Immunization with matrix-, nucleoprotein and neuraminidase protects against H3N2 influenza challenge in pH1N1 pre-exposed pigs

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Abstract

There is an urgent need for influenza vaccines providing broader protection that may decrease the need for annual immunization of the human population. We investigated the efficacy of heterologous prime boost immunization with chimpanzee adenovirus (ChAdOx2) and modified vaccinia Ankara (MVA) vectored vaccines, expressing conserved influenza virus nucleoprotein (NP), matrix protein 1 (M1) and neuraminidase (NA) in H1N1pdm09 pre-exposed pigs. We compared the efficacy of intra-nasal, aerosol and intra-muscular vaccine delivery against H3N2 influenza challenge. Aerosol prime boost immunization induced strong local lung T cell and antibody responses and abrogated viral shedding and lung pathology following H3N2 challenge. In contrast, intramuscular immunization induced powerful systemic responses and weak local lung responses but also abolished lung pathology and reduced viral shedding. These results provide valuable insights into the development of a broadly protective influenza vaccine in a highly relevant large animal model and will inform future vaccine and clinical trial design.

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Author and article information

Contributors

Eleni Vatzia:

ORCID: http://orcid.org/0000-0002-2864-4962

eleni.vatzia@pirbright.ac.uk

Elma Tchilian:

ORCID: http://orcid.org/0000-0002-4869-5118

elma.tchilian@pirbright.ac.uk

Journal

Journal ID (nlm-ta): NPJ Vaccines

Journal ID (iso-abbrev): NPJ Vaccines

Title: NPJ Vaccines

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2059-0105

Publication date (Electronic): 15 February 2023

Publication date PMC-release: 15 February 2023

Publication date Collection: 2023

Volume: 8

Electronic Location Identifier: 19

Affiliations

[1 ]GRID grid.63622.33, ISNI 0000 0004 0388 7540, The Pirbright Institute, ; Pirbright, United Kingdom

[2 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Nuffield Department of Medicine, University of Oxford, ; Oxford, United Kingdom

[3 ]GRID grid.422685.f, ISNI 0000 0004 1765 422X, Animal and Plant Health Agency-Weybridge, New Haw, ; Addlestone, United Kingdom

[4 ]GRID grid.508890.c, ISNI 0000 0004 6007 2153, Aerogen Ltd, ; Galway, Ireland

[5 ]United Kingdom Health Security Agency, UKHSA-Porton Down, Salisbury, United Kingdom

[6 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Oxford Vaccine Group, Department of Paediatrics, Medical Sciences Division, University of Oxford and Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, ; Oxford, United Kingdom

Author information

Eleni Vatzia http://orcid.org/0000-0002-2864-4962

Helen E. Everett http://orcid.org/0000-0002-1233-4265

Ronan MacLoughlin http://orcid.org/0000-0002-3164-1607

Sarah C. Gilbert http://orcid.org/0000-0002-6823-9750

Elma Tchilian http://orcid.org/0000-0002-4869-5118

Article

Publisher ID: 620

DOI: 10.1038/s41541-023-00620-2

PMC ID: 9930017

PubMed ID: 36792640

SO-VID: 1e65400e-f0fe-429a-b030-efbce1a0c0e4

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 13 September 2022

Date accepted : 30 January 2023

Funding

Funded by: FundRef https://doi.org/10.13039/501100000265, RCUK | Medical Research Council (MRC);

Award ID: MR/S037160/1

Award Recipient : Eleni Vatzia Katherine Feest Adam McNee Tanuja Manjegowda B. Veronica Carr Basudev Paudyal Tiphany Chrun Emmanuel A. Maze Amy Mccarron Susan Morris Helen E. Everett Ronan MacLoughlin Francisco J. Salguero Teresa Lambe Sarah C. Gilbert Elma Tchilian

Funded by: FundRef https://doi.org/10.13039/501100000870, Pirbright Institute;

Award ID: BBS/E/I/00007031

Award ID: BBS/E/I/00007037

Award ID: BBS/E/I/00007039

Award ID: BBS/E/I/00007031

Award ID: BBS/E/I/00007037

Award ID: BBS/E/I/00007039

Award ID: BBS/E/I/00007031

Award ID: BBS/E/I/00007037

Award ID: BBS/E/I/00007039

Award ID: BBS/E/I/00007031

Award ID: BBS/E/I/00007037

Award ID: BBS/E/I/00007039

Award ID: BBS/E/I/00007031

Award ID: BBS/E/I/00007037

Award ID: BBS/E/I/00007039

Award ID: BBS/E/I/00007031

Award ID: BBS/E/I/00007037

Award ID: BBS/E/I/00007039

Award ID: BBS/E/I/00007031

Award ID: BBS/E/I/00007037

Award ID: BBS/E/I/00007039

Award ID: BBS/E/I/00007031

Award ID: BBS/E/I/00007037

Award ID: BBS/E/I/00007039

Award ID: BBS/E/I/00007031

Award ID: BBS/E/I/00007037

Award ID: BBS/E/I/00007039

Award Recipient : Eleni Vatzia Katherine Feest Adam McNee Tanuja Manjegowda B. Veronica Carr Basudev Paudyal Tiphany Chrun Emmanuel A. Maze Elma Tchilian