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

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.

• Authors: Carly M Bliss, Alec W Freyn, Tom G Caniels, Victor H Leyva-Grado, Raffael Nachbagauer, Weina Sun, Gene S Tan, Virginia L Gillespie, Meagan McMahon, Florian Krammer, Adrian V S Hill, Peter Palese, Lynda Coughlan
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 30 Issue 5 Pg. 2024-2047 (05 04 2022) ISSN: 1525-0024 [Electronic] United States
• PMID: 34999208 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Viral
• Hemagglutinin Glycoproteins, Influenza Virus
• Hemagglutinins
• Influenza Vaccines

Topics

• Adenoviridae (genetics)
• Animals
• Antibodies, Viral
• Hemagglutinin Glycoproteins, Influenza Virus (genetics)
• Hemagglutinins
• Humans
• Influenza A Virus, H1N1 Subtype
• Influenza A Virus, H5N1 Subtype (genetics)
• Influenza A virus
• Influenza Vaccines
• Influenza, Human (prevention & control)
• Mice
• Mice, Inbred BALB C
• Orthomyxoviridae Infections