Intranasal Vaccination with a Lipopeptide Containing a Conformationally Constrained Conserved Minimal Peptide, a Universal T Cell Epitope, and a Self‐Adjuvanting Lipid Protects Mice from Group A Streptococcus Challenge and Reduces Throat Colonization

Infection with group A streptococcus (GAS) may result in a number of human diseases, including potentially life-threatening postinfectious sequelae. In the present study, J14, a conformationally constrained conserved minimal peptide from the M protein, was incorporated into a lipopeptide construct to which a universal T cell epitope and a self-adjuvanting lipid moiety, Pam(2)Cys, were also attached. We demonstrate that this lipopeptide construct, when administered intranasally (inl) without additional adjuvants, protects outbred mice from lethal respiratory GAS challenge. In addition, the lipopeptide was capable of inducing J14-specific mucosal immunoglobulin A, which coincided with reduced throat colonization after respiratory GAS challenge. These preclinical experiments show that this lipopeptide could form the basis of an antidisease and transmission-blocking inl GAS vaccine.