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

  • Moyle P
  • Hartas J
  • Henningham A
 et al. 
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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 Editor: 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. © 2013 .

Author-supplied keywords

  • Lipid adjuvants
  • Recombinant proteins
  • Semisynthesis
  • Streptococcus pyogenes
  • Subunit vaccines

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  • Peter M. Moyle

  • Jon Hartas

  • Anna Henningham

  • Michael R. Batzloff

  • Michael F. Good

  • Istvan Toth

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