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Establishment of a Pig Influenza Challenge Model for Evaluation of Monoclonal Antibody Delivery Platforms

mAbs are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However, questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to...

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Autores principales: McNee, Adam, Smith, Trevor R. F., Holzer, Barbara, Clark, Becky, Bessell, Emily, Guibinga, Ghiabe, Brown, Heather, Schultheis, Katherine, Fisher, Paul, Ramos, Stephanie, Nunez, Alejandro, Bernard, Matthieu, Graham, Simon, Martini, Veronica, Chrun, Tiphany, Xiao, Yongli, Kash, John C., Taubenberger, Jeffery K., Elliott, Sarah, Patel, Ami, Beverley, Peter, Rijal, Pramila, Weiner, David B., Townsend, Alain, Broderick, Kate E., Tchilian, Elma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AAI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372317/
https://www.ncbi.nlm.nih.gov/pubmed/32591390
http://dx.doi.org/10.4049/jimmunol.2000429
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author McNee, Adam
Smith, Trevor R. F.
Holzer, Barbara
Clark, Becky
Bessell, Emily
Guibinga, Ghiabe
Brown, Heather
Schultheis, Katherine
Fisher, Paul
Ramos, Stephanie
Nunez, Alejandro
Bernard, Matthieu
Graham, Simon
Martini, Veronica
Chrun, Tiphany
Xiao, Yongli
Kash, John C.
Taubenberger, Jeffery K.
Elliott, Sarah
Patel, Ami
Beverley, Peter
Rijal, Pramila
Weiner, David B.
Townsend, Alain
Broderick, Kate E.
Tchilian, Elma
author_facet McNee, Adam
Smith, Trevor R. F.
Holzer, Barbara
Clark, Becky
Bessell, Emily
Guibinga, Ghiabe
Brown, Heather
Schultheis, Katherine
Fisher, Paul
Ramos, Stephanie
Nunez, Alejandro
Bernard, Matthieu
Graham, Simon
Martini, Veronica
Chrun, Tiphany
Xiao, Yongli
Kash, John C.
Taubenberger, Jeffery K.
Elliott, Sarah
Patel, Ami
Beverley, Peter
Rijal, Pramila
Weiner, David B.
Townsend, Alain
Broderick, Kate E.
Tchilian, Elma
author_sort McNee, Adam
collection PubMed
description mAbs are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However, questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing mAbs. We show that a strongly neutralizing mAb (2–12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2–12C or a DNA plasmid–encoded version of 2–12C reduced pathology and viral load in the lungs but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate mAbs and emerging delivery platforms prior to human trials.
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spelling pubmed-73723172020-07-23 Establishment of a Pig Influenza Challenge Model for Evaluation of Monoclonal Antibody Delivery Platforms McNee, Adam Smith, Trevor R. F. Holzer, Barbara Clark, Becky Bessell, Emily Guibinga, Ghiabe Brown, Heather Schultheis, Katherine Fisher, Paul Ramos, Stephanie Nunez, Alejandro Bernard, Matthieu Graham, Simon Martini, Veronica Chrun, Tiphany Xiao, Yongli Kash, John C. Taubenberger, Jeffery K. Elliott, Sarah Patel, Ami Beverley, Peter Rijal, Pramila Weiner, David B. Townsend, Alain Broderick, Kate E. Tchilian, Elma J Immunol Immunotherapy and Vaccines mAbs are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However, questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing mAbs. We show that a strongly neutralizing mAb (2–12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2–12C or a DNA plasmid–encoded version of 2–12C reduced pathology and viral load in the lungs but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate mAbs and emerging delivery platforms prior to human trials. AAI 2020-08-01 2020-07-17 /pmc/articles/PMC7372317/ /pubmed/32591390 http://dx.doi.org/10.4049/jimmunol.2000429 Text en Copyright © 2020 The Authors https://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the CC BY 4.0 Unported license.
spellingShingle Immunotherapy and Vaccines
McNee, Adam
Smith, Trevor R. F.
Holzer, Barbara
Clark, Becky
Bessell, Emily
Guibinga, Ghiabe
Brown, Heather
Schultheis, Katherine
Fisher, Paul
Ramos, Stephanie
Nunez, Alejandro
Bernard, Matthieu
Graham, Simon
Martini, Veronica
Chrun, Tiphany
Xiao, Yongli
Kash, John C.
Taubenberger, Jeffery K.
Elliott, Sarah
Patel, Ami
Beverley, Peter
Rijal, Pramila
Weiner, David B.
Townsend, Alain
Broderick, Kate E.
Tchilian, Elma
Establishment of a Pig Influenza Challenge Model for Evaluation of Monoclonal Antibody Delivery Platforms
title Establishment of a Pig Influenza Challenge Model for Evaluation of Monoclonal Antibody Delivery Platforms
title_full Establishment of a Pig Influenza Challenge Model for Evaluation of Monoclonal Antibody Delivery Platforms
title_fullStr Establishment of a Pig Influenza Challenge Model for Evaluation of Monoclonal Antibody Delivery Platforms
title_full_unstemmed Establishment of a Pig Influenza Challenge Model for Evaluation of Monoclonal Antibody Delivery Platforms
title_short Establishment of a Pig Influenza Challenge Model for Evaluation of Monoclonal Antibody Delivery Platforms
title_sort establishment of a pig influenza challenge model for evaluation of monoclonal antibody delivery platforms
topic Immunotherapy and Vaccines
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372317/
https://www.ncbi.nlm.nih.gov/pubmed/32591390
http://dx.doi.org/10.4049/jimmunol.2000429
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