Group A Streptococcus (GAS), a gram-positive pathogenic bacterium has been accountable for variety of invasive and non-invasive diseases which may later lead to life threating diseases like rheumatic fever and rheumatic heart diseases. Although research has been ongoing since 1923, vaccines against GAS are not yet available that requires cell-mediated and mucosal immunity stimulation. Thus investigation into new classes of vaccines has become one of the forefronts of medical research. 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 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, herein, 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 which was either physically mixed or chemically conjugated to hydrophobic polymers (polymethylacrylate or poly(N-isopropylacrylamide nanoparticles)). All vaccine candidates formed nanoparticles and were capable of inducing the production of opsonic epitope-specific antibodies, following the subcutaneous immunization in mice. Among three different shapes of nanoparticles; sphere, rod and worms, it was found that the rod shaped nanoparticles specifically elicited a highest level of IgG titres than CFA based adjuvant after the first boost. Thus, we have successfully demonstrated that the shape plays vital role in inducing strong humoral immune responses.