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Refined semi-lethal aerosol H5N1 influenza model in cynomolgus macaques for evaluation of medical countermeasures

Highly pathogenic avian influenza A H5N1 viruses cause high mortality in humans and have pandemic potential. Effective vaccines and treatments against this threat are urgently needed. Here, we have refined our previously established model of lethal H5N1 infection in cynomolgus macaques. An inhaled a...

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Autores principales: Kanekiyo, Masaru, Gillespie, Rebecca A., Midgett, Morgan, O’Malley, Katherine J., Williams, Connor, Moin, Syed M., Wallace, Megan, Treaster, Luke, Cooper, Kristine, Syeda, Hubza, Kettenburg, Gwenddolen, Rannulu, Hasala, Schmer, Tabitha, Ortiz, Lucia, Da Silva Castanha, Priscila, Corry, Jacqueline, Xia, Mengying, Olsen, Emily, Perez, Daniel, Yun, Gabin, Graham, Barney S., Barratt-Boyes, Simon M., Reed, Douglas S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520834/
https://www.ncbi.nlm.nih.gov/pubmed/37766976
http://dx.doi.org/10.1016/j.isci.2023.107830
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author Kanekiyo, Masaru
Gillespie, Rebecca A.
Midgett, Morgan
O’Malley, Katherine J.
Williams, Connor
Moin, Syed M.
Wallace, Megan
Treaster, Luke
Cooper, Kristine
Syeda, Hubza
Kettenburg, Gwenddolen
Rannulu, Hasala
Schmer, Tabitha
Ortiz, Lucia
Da Silva Castanha, Priscila
Corry, Jacqueline
Xia, Mengying
Olsen, Emily
Perez, Daniel
Yun, Gabin
Graham, Barney S.
Barratt-Boyes, Simon M.
Reed, Douglas S.
author_facet Kanekiyo, Masaru
Gillespie, Rebecca A.
Midgett, Morgan
O’Malley, Katherine J.
Williams, Connor
Moin, Syed M.
Wallace, Megan
Treaster, Luke
Cooper, Kristine
Syeda, Hubza
Kettenburg, Gwenddolen
Rannulu, Hasala
Schmer, Tabitha
Ortiz, Lucia
Da Silva Castanha, Priscila
Corry, Jacqueline
Xia, Mengying
Olsen, Emily
Perez, Daniel
Yun, Gabin
Graham, Barney S.
Barratt-Boyes, Simon M.
Reed, Douglas S.
author_sort Kanekiyo, Masaru
collection PubMed
description Highly pathogenic avian influenza A H5N1 viruses cause high mortality in humans and have pandemic potential. Effective vaccines and treatments against this threat are urgently needed. Here, we have refined our previously established model of lethal H5N1 infection in cynomolgus macaques. An inhaled aerosol virus dose of 5.1 log(10) plaque-forming unit (pfu) induced a strong febrile response and acute respiratory disease, with four out of six macaques succumbing after challenge. Vaccination with three doses of adjuvanted seasonal quadrivalent influenza vaccine elicited low but detectable neutralizing antibody to H5N1. All six vaccinated macaques survived four times the 50% lethal dose of aerosolized H5N1, while four of six unvaccinated controls succumbed to disease. Although vaccination did not protect against severe influenza, vaccinees had reduced respiratory dysfunction and lower viral load in airways compared to controls. We anticipate that our macaque model will play a vital role in evaluating vaccines and antivirals against influenza pandemics.
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spelling pubmed-105208342023-09-27 Refined semi-lethal aerosol H5N1 influenza model in cynomolgus macaques for evaluation of medical countermeasures Kanekiyo, Masaru Gillespie, Rebecca A. Midgett, Morgan O’Malley, Katherine J. Williams, Connor Moin, Syed M. Wallace, Megan Treaster, Luke Cooper, Kristine Syeda, Hubza Kettenburg, Gwenddolen Rannulu, Hasala Schmer, Tabitha Ortiz, Lucia Da Silva Castanha, Priscila Corry, Jacqueline Xia, Mengying Olsen, Emily Perez, Daniel Yun, Gabin Graham, Barney S. Barratt-Boyes, Simon M. Reed, Douglas S. iScience Article Highly pathogenic avian influenza A H5N1 viruses cause high mortality in humans and have pandemic potential. Effective vaccines and treatments against this threat are urgently needed. Here, we have refined our previously established model of lethal H5N1 infection in cynomolgus macaques. An inhaled aerosol virus dose of 5.1 log(10) plaque-forming unit (pfu) induced a strong febrile response and acute respiratory disease, with four out of six macaques succumbing after challenge. Vaccination with three doses of adjuvanted seasonal quadrivalent influenza vaccine elicited low but detectable neutralizing antibody to H5N1. All six vaccinated macaques survived four times the 50% lethal dose of aerosolized H5N1, while four of six unvaccinated controls succumbed to disease. Although vaccination did not protect against severe influenza, vaccinees had reduced respiratory dysfunction and lower viral load in airways compared to controls. We anticipate that our macaque model will play a vital role in evaluating vaccines and antivirals against influenza pandemics. Elsevier 2023-09-06 /pmc/articles/PMC10520834/ /pubmed/37766976 http://dx.doi.org/10.1016/j.isci.2023.107830 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Kanekiyo, Masaru
Gillespie, Rebecca A.
Midgett, Morgan
O’Malley, Katherine J.
Williams, Connor
Moin, Syed M.
Wallace, Megan
Treaster, Luke
Cooper, Kristine
Syeda, Hubza
Kettenburg, Gwenddolen
Rannulu, Hasala
Schmer, Tabitha
Ortiz, Lucia
Da Silva Castanha, Priscila
Corry, Jacqueline
Xia, Mengying
Olsen, Emily
Perez, Daniel
Yun, Gabin
Graham, Barney S.
Barratt-Boyes, Simon M.
Reed, Douglas S.
Refined semi-lethal aerosol H5N1 influenza model in cynomolgus macaques for evaluation of medical countermeasures
title Refined semi-lethal aerosol H5N1 influenza model in cynomolgus macaques for evaluation of medical countermeasures
title_full Refined semi-lethal aerosol H5N1 influenza model in cynomolgus macaques for evaluation of medical countermeasures
title_fullStr Refined semi-lethal aerosol H5N1 influenza model in cynomolgus macaques for evaluation of medical countermeasures
title_full_unstemmed Refined semi-lethal aerosol H5N1 influenza model in cynomolgus macaques for evaluation of medical countermeasures
title_short Refined semi-lethal aerosol H5N1 influenza model in cynomolgus macaques for evaluation of medical countermeasures
title_sort refined semi-lethal aerosol h5n1 influenza model in cynomolgus macaques for evaluation of medical countermeasures
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520834/
https://www.ncbi.nlm.nih.gov/pubmed/37766976
http://dx.doi.org/10.1016/j.isci.2023.107830
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