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The putative suppressing effect of IgG Fc-conjugated hemagglutinin (HA) stalk of influenza virus H7N9 on the neutralizing immunogenicity of Fc-conjuga

tetano

Editor, Senior Moderator
J Gen Virol. 2015 Dec 9. doi: 10.1099/jgv.0.000365. [Epub ahead of print]
[h=1]The putative suppressing effect of IgG Fc-conjugated hemagglutinin (HA) stalk of influenza virus H7N9 on the neutralizing immunogenicity of Fc-conjugated HA head: implication for rational design of HA-based influenza vaccines.[/h] He B[SUP]1[/SUP], Xia S[SUP]2[/SUP], Yu F[SUP]3[/SUP], Fu Y[SUP]4[/SUP], Li W[SUP]5[/SUP], Wang Q[SUP]6[/SUP], Lu L[SUP]7[/SUP], Jiang S[SUP]8[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] The emergence of influenza A H7N9 in infection has posed a great threat to public health globally. Poor immunogenicity of H7N9 hemagglutinin (HA) is a major obstacle to the development of an effective H7N9 vaccine. Here we found that the vaccine containing H7HA head conjugated with IgG Fc induced strong neutralizing antibody responses and protection against H7N9 infection, while the Fc-conjugated H7HA stalk-based vaccine could not induce neutralizing antibodies, although the Fc-conjugated H7HA stalk-immunized mice were partially protected. The vaccines containing the full-length extracellular domain of HA conjugated with Fc and the mixture of H7HA head-Fc plus stalk-Fc induced significantly lower neutralizing antibody and hemagglutination inhibition titers than H7HA head-Fc-based vaccine. These results suggest that H7HA stalk-Fc may have inhibitory effect on the neutralizing immunogenicity of H7HA head-Fc. Therefore, the neutralizing domain(s), such as the receptor-binding domain, in HA head should be kept and the non-neutralizing domain(s) in HA stalk with the ability to potentially suppress the neutralizing immunogenicity of HA head should be removed from the Fc-conjugated HA-based influenza vaccines to increase the neutralizing antibody response.


PMID: 26653217 [PubMed - as supplied by publisher]
 
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