Protective porcine influenza virus-specific monoclonal antibodies recognize similar haemagglutinin epitopes as humans

Barbara Holzer, Pramila Rijal, Adam McNee, Basudev Paudyal, Veronica Martini, Becky Clark, Tanuja Manjegowda, Francisco Javier Salguero Bodes, Emily Bessell, John C. Schwartz, Katy Moffat, Miriam Pedrera, Simon P. Graham, Alistair Noble, Marie Bonnet-Di Placido, Roberto M. La Ragione, William Mwangi, Peter Beverley, John W. McCauley, Rodney S. DanielsJohn A. Hammond, Alain R. Townsend, Elma Tchilian

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Abstract

Pigs are natural hosts for the same subtypes of influenza A viruses as humans and integrally involved in virus evolution with frequent interspecies transmissions in both directions. The emergence of the 2009 pandemic H1N1 virus illustrates the importance of pigs in evolution of zoonotic strains. Here we generated pig influenza-specific monoclonal antibodies (mAbs) from H1N1pdm09 infected pigs. The mAbs recognized the same two major immunodominant haemagglutinin (HA) epitopes targeted by humans, one of which is not recognized by post-infection ferret antisera that are commonly used to monitor virus evolution. Neutralizing activity of the pig mAbs was comparable to that of potent human anti-HA mAbs. Further, prophylactic administration of a selected porcine mAb to pigs abolished lung viral load and greatly reduced lung pathology but did not eliminate nasal shedding of virus after H1N1pdm09 challenge. Hence mAbs from pigs, which target HA can significantly reduce disease severity. These results, together with the comparable sizes of pigs and humans, indicate that the pig is a valuable model for understanding how best to apply mAbs as therapy in humans and for monitoring antigenic drift of influenza viruses in humans, thereby providing information highly relevant to making influenza vaccine recommendations.

Original languageEnglish
Article number1009330
Number of pages25
JournalPLoS Pathogens
Volume17
Issue number3
DOIs
Publication statusPublished - 4 Mar 2021

Bibliographical note

Funding Information: This work was supported by Bill & Melinda Gates Foundation grant OPP1201470 to ET, AM, BH, BC, EB and OPP1215550 to JH, ET, SG, BP, JS, MP, SG, MBP, AN, WM (Pirbright Livestock Antibody Hub); ET, SG, JH, BP, BC, TM, EB, KM, MP, WM were funded by UKRI Biotechnology and Biological Sciences Research Council (BBSRC) grants: BBS/E/I/00007031, BBS/E/I/00007038 and BBS/E/I/00007039. P.R. and A.R.T. were funded by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS), China Grant 2018-I2M-2-002, the Townsend-Jeantet Prize Charitable Trust (charity number 1011770) and the Medical Research Council (MRC) Grant MR/P021336/1. RR was funded by the MRC, BBSRC, EU and ESPRC(IAA). The work done at the Crick Worldwide Influenza Centre by JM and RD was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001030), the Medical Research Council (FC001030) and the Wellcome Trust (FC001030). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Open Access: This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publisher Copyright: © 2021 Holzer et al.

Citation: Holzer B, Rijal P, McNee A, Paudyal B, Martini V, Clark B, et al. (2021) Protective porcine influenza virus-specific monoclonal antibodies recognize similar haemagglutinin epitopes as humans. PLoS Pathog 17(3): e1009330.

DOI: https://doi.org/10.1371/journal.ppat.1009330

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