ContraFect Corporation, Yonkers, New York, USA.
Trellis Bioscience, Menlo Park, California, USA.
Antimicrob Agents Chemother. 2018 Apr 26;62(5). doi: 10.1128/AAC.02269-17. Print 2018 May.
Although antibodies that effectively neutralize a broad set of influenza viruses exist in the human antibody repertoire, they are rare. We used a single-cell screening technology to identify rare monoclonal antibodies (MAbs) that recognized a broad set of influenza B viruses (IBV). The screen yielded 23 MAbs with diverse germ line origins that recognized hemagglutinins (HAs) derived from influenza strains of both the Yamagata and Victoria lineages of IBV. Of the 23 MAbs, 3 exhibited low expression in a transient-transfection system, 4 were neutralizers that bound to the HA head region, 11 were stalk-binding nonneutralizers, and 5 were stalk-binding neutralizers, with 4 of these 5 having unique antibody sequences. Of these four unique stalk-binding neutralizing MAbs, all were broadly reactive and neutralizing against a panel of multiple strains spanning both IBV lineages as well as highly effective in treating lethal IBV infections in mice at both 24 and 72 h postinfection. The MAbs in this group were thermostable and bound different epitopes in the highly conserved HA stalk region. These characteristics suggest that these MAbs are suitable for consideration as candidates for clinical studies to address their effectiveness in the treatment of IBV-infected patients.
虽然人类抗体库中存在能够有效中和广泛流感病毒的抗体，但这些抗体非常罕见。我们使用单细胞筛选技术来鉴定能够识别广泛乙型流感病毒（IBV）的稀有单克隆抗体（Mab）。该筛选产生了 23 种具有不同种系起源的 Mab，它们识别来自 IBV 的 Yamagata 和 Victoria 谱系的流感株的血凝素（HA）。在瞬时转染系统中，这 23 种 Mab 中有 3 种表达水平较低，4 种是中和抗体，能结合 HA 头部区域，11 种是茎结合非中和抗体，5 种是茎结合中和抗体，其中 5 种具有独特的抗体序列。在这 4 种独特的茎结合中和 Mab 中，所有 Mab 都对跨越两种 IBV 谱系的多种株系具有广泛的反应性和中和活性，并且在感染后 24 和 72 小时对感染致死性 IBV 的小鼠具有非常有效的治疗作用。该组 Mab 具有热稳定性，并且结合 HA 茎高度保守区域中的不同表位。这些特征表明，这些 Mab 适合作为临床研究的候选物，以评估它们在治疗 IBV 感染患者中的有效性。
