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

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 VS., Palese, Peter and Coughlan, Lynda 2022. A single-shot adenoviral vaccine provides hemagglutinin stalk-mediated protection against heterosubtypic influenza challenge in mice. Molecular Therapy 30 (5) , pp. 2024-2047. 10.1016/j.ymthe.2022.01.011

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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 naïve animals and could be considered for pandemic preparedness and stockpiling.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Publisher:	Cell Press
ISSN:	1525-0016
Date of First Compliant Deposit:	20 January 2022
Date of Acceptance:	5 January 2022
Last Modified:	02 May 2023 18:44
URI:	https://orca.cardiff.ac.uk/id/eprint/146715

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