Paules Catharine I, Lakdawala Seema, McAuliffe Josephine M, Paskel Myeisha, Vogel Leatrice, Kallewaard Nicole L, Zhu Qing, Subbarao Kanta
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda.
Department of Infectious Disease and Vaccines, Medimmune LLC, Gaithersburg, Maryland.
J Infect Dis. 2017 Aug 1;216(3):356-365. doi: 10.1093/infdis/jix292.
MEDI8852 is a novel monoclonal antibody (mAb) that neutralizes both group I and group II influenza A viruses (IAVs) in vitro. We evaluated whether MEDI8852 was effective for prophylaxis and therapy against representative group I (H5N1) and group II (H7N9) pandemic IAVs in mice and ferrets and could be used to block transmission of influenza H1N1pdm09 in ferrets, compared to an irrelevant control mAb R347 and oseltamivir.
MEDI8852 was administered to mice and ferrets by intraperitoneal injection at varying doses, 24 hours prior to intranasal infection with H5N1 and H7N9 viruses for prophylaxis, and 24, 48, and 72 hours post-infection for treatment. A comparison with oseltamivir alone and combination of MEDI8852 and oseltamivir was included in some studies. Survival, weight loss, and viral titers were assessed over a 14-day study period. For the transmission study, naive respiratory contact ferrets received MEDI8852 or R347 prior to exposure to ferrets infected with an H1N1pdm09 virus.
MEDI8852 was effective for prophylaxis and treatment of H7N9 and H5N1 infection in mice, with a clear dose-dependent response and treatment with MEDI8852 24, 48, or 72 hours postinfection was superior to oseltamivir for H5N1. MEDI8852 alone was effective treatment for lethal H5N1 infection in ferrets compared to oseltamivir and R347, and MEDI8852 plus oseltamivir was better than oseltamivir alone. MEDI8852 or oseltamivir alone early in infection was equally effective for H7N9 infection in ferrets while the combination yielded similar protection when treatment was delayed. MEDI8852 was able to protect naive ferrets from airborne transmission of H1N1pdm09.
MEDI8852, alone or with oseltamivir, shows promise for prophylaxis or therapy of group I and II IAVs with pandemic potential. Additionally, MEDI8852 blocked influenza transmission in ferrets, a unique finding among influenza-specific mAbs.
MEDI8852是一种新型单克隆抗体（mAb），在体外可中和甲型流感病毒（IAV）的I组和II组病毒。我们评估了MEDI8852在小鼠和雪貂中对具有代表性的I组（H5N1）和II组（H7N9）大流行性IAV进行预防和治疗的效果，以及与无关对照单克隆抗体R347和奥司他韦相比，其是否可用于阻断雪貂中甲型H1N1pdm09流感病毒的传播。
在经鼻感染H5N1和H7N9病毒前24小时，以不同剂量通过腹腔注射将MEDI8852给予小鼠和雪貂用于预防，在感染后24、48和72小时给予用于治疗。一些研究纳入了单独使用奥司他韦以及MEDI8852与奥司他韦联合使用的比较。在为期14天的研究期间评估存活率、体重减轻和病毒滴度。对于传播研究，未感染的呼吸道接触雪貂在接触感染甲型H1N1pdm09病毒的雪貂之前接受MEDI8852或R347。
MEDI8852对小鼠的H7N9和H5N1感染的预防和治疗有效，具有明显的剂量依赖性反应，且感染后24、48或72小时用MEDI8852治疗对H5N1的效果优于奥司他韦。与奥司他韦和R347相比，单独使用MEDI8852对雪貂的致死性H5N1感染有效，且MEDI8852加奥司他韦比单独使用奥司他韦效果更好。感染早期单独使用MEDI8852或奥司他韦对雪貂的H7N9感染同样有效，而延迟治疗时联合使用产生相似的保护效果。MEDI8852能够保护未感染的雪貂免受甲型H1N1pdm09的空气传播。
MEDI8852单独或与奥司他韦联合使用，在预防或治疗具有大流行潜力的I组和II组IAV方面显示出前景。此外，MEDI8852可阻断雪貂中的流感传播，这在流感特异性单克隆抗体中是一个独特的发现。
