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Immunogenicity of modified vaccinia virus Ankara expressing the hemagglutinin stalk domain of pandemic (H1N1) 2009 influenza virus

tetano

Editor, Senior Moderator
Pathog Glob Health. 2017 Jan 12:1-7. doi: 10.1080/20477724.2016.1275464. [Epub ahead of print]
[h=1]Immunogenicity of modified vaccinia virus Ankara expressing the hemagglutinin stalk domain of pandemic (H1N1) 2009 influenza virus.[/h] Di Mario G[SUP]1[/SUP], Soprana E[SUP]2[/SUP], Gubinelli F[SUP]2[/SUP], Panigada M[SUP]2[/SUP], Facchini M[SUP]1[/SUP], Fabiani C[SUP]1[/SUP], Garulli B[SUP]3[/SUP], Basileo M[SUP]4[/SUP], Cassone A[SUP]4[/SUP], Siccardi A[SUP]2[/SUP], Donatelli I[SUP]1[/SUP], Castrucci MR[SUP]1[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Vaccination offers protection against influenza, although current vaccines need to be reformulated each year. The development of a broadly protective influenza vaccine would guarantee the induction of heterosubtypic immunity also against emerging influenza viruses of a novel subtype. Vaccine candidates based on the stalk region of the hemagglutinin (HA) have the potential to induce broad and persistent protection against diverse influenza A viruses.
[h=4]METHODS:[/h] Modified vaccinia virus Ankara (MVA) expressing a headless HA (hlHA) of A/California/4/09 (CA/09) virus was used as a vaccine to immunize C57BL/6 mice. Specific antibody and cell-mediated immune responses were determined, and challenge experiments were performed by infecting vaccinated mice with CA/09 virus.
[h=4]RESULTS:[/h] Immunization of mice with CA/09-derived hlHA, vectored by MVA, was able to elicit influenza-specific broad cross-reactive antibodies and cell-mediated immune responses, but failed to induce neutralizing antibodies and did not protect mice against virus challenge.
[h=4]CONCLUSION:[/h] Although highly immunogenic, our vaccine was unable to induce a protective immunity against influenza. A misfolded and unstable conformation of the hlHA molecule may have affected its capacity of inducing neutralizing antiviral, conformational antibodies. Design of stable hlHA-based immunogens and their delivery by recombinant MVA-based vectors has the potential of improving this promising approach for a universal influenza vaccine.


[h=4]KEYWORDS:[/h] Influenza virus; MVA vector; antibodies; vaccine

PMID: 28081672 DOI: 10.1080/20477724.2016.1275464
[PubMed - as supplied by publisher]
 
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