title: Nanodisc-incorporated hemagglutinin provides protective immunity against influenza virus infection.
abstract: Every year, influenza virus infection causes significant mortality and morbidity in human populations. Although egg-based inactivated viral vaccines are available, their effectiveness depends on the correct prediction of the circulating viral strains and is limited by the time constraint of the manufacturing process. Recombinant subunit vaccines are easier to manufacture with a relatively short lead time but are limited in their efficacy partly because the purified recombinant membrane proteins in the soluble form most likely do not retain their native membrane-bound structure. Nanodisc (ND) particles are soluble, stable, and reproducibly prepared discoid shaped nanoscale structures that contain a discrete lipid bilayer bound by two amphipathic scaffold proteins. Because ND particles permit the functional reconstitution of membrane/envelope proteins, we incorporated recombinant hemagglutinin (HA) from influenza virus strain A/New Caledonia/20/99 (H1N1) into NDs and investigated their potential to elicit an immune response to HA and confer immunity to influenza virus challenge relative to the commercial vaccines Fluzone and FluMist. HA-ND vaccination induced a robust anti-HA antibody response consisting of predominantly the immunoglobulin G1 (IgG1) subclass and a high hemagglutination inhibition titer. Intranasal immunization with HA-ND induced an anti-HA IgA response in nasal passages. HA-ND vaccination conferred protection that was comparable to that of Fluzone and FluMist against challenge with influenza virus strain A/Puerto Rico/8/1934 (H1N1).
authors.affiliation: Department of Microbiology and Immunology, University of Illinois, Chicago, IL 60612, USA.
authors.forename: Palash
authors.initials: P
authors.lastname: Bhattacharya
authors.forename: Steve
authors.initials: S
authors.lastname: Grimme
authors.forename: Balaji
authors.initials: B
authors.lastname: Ganesh
authors.forename: Anupama
authors.initials: A
authors.lastname: Gopisetty
authors.forename: Jian Rong
authors.initials: JR
authors.lastname: Sheng
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Martinez
authors.forename: Shankar
authors.initials: S
authors.lastname: Jayarama
authors.forename: Michael
authors.initials: M
authors.lastname: Artinger
authors.forename: Matthew
authors.initials: M
authors.lastname: Meriggioli
authors.forename: Bellur S
authors.initials: BS
authors.lastname: Prabhakar
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D056724:Immunity, Humoral; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D008565:Membrane Proteins / Q000627:therapeutic use; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D010743:Phospholipids / Q000627:therapeutic use
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D008565:Membrane Proteins; D010743:Phospholipids