Design and Synthesis of Lipopeptide-Carbohydrate Assembled Multivalent Vaccine Candidates Using Native Chemical Ligation

Development of a synthetic vaccine against group A streptococcal infection is increasingly paramount due to the induction of autoimmunity by the main virulent factor - M protein. Peptide vaccines, however, are generally poorly immunogenic, necessitating administration with carriers and adjuvants. One of the promising approaches to deliver antigenic peptides is to assemble peptides on a suitable template which directs the attached peptides to forma well defined tertiary structure. For self-adjuvanting human vaccines, the conjugation of immunostimulatory lipids has been demonstrated as a potentially safe method. This study describes the design and optimized synthesis of two lipopeptide conjugated carbohydrate templates and the assembling of peptide antigens. These lipopeptide-carbohydrate assembled multivalent vaccine candidates were obtained in high yield and purity when native chemical ligation was applied. Circular dichroism studies indicated that the template-assembled peptides form four alpha-helix bundles. The developed technique extends the use of carbohydrate templates and lipopeptide conjugates for producing self-adjuvanting and topology-controlled vaccine candidates.