title: Colocalized delivery of adjuvant and antigen using nanolipoprotein particles enhances the immune response to recombinant antigens.
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.
authors: Physical and Life Sciences, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
authors: Nicholas O
authors: NO
authors: Fischer
authors: Amy
authors: A
authors: Rasley
authors: Michele
authors: M
authors: Corzett
authors: Mona H
authors: MH
authors: Hwang
authors: Paul D
authors: PD
authors: Hoeprich
authors: Craig D
authors: CD
authors: Blanchette
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000276:immunology*; D008074:Lipoproteins / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009532:Nickel / Q000737:chemistry / Q000276:immunology; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D014612:Vaccines / Q000737:chemistry* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C043908:LcrV protein, Yersinia; D008074:Lipoproteins; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins; D014612:Vaccines; C109963:hemagglutinin, avian influenza A virus; D009532:Nickel