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

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

doi:10.1038/s41541-023-00620-2

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

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^*

^*Corresponding author for this work

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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.

Original language	English
Article number	19
Journal	npj Vaccines
Volume	8
DOIs	https://doi.org/10.1038/s41541-023-00620-2
Publication status	Published - 15 Feb 2023

Bibliographical note

Funding Information: This work was supported by the Medical Research Council (grant number MR/S037160/1) and UKRI Biotechnology and Biological Sciences Research Council (BBSRC). Institute Strategic Programme and Core Capability Grants to The Pirbright Institute (BBS/E/I/00007031 and BBS/E/I/00007037 and BBS/E/I/00007039). The authors would also like to acknowledge the Pirbright Flow Cytometry facility and support through the Core capability grant (BBS/E/I/00007039).

The authors declare the following competing financial interests: S.C.G. is co-founder of Vaccitech and named as an inventor on a patent covering use of ChAdOx2-vectored vaccines. T.L. is a consultant to Vaccitech. RM is an employee of Aerogen Limited.

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/.

Publisher Copyright: © The Author(s) 2023

Citation: Vatzia, E., Feest, K., McNee, A. et al. Immunization with matrix-, nucleoprotein and neuraminidase protects against H3N2 influenza challenge in pH1N1 pre-exposed pigs. npj Vaccines 8, 19 (2023). https://doi.org/10.1038/s41541-023-00620-2

DOI: https://doi.org/10.1038/s41541-023-00620-2

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Vatzia2023ImmunizationWithMatrixNucleoproteinAndNeuraminidaseProtectsAgainstH3N2InfluenzanpjVaccinesFinal published version, 2.82 MBLicence: CC BY

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Vatzia, E., Feest, K., McNee, A., Manjegowda, T., Carr, B. V., Paudyal, B., Chrun, T., Maze, E. A., Mccarron, A., Morris, S., Everett, H. E., MacLoughlin, R., Salguero, F. J., Lambe, T., Gilbert, S. C., & Tchilian, E. (2023). Immunization with matrix-, nucleoprotein and neuraminidase protects against H3N2 influenza challenge in pH1N1 pre-exposed pigs. npj Vaccines, 8, Article 19. https://doi.org/10.1038/s41541-023-00620-2

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

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.",

author = "Eleni Vatzia and Katherine Feest and Adam McNee and Tanuja Manjegowda and Carr, \{B. Veronica\} and Basudev Paudyal and Tiphany Chrun and Maze, \{Emmanuel A.\} and Amy Mccarron and Susan Morris and Everett, \{Helen E.\} and Ronan MacLoughlin and Salguero, \{Francisco J.\} and Teresa Lambe and Gilbert, \{Sarah C.\} and Elma Tchilian",

note = "Funding Information: This work was supported by the Medical Research Council (grant number MR/S037160/1) and UKRI Biotechnology and Biological Sciences Research Council (BBSRC). Institute Strategic Programme and Core Capability Grants to The Pirbright Institute (BBS/E/I/00007031 and BBS/E/I/00007037 and BBS/E/I/00007039). The authors would also like to acknowledge the Pirbright Flow Cytometry facility and support through the Core capability grant (BBS/E/I/00007039). The authors declare the following competing financial interests: S.C.G. is co-founder of Vaccitech and named as an inventor on a patent covering use of ChAdOx2-vectored vaccines. T.L. is a consultant to Vaccitech. RM is an employee of Aerogen Limited. 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{\textquoteright}s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article{\textquoteright}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/. Publisher Copyright: {\textcopyright} The Author(s) 2023 Citation: Vatzia, E., Feest, K., McNee, A. et al. Immunization with matrix-, nucleoprotein and neuraminidase protects against H3N2 influenza challenge in pH1N1 pre-exposed pigs. npj Vaccines 8, 19 (2023). https://doi.org/10.1038/s41541-023-00620-2 DOI: https://doi.org/10.1038/s41541-023-00620-2",

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Vatzia, E, Feest, K, McNee, A, Manjegowda, T, Carr, BV, Paudyal, B, Chrun, T, Maze, EA, Mccarron, A, Morris, S, Everett, HE, MacLoughlin, R, Salguero, FJ, Lambe, T, Gilbert, SC & Tchilian, E 2023, 'Immunization with matrix-, nucleoprotein and neuraminidase protects against H3N2 influenza challenge in pH1N1 pre-exposed pigs', npj Vaccines, vol. 8, 19. https://doi.org/10.1038/s41541-023-00620-2

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T1 - Immunization with matrix-, nucleoprotein and neuraminidase protects against H3N2 influenza challenge in pH1N1 pre-exposed pigs

AU - Vatzia, Eleni

AU - Feest, Katherine

AU - McNee, Adam

AU - Manjegowda, Tanuja

AU - Carr, B. Veronica

AU - Paudyal, Basudev

AU - Chrun, Tiphany

AU - Maze, Emmanuel A.

AU - Mccarron, Amy

AU - Morris, Susan

AU - Everett, Helen E.

AU - MacLoughlin, Ronan

AU - Salguero, Francisco J.

AU - Lambe, Teresa

AU - Gilbert, Sarah C.

AU - Tchilian, Elma

N1 - Funding Information: This work was supported by the Medical Research Council (grant number MR/S037160/1) and UKRI Biotechnology and Biological Sciences Research Council (BBSRC). Institute Strategic Programme and Core Capability Grants to The Pirbright Institute (BBS/E/I/00007031 and BBS/E/I/00007037 and BBS/E/I/00007039). The authors would also like to acknowledge the Pirbright Flow Cytometry facility and support through the Core capability grant (BBS/E/I/00007039). The authors declare the following competing financial interests: S.C.G. is co-founder of Vaccitech and named as an inventor on a patent covering use of ChAdOx2-vectored vaccines. T.L. is a consultant to Vaccitech. RM is an employee of Aerogen Limited. 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/. Publisher Copyright: © The Author(s) 2023 Citation: Vatzia, E., Feest, K., McNee, A. et al. Immunization with matrix-, nucleoprotein and neuraminidase protects against H3N2 influenza challenge in pH1N1 pre-exposed pigs. npj Vaccines 8, 19 (2023). https://doi.org/10.1038/s41541-023-00620-2 DOI: https://doi.org/10.1038/s41541-023-00620-2

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

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