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

Autor: Kanekiyo M; Molecular Engineering Section, Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA., Gillespie RA; Molecular Engineering Section, Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA., Midgett M; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA., O'Malley KJ; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA., Williams C; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA., Moin SM; Molecular Engineering Section, Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA., Wallace M; Department of Infectious Disease and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA., Treaster L; Division of Cardiothoracic Imaging, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Cooper K; Biostatistics Facility, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA., Syeda H; Molecular Engineering Section, Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA., Kettenburg G; Department of Infectious Disease and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA., Rannulu H; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA., Schmer T; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA., Ortiz L; Department of Population Health, University of Georgia, Athens, GA, USA., Da Silva Castanha P; Department of Infectious Disease and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA., Corry J; Department of Infectious Disease and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA., Xia M; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA., Olsen E; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA., Perez D; Department of Population Health, University of Georgia, Athens, GA, USA., Yun G; Division of Cardiothoracic Imaging, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Graham BS; Molecular Engineering Section, Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA., Barratt-Boyes SM; Department of Infectious Disease and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA., Reed DS; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.
Jazyk: angličtina
Zdroj: IScience [iScience] 2023 Sep 06; Vol. 26 (10), pp. 107830. Date of Electronic Publication: 2023 Sep 06 (Print Publication: 2023).
DOI: 10.1016/j.isci.2023.107830
Abstrakt: 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.
Competing Interests: The authors declare that they have no competing interests or conflicts.
(© 2023 The Authors.)
Databáze: MEDLINE
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