Colocalized delivery of adjuvant and antigen using nanolipoprotein particles enhances the immune response to recombinant antigens

J Am Chem Soc. 2013 Feb 13;135(6):2044-7. doi: 10.1021/ja3063293. Epub 2013 Jan 31.

Abstract

Subunit antigen-based vaccines can provide a number of important benefits over traditional vaccine candidates, such as overall safety. However, because of the inherently low immunogenicity of these antigens, methods for colocalized delivery of antigen and immunostimulatory molecules (i.e., adjuvants) are needed. Here we report a robust nanolipoprotein particle (NLP)-based vaccine delivery platform that facilitates the codelivery of both subunit antigens and adjuvants. Ni-chelating NLPs (NiNLPs) were assembled to incorporate the amphipathic adjuvants monophosphoryl lipid A and cholesterol-modified CpG oligodeoxynucleotides, which can bind His-tagged protein antigens. Colocalization of antigen and adjuvant delivery using the NiNLP platform resulted in elevated antibody production against His-tagged influenza hemagglutinin 5 and Yersinia pestis LcrV antigens. Antibody titers in mice immunized with the adjuvanted NLPs were 5-10 times higher than those observed with coadministration formulations and nonadjuvanted NiNLPs. Colocalized delivery of adjuvant and antigen provides significantly greater immune stimulation in mice than coadministered formulations.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adjuvants, Immunologic / chemistry*
  • Animals
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / immunology*
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Lipoproteins / chemistry*
  • Lipoproteins / immunology
  • Mice
  • Nanoparticles / chemistry*
  • Nickel / chemistry
  • Nickel / immunology
  • Pore Forming Cytotoxic Proteins / chemistry
  • Pore Forming Cytotoxic Proteins / immunology*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Vaccines / chemistry*
  • Vaccines / immunology

Substances

  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • Hemagglutinin Glycoproteins, Influenza Virus
  • LcrV protein, Yersinia
  • Lipoproteins
  • Pore Forming Cytotoxic Proteins
  • Recombinant Proteins
  • Vaccines
  • hemagglutinin, avian influenza A virus
  • Nickel