Kanekiyo Masaru, Gillespie Rebecca A, Cooper Kristine, Canedo Vanessa Guerra, Castanha Priscila M S, Pegu Amarendra, Yang Eun Sung, Treaster Luke, Yun Gabin, Wallace Megan, Kettenburg Gwenddolen, Williams Connor, Lundy Jeneveve, Barrick Stacey, O'Malley Katherine, Midgett Morgan, Martí Michelle M, Chavva Hasitha, Corry Jacqueline, Treat Benjamin R, Lipinski Abby, Batsche Lucia Ortiz, Creanga Adrian, Ritter Isabella, Walker Reagan, Olsen Emily, Laughlin Amanda, Perez Daniel R, Mascola John R, Boritz Eli A, Loo Yueh-Ming, Blair Wade, Esser Mark, Graham Barney S, Reed Douglas S, Barratt-Boyes Simon M
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Biostatistics Facility, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Science. 2025 Jan 31;387(6733):534-541. doi: 10.1126/science.ado6481. Epub 2025 Jan 30.
Influenza virus pandemics and seasonal epidemics have claimed countless lives. Recurrent zoonotic spillovers of influenza viruses with pandemic potential underscore the need for effective countermeasures. In this study, we show that pre-exposure prophylaxis with broadly neutralizing antibody (bnAb) MEDI8852 is highly effective in protecting cynomolgus macaques from severe disease caused by aerosolized highly pathogenic avian influenza H5N1 virus infection. Protection was antibody dose-dependent yet independent of Fc-mediated effector functions at the dose tested. Macaques receiving MEDI8852 at 10 milligrams per kilogram or higher had negligible impairment of respiratory function after infection, whereas control animals were not protected from severe disease and fatality. Given the breadth of MEDI8852 and other bnAbs, we anticipate that protection from unforeseen pandemic influenza A viruses is achievable.
甲型流感病毒大流行和季节性流行已夺走无数生命。具有大流行潜力的流感病毒反复出现人畜共患传播，凸显了采取有效应对措施的必要性。在本研究中，我们表明，用广谱中和抗体（bnAb）MEDI8852进行暴露前预防，能非常有效地保护食蟹猴免受雾化高致病性禽流感H5N1病毒感染所致的严重疾病。在所测试的剂量下，保护作用呈抗体剂量依赖性，但与Fc介导的效应功能无关。接受每千克10毫克或更高剂量MEDI8852的猕猴在感染后呼吸功能受损可忽略不计，而对照动物未得到严重疾病和死亡的保护。鉴于MEDI8852和其他bnAb的广谱性，我们预计可以实现对不可预见的甲型流感大流行病毒的保护。
