Group A Streptococcus (GAS), a gram-positive bacterium, causes a broad spectrum of infections with high morbidity worldwide. Antibiotics only can treat the early stage of GAS infections instead of fatal GAS complications. Currently, no commercial vaccines are approved to treat GAS infection. Immunization with live-attenuated and inactivated whole pathogens can induce the potent adaptive immune response protection against infections; however, they are not fully safe, causing adverse side effects (e.g., inflammations, autoimmune and allergic response). Peptide-based subunit vaccines using antigenic peptides selected from pathogenic proteins to induce the adaptive immune response. Peptide-based subunit vaccines are pure, simple production and achieve batch to batch consistency, eliminating undesirable immune responses. However, the poor immunogenicity of peptide-based subunit vaccines requires potent adjuvants and delivery system to improve the adaptive immune response.
In our research, we applied negatively charged polyglutamic amino acids (E10) conjugated with the antigenic peptides (B-cell epitope J8 derived from GAS M protein and T-helper epitope, P25), then physically mixing with lipoamino acids (10 glutamate acids), forming vaccine complexes with self-adjuvanting delivery system. Vaccine candidates were designed to determine whether charge of vaccine candidates can affect the immune response and whether a simple physical mixture of self-adjuvanting vaccines is sufficient to induce the stronger humoral immune response compared to conjugation.
All vaccine candidates were synthesized by Fmoc-solid-phase peptide synthesis (SPPS) and tested their secondary structure and characterizes. All vaccine conjugates formulated particles and elicited significant IgG titres following subcutaneous immunization, while physical mixture is unable to enhance the stronger humoral immune response compared to conjugation.