title: An efficient, chemically-defined semisynthetic lipid-adjuvanted nanoparticulate vaccine development system.
abstract: 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/6J 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.
  
  
  BACKGROUND
  In 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.
authors: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia 4072, QLD, Australia; Institute for Molecular Biosciences, The University of Queensland, St Lucia 4072, QLD, Australia. Electronic address: p.moyle@uq.edu.au.
authors: Peter M
authors: PM
authors: Moyle
authors: Jon
authors: J
authors: Hartas
authors: Anna
authors: A
authors: Henningham
authors: Michael R
authors: MR
authors: Batzloff
authors: Michael F
authors: MF
authors: Good
authors: Istvan
authors: I
authors: Toth
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D005455:Fluorescent Antibody Technique; D007109:Immunity; D008055:Lipids / Q000737:chemistry*; D008074:Lipoproteins / Q000737:chemistry; D008301:Maleimides / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D022541:Streptococcal Vaccines / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D008055:Lipids; D008074:Lipoproteins; D008301:Maleimides; D022541:Streptococcal Vaccines
keywords: Lipid adjuvants; Recombinant proteins; Semisynthesis; Streptococcus pyogenes; Subunit vaccines