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
Molecular Engineering Section, Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA.
Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.
iScience. 2023 Sep 6;26(10):107830. doi: 10.1016/j.isci.2023.107830. eCollection 2023 Oct 20.
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 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.
高致病性甲型H5N1禽流感病毒可导致人类高死亡率，并具有大流行潜力。迫切需要针对这一威胁的有效疫苗和治疗方法。在此，我们改进了之前建立的食蟹猴致死性H5N1感染模型。吸入5.1对数蚀斑形成单位（pfu）的气溶胶病毒剂量可引发强烈的发热反应和急性呼吸道疾病，6只猕猴中有4只在感染后死亡。接种三剂佐剂季节性四价流感疫苗可诱导产生低水平但可检测到的针对H5N1的中和抗体。所有6只接种疫苗的猕猴在接受4倍50%致死剂量的雾化H5N1攻击后存活，而6只未接种疫苗的对照中有4只死于疾病。虽然接种疫苗不能预防严重流感，但与对照组相比，接种疫苗的猕猴呼吸功能障碍减轻，气道中的病毒载量更低。我们预计，我们的猕猴模型将在评估针对流感大流行的疫苗和抗病毒药物方面发挥至关重要的作用。
