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    A single-shot adenoviral vaccine provides hemagglutinin stalk-mediated protection against heterosubtypic influenza challenge in mice.

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    Author
    Bliss, Carly M
    Freyn, Alec W
    Caniels, Tom G
    Leyva-Grado, Victor H
    Nachbagauer, Raffael
    Sun, Weina
    Tan, Gene S
    Gillespie, Virginia L
    McMahon, Meagan
    Krammer, Florian
    Hill, Adrian V S
    Palese, Peter
    Coughlan, Lynda
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    Date
    2022-01-07
    Journal
    Molecular Therapy
    Publisher
    Elsevier
    Type
    Article
    
    Metadata
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    See at
    https://doi.org/10.1016/j.ymthe.2022.01.011
    Abstract
    Conventional influenza vaccines fail to confer broad protection against diverse influenza A viruses with pandemic potential. Efforts to develop a universal influenza virus vaccine include refocusing immunity towards the highly conserved stalk domain of the influenza virus surface glycoprotein, hemagglutinin (HA). We constructed a non-replicating adenoviral (Ad) vector, encoding a secreted form of H1 HA, to evaluate HA stalk-focused immunity. The Ad5_H1 vaccine was tested in mice for its ability to elicit broad, cross-reactive protection against homologous, heterologous, and heterosubtypic lethal challenge in a single-shot immunization regimen. Ad5_H1 elicited hemagglutination inhibition (HI+) active antibodies (Abs), which conferred 100% sterilizing protection from homologous H1N1 challenge. Furthermore, Ad5_H1 rapidly induced H1-stalk-specific Abs with Fc-mediated effector function activity, in addition to stimulating both CD4+ and CD8+ stalk-specific T cell responses. This phenotype of immunity provided 100% protection from lethal challenge with a head-mismatched, reassortant influenza virus bearing a chimeric HA, cH6/1, in a stalk-mediated manner. Most importantly, 100% protection from mortality following lethal challenge with a heterosubtypic avian influenza virus, H5N1, was observed following a single immunization with Ad5_H1. In conclusion, Ad-based influenza vaccines can elicit significant breadth of protection in naive animals and could be considered for pandemic preparedness and stockpiling.
    Rights/Terms
    Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
    Keyword
    adenoviral
    adenovirus
    hemagglutinin
    heterosubtypic
    immunogenicity
    influenza
    stalk
    stem
    universal vaccine
    vaccine
    vector
    Show allShow less
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/17884
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ymthe.2022.01.011
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