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Low Dose Pig Anti-Influenza Virus Monoclonal Antibodies Reduce Lung Pathology but Do Not Prevent Virus Shedding

We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing the therapeutic potential of monoclonal antibodies (mAbs). In this study we demonstrated that prophylactic intravenous administration of 15 mg/kg of p...

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Autores principales: Paudyal, Basudev, McNee, Adam, Rijal, Pramila, Carr, B. Veronica, Nunez, Alejandro, McCauley, John, Daniels, Rodney S., Townsend, Alain R., Hammond, John A., Tchilian, Elma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716435/
https://www.ncbi.nlm.nih.gov/pubmed/34975888
http://dx.doi.org/10.3389/fimmu.2021.790918
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author Paudyal, Basudev
McNee, Adam
Rijal, Pramila
Carr, B. Veronica
Nunez, Alejandro
McCauley, John
Daniels, Rodney S.
Townsend, Alain R.
Hammond, John A.
Tchilian, Elma
author_facet Paudyal, Basudev
McNee, Adam
Rijal, Pramila
Carr, B. Veronica
Nunez, Alejandro
McCauley, John
Daniels, Rodney S.
Townsend, Alain R.
Hammond, John A.
Tchilian, Elma
author_sort Paudyal, Basudev
collection PubMed
description We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing the therapeutic potential of monoclonal antibodies (mAbs). In this study we demonstrated that prophylactic intravenous administration of 15 mg/kg of porcine mAb pb18, against the K160–163 site of the hemagglutinin, significantly reduced lung pathology and nasal virus shedding and eliminated virus from the lung of pigs following H1N1pdm09 challenge. When given at 1 mg/kg, pb18 significantly reduced lung pathology and lung and BAL virus loads, but not nasal shedding. Similarly, when pb18 was given in combination with pb27, which recognized the K130 site, at 1 mg/kg each, lung virus load and pathology were reduced, although without an apparent additive or synergistic effect. No evidence for mAb driven virus evolution was detected. These data indicate that intravenous administration of high doses was required to reduce nasal virus shedding, although this was inconsistent and seldom complete. In contrast, the effect on lung pathology and lung virus load is consistent and is also seen at a one log lower dose, strongly indicating that a lower dose might be sufficient to reduce severity of disease, but for prevention of transmission other measures would be needed.
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spelling pubmed-87164352021-12-31 Low Dose Pig Anti-Influenza Virus Monoclonal Antibodies Reduce Lung Pathology but Do Not Prevent Virus Shedding Paudyal, Basudev McNee, Adam Rijal, Pramila Carr, B. Veronica Nunez, Alejandro McCauley, John Daniels, Rodney S. Townsend, Alain R. Hammond, John A. Tchilian, Elma Front Immunol Immunology We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing the therapeutic potential of monoclonal antibodies (mAbs). In this study we demonstrated that prophylactic intravenous administration of 15 mg/kg of porcine mAb pb18, against the K160–163 site of the hemagglutinin, significantly reduced lung pathology and nasal virus shedding and eliminated virus from the lung of pigs following H1N1pdm09 challenge. When given at 1 mg/kg, pb18 significantly reduced lung pathology and lung and BAL virus loads, but not nasal shedding. Similarly, when pb18 was given in combination with pb27, which recognized the K130 site, at 1 mg/kg each, lung virus load and pathology were reduced, although without an apparent additive or synergistic effect. No evidence for mAb driven virus evolution was detected. These data indicate that intravenous administration of high doses was required to reduce nasal virus shedding, although this was inconsistent and seldom complete. In contrast, the effect on lung pathology and lung virus load is consistent and is also seen at a one log lower dose, strongly indicating that a lower dose might be sufficient to reduce severity of disease, but for prevention of transmission other measures would be needed. Frontiers Media S.A. 2021-12-16 /pmc/articles/PMC8716435/ /pubmed/34975888 http://dx.doi.org/10.3389/fimmu.2021.790918 Text en Copyright © 2021 Paudyal, McNee, Rijal, Carr, Nunez, McCauley, Daniels, Townsend, Hammond and Tchilian https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Paudyal, Basudev
McNee, Adam
Rijal, Pramila
Carr, B. Veronica
Nunez, Alejandro
McCauley, John
Daniels, Rodney S.
Townsend, Alain R.
Hammond, John A.
Tchilian, Elma
Low Dose Pig Anti-Influenza Virus Monoclonal Antibodies Reduce Lung Pathology but Do Not Prevent Virus Shedding
title Low Dose Pig Anti-Influenza Virus Monoclonal Antibodies Reduce Lung Pathology but Do Not Prevent Virus Shedding
title_full Low Dose Pig Anti-Influenza Virus Monoclonal Antibodies Reduce Lung Pathology but Do Not Prevent Virus Shedding
title_fullStr Low Dose Pig Anti-Influenza Virus Monoclonal Antibodies Reduce Lung Pathology but Do Not Prevent Virus Shedding
title_full_unstemmed Low Dose Pig Anti-Influenza Virus Monoclonal Antibodies Reduce Lung Pathology but Do Not Prevent Virus Shedding
title_short Low Dose Pig Anti-Influenza Virus Monoclonal Antibodies Reduce Lung Pathology but Do Not Prevent Virus Shedding
title_sort low dose pig anti-influenza virus monoclonal antibodies reduce lung pathology but do not prevent virus shedding
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716435/
https://www.ncbi.nlm.nih.gov/pubmed/34975888
http://dx.doi.org/10.3389/fimmu.2021.790918
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