Publication

A direct contact pig influenza challenge model for assessing protective efficacy of monoclonal antibodies

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Last modified
  • 06/25/2025
Type of Material
Authors
    Adam McNee, The Pirbright InstituteDaryll Vanouver, Emory UniversityPramila Rijal, University of OxfordBasudev Paudyal, The Pirbright InstituteFabian Z.X. Lean, Animal and Plant Health Agency-WeybridgeRonan MacLoughlin, Aerogen Ltd.Alejandro Núñez, Animal and Plant Health Agency-WeybridgeAlain Townsend, University of OxfordPhilip John Santangelo, Emory UniversityElma Tchilian, The Pirbright Institute
Language
  • English
Date
  • 2023-10-27
Publisher
  • Frontiers
Publication Version
Copyright Statement
  • © 2023 McNee, Vanover, Rijal, Paudyal, Lean, MacLoughlin, Núñez, Townsend, Santangelo and Tchilian
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Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 14
Start Page
  • 1229051
Grant/Funding Information
  • This work was supported by the Bill and Melinda Gates Foundation INV-032072 and UKRI Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme and Core Capability Grants to The Pirbright Institute BB/X011038/1 and BB/CCG2250/1.
Supplemental Material (URL)
Abstract
  • Monoclonal antibodies (mAbs) can be used to complement immunization for the therapy of influenza virus infection. We have established the pig, a natural large animal host for influenza A, with many physiological, immunological, and anatomical similarities to humans, as an appropriate model for testing mAbs. We have evaluated the protective efficacy of the strongly neutralizing human anti-hemagglutinin mAb, 2-12C in the pig influenza model. Intravenous administration of recombinant 2-12C reduced virus load and lung pathology, however, it did not prevent virus nasal shedding and, consequently, transmission. This may be because the pigs were directly infected intranasally with a high dose of the H1N1pdm09 virus. To address this, we developed a contact challenge model in which the animals were given 2-12C and one day later co-housed with donor pigs previously infected intra-nasally with H1N1pdm09. 2-12C pre-treatment completely prevented infection. We also administered a lower dose of 2-12C by aerosol to the respiratory tract, but this did not prevent shedding in the direct challenge model, although it abolished lung infection. We propose that the direct contact challenge model of pig influenza may be useful for evaluating candidate mAbs and emerging delivery platforms prior to clinical trials.
Author Notes
  • Correspondence: Elma Tchilian, elma.tchilian@pirbright.ac.uk, Present addresses: Adam McNee, Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom; Fabian Z. X. Lean, Department of Pathobiology and Population Sciences, Royal Veterinary College, North Mymms, United Kingdom
Keywords
Research Categories
  • Health Sciences, Immunology

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