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

用于评估医疗对策的食蟹猴改良型半致死性气溶胶H5N1流感模型

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作者:Masaru Kanekiyo ,Rebecca A Gillespie ,Morgan Midgett ,Katherine J O'Malley ,Connor Williams ,Syed M Moin ,Megan Wallace ,Luke Treaster ,Kristine Cooper ,Hubza Syeda ,Gwenddolen Kettenburg ,Hasala Rannulu ,Tabitha Schmer ,Lucia Ortiz ,Priscila Da Silva Castanha ,Jacqueline Corry ,Mengying Xia ,Emily Olsen ,Daniel Perez ,Gabin Yun ,Barney S Graham ,Simon M Barratt-Boyes ,Douglas S Reed

Abstract

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 log10 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. Keywords: Immunology; Model organism; Virology.

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