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A single cycle influenza virus coated in H7 haemagglutinin generates neutralizing antibody responses to haemagglutinin and neuraminidase glycoproteins

tetano

Editor, Senior Moderator
J Gen Virol. 2019 Feb 4. doi: 10.1099/jgv.0.001228. [Epub ahead of print]
[h=1]A single cycle influenza virus coated in H7 haemagglutinin generates neutralizing antibody responses to haemagglutinin and neuraminidase glycoproteins and protection from heterotypic challenge.[/h] Powell TJ[SUP]1,[/SUP][SUP]2[/SUP], Rijal P[SUP]2[/SUP], McEwen-Smith RM[SUP]2[/SUP], Byun H[SUP]2[/SUP], Hardwick M[SUP]2[/SUP], Schimanski LM[SUP]2[/SUP], Huang KA[SUP]3[/SUP], Daniels RS[SUP]4[/SUP], Townsend ARM[SUP]2[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] A non-replicating form of pseudotyped influenza virus, inactivated by suppression of the haemagglutinin signal sequence (S-FLU), can act as a broadly protective vaccine. S-FLU can infect for a single round only, and induces heterotypic protection predominantly through activation of cross-reactive T cells in the lung. Unlike the licensed live attenuated virus, it cannot reassort a pandemic haemagglutinin (HA) into seasonal influenza. Here we present data on four new forms of S-FLU coated with H7 HAs from either A/Anhui/1/2013, A/Shanghai/1/2013, A/Netherlands/219/2003 or A/New York/107/2003 strains of H7 virus. We show that intranasal vaccination induced a strong local CD8 T cell response and protected against heterosubtypic X31 (H3N2) virus and highly virulent PR8 (H1N1), but not influenza B virus. Intranasal vaccination also induced a strong neutralizing antibody response to the encoded neuraminidase. If given at higher dose in the periphery with intraperitoneal administration, H7 S-FLU induced a specific neutralizing antibody response to H7 HA coating the particle. Polyvalent intraperitoneal vaccination with mixed H7 S-FLU induced a broadly neutralizing antibody response to all four H7 strains. S-FLU is a versatile vaccine candidate that could be rapidly mobilized ahead of a new pandemic threat.


PMID: 30714896 DOI: 10.1099/jgv.0.001228
 
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