Vaccination is the cost-effective approach to prevent infectious diseases. Weakened or dead whole organism-based vaccines may be associated with the risks of allergic responses. Peptide-based vaccines possess greater safety profile compared to whole organism vaccines due to exclusion of unwanted biological material and ease of synthesizing it in highly pure state and large scale. However, peptide-based vaccines are poorly immunogenic alone and demand an addition of immunoadjuvants. In our lab, we developed a novel self-adjuvanting delivery system to improve the immunogenicity of group A streptococcus (GAS) peptide-based vaccines. We conjugated anionic polymer polyglutamic acid to a peptide comprising of GAS J8 B cell epitope and universal T-helper epitope. The peptide-polyglutamic acid conjugates were further formulated into nanoparticles by complexation with cationic trimethyl chitosan (TMC). The mice vaccinated with this nanovaccine generated higher serum antibody titers compared to mice receiving peptide admixed with cholera toxin B mucosal adjuvant (positive control). We further optimized this nanovaccine by incorporating lipid moiety and established structure activity relationships of nanovaccines by varying spatial arrangements of lipid and T-helper epitope. The combination of lipid and nanoparticles had a synergistic effect on the stimulation of immune responses against peptide antigens. We also found out the optimum length of polyglutamic acid into the conjugates and used more cationic fungal TMC into the formulation to check its effect on the immunogenicity of nanovaccines. Thus, we developed peptide-based nanovaccines by inducing desired charge (negative) on the antigenic peptide through conjugation strategy and formulating the conjugate with the oppositely charged (positive) polymer through complexation. This self-adjuvanting delivery system may serve as a choice for the design of peptide-based vaccines against variety of pathogens.