An efficient, chemically-defined semisynthetic lipid-adjuvanted nanoparticulate vaccine development system

A novel vaccine development platform that enables the site-specific conjugation of synthetic lipid adjuvants to recombinant proteins was produced. This technology facilitates the simple and efficient production of homogeneous, chemically-defined, semisynthetic lipoprotein vaccines. Using a polytope ‘string-of-beads’ approach, a synthetic gene incorporating seven Streptococcus pyogenes M protein strain-specific antigens, and a conserved M protein antigen (J14) was produced, expressed, and attached to a lipoamino acid based adjuvant (lipid core peptide; LCP). Nanoparticles (40 nm diameter) of an optimal size for stimulating antibody-mediated immunity were formed upon the addition of these lipoproteins to aqueous buffer (PBS). Systemic antigen-specific IgG antibodies were raised against all eight antigens in C57BL/6 J mice, without the need to formulate with additional adjuvant. These antibodies bound cell surface M proteins of S. pyogenes strains represented within the polytope sequence, with higher antibody levels observed where a dendritic cell targeting peptide (DCpep) was incorporated within the LCP adjuvant.From the Clinical EditorIn this study, a novel vaccine development system is presented, combining adjuvants with recombinant protein antigens, and presenting the antigen in a nanoparticle system optimized for antibody production. They demonstrate efficient vaccination in a murine model system without the need for additional adjuvants.

Graphical AbstractA vaccine delivery platform was produced that enables the site-specific conjugation of a synthetic lipid-based adjuvant (lipid core peptide; LCP) with recombinant antigens. The products of this technology incorporate adjuvant, antigen, and dendritic cell targeting into a chemically defined semisynthetic construct. Model vaccines incorporating eight group A streptococcal (GAS) M protein antigens were developed, which formed nanoparticles (~ 40 nm) upon their addition to PBS. Administration of these nanoparticles to C57BL/6 J mice, without additional adjuvant, lead to the production of systemic IgG antibodies targeting all eight antigens, which bound M proteins from GAS strains represented within the recombinant antigen sequence.Figure optionsDownload high-quality image (146 K)Download as PowerPoint slide