Bhattacharya P, Grimme S, Ganesh B, Gopisetty A, Sheng JR, Martinez O, Jayarama S, Artinger M, Meriggioli M, Prabhakar BS
Nanodisc incorporated hemagglutinin provides protective immunity against influenza virus infection. [JOURNAL ARTICLE]
J Virol 2009 Oct 14.
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(R) (ND) particles are soluble, stable and reproducibly prepared discoidal shaped nanoscale structures that contain a discrete lipid bilayer bound by two amphipathic scaffold proteins. Because Nanodisc particles permit functional reconstitution of membrane/envelope proteins, we incorporated recombinant hemagglutinin (HA) from influenza virus A H1N1/New Caledonia/20/99 strain into Nanodiscs and investigated their potential to elicit an immune response to HA and confer immunity to influenza virus challenge relative to the commercial vaccines Fluzone(R) and FluMist(R). The HA-ND vaccination induced a robust anti-HA antibody response consisting of predominantly IgG1 subclass and a high hemagglutination inhibition titer. Intra nasal 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 H1N1/PR/8/34.
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