately leading to life threating diseases like rheumatic fever and rheumatic heart diseases. Since traditional vaccines that use the whole GAS pathogen may trigger an autoimmune response, B-cell fragments from M-protein like J8 peptide epitope (QAEDKVKQSREAKKQVEKALKQLEDKVQ) and universal T-helper epitope PADRE (AKFVAAWTLKAAA) were synthesized to develop different peptide constructs. One of the major challenges to overcome in the development of such peptide vaccines is the need for a strong immunostimulant (adjuvant) or delivery system to boost the vaccines’ immunogenicity as peptides are poor immunogens on their own. Considering the associated toxicity of currently available adjuvants that are not only non-biodegradable but invariably invoke adverse reactions, allergic responses, and inflammation.
Methodologies: Our study focuses on a development of a potent polymer-based delivery system that is able to induce immune responses against the peptide epitope, without the use of any additional adjuvant. The antigen PADRE-J8 was synthesized using solid phase peptide synthesis and it was either physically mixed or chemically conjugated to rod and worm shaped polymeric nanoparticles. Different shapes of vaccine formulation using the polymer were immunized subcutaneously in the mice and assessed for the opsonic activity against GAS strain.
Findings: All vaccine candidates induced the production of opsonic epitope-specific antibodies, following the subcutaneous immunization in mice. Interestingly, after first boost, rod shaped vaccine candidates specifically elicited stronger systemic immune responses than a commercial adjuvant, CFA (Complete Freund's Adjuvant).
Conclusions: We demonstrated, for the first time, the ability of different shapes of polymeric delivery system to act as a vehicle for the delivery of GAS peptide antigens to treat GAS infections.