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Jun 06, 2013
 |  BC Innovations  |  Targets & Mechanisms

Nanoparticles for the flu

An NIH team has created a self-assembling influenza nanoparticle that induces the production of antibodies against a wider range of flu strains than traditional vaccines.1 The team hopes to test the immunogenicity of the vaccine in humans once a GMP manufacturing process is developed.

The nanoparticle consists of a fusion of the influenza A virus hemagglutinin (HA) from New Caledonia H1N1 1999 strain and ferritin, an iron-storage protein from Helicobacter pylori.

Ferritin self-assembles into nanoparticles, and previous work has shown nanoparticles made up of 24 ferritin monomers could be used to display 24 peptides on the capsid surface by engineering an N-terminal fusion peptide with ferritin. The researchers used the peptide-ferritin nanoparticles in rats to generate high titers of antibody to an HIV Tat protein antigen.2

The NIH team hypothesized that the spacing between the ferritin units in the nanoparticle could yield HA proteins in the form of spike-like trimers that would mimic exactly the presentation of the protein on the surface of the influenza virus.

The group expressed the HA-ferritin fusion protein in mammalian cells and showed using electron microscopy that the self-assembled spherical nanoparticle presented eight trimeric viral spikes. To confirm the antigenicity of the HA trimer, the group showed that two mAbs against the H1N1 New Caledonia 1999 HA-one against the stem and one against the head-bound to the HA-ferritin nanoparticle.

In mice, an adjuvant plus the HA-ferritin nanoparticle led to about seven times more neutralizing antibodies than adjuvant plus a conventional trivalent inactivated influenza vaccine containing the same strain.

The HA-ferritin vaccine also induced broadly neutralizing antibodies that cross-reacted with mismatched virus.

The team then used the strategy to create...

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