Conjugation to nickel-chelating nanolipoprotein particles increases the potency and efficacy of subunit vaccines to prevent West Nile encephalitis.
Subunit antigens are attractive candidates for vaccine development, as they are safe, cost-effective, and rapidly produced. Nevertheless, subunit antigens often need to be adjuvanted and/or formulated to produce products with acceptable potency and efficacy. Here, we describe a simple method for improving the potency and efficacy of a recombinant subunit antigen by its immobilization on nickel-chelating nanolipoprotein particles (NiNLPs). NiNLPs are membrane mimetic nanoparticles that provide a delivery and presentation platform amenable to binding any recombinant subunit immunogens featuring a polyhistidine tag. A His-tagged, soluble truncated form of the West Nile virus (WNV) envelope protein (trE-His) was immobilized on NiNLPs. Single inoculations of the NiNLP-trE-His produced superior anti-WNV immune responses and provided significantly improved protection against a live WNV challenge compared to mice inoculated with trE-His alone. These results have broad implications in vaccine development and optimization, as NiNLP technology is well-suited to many types of vaccines, providing a universal platform for enhancing the potency and efficacy of recombinant subunit immunogens.
Lawrence Livermore National Laboratory, Livermore, California 94551, USA.
Nicholas O
NO
Fischer
Ernesto
E
Infante
Tomohiro
T
Ishikawa
Craig D
CD
Blanchette
Nigel
N
Bourne
Paul D
PD
Hoeprich
Peter W
PW
Mason
D000818:Animals; D002614:Chelating Agents / Q000008:administration & dosage / Q000737:chemistry*; D018792:Encephalitis, Viral / Q000276:immunology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D008074:Lipoproteins / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009532:Nickel / Q000737:chemistry*; D013997:Time Factors; D022223:Vaccines, Subunit / Q000737:chemistry / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology; D014901:West Nile Fever / Q000276:immunology / Q000517:prevention & control*; D053060:West Nile Virus Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*
D002614:Chelating Agents; D008074:Lipoproteins; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; D053060:West Nile Virus Vaccines; D009532:Nickel