Influenza A viruses pose a significant threat globally each year, underscoring the need for a vaccine- or antiviral-based broad-protection strategy. Here, we describe a chimeric monoclonal antibody, C12H5, that offers neutralization against seasonal and pandemic H1N1 viruses, and cross-protection against some H5N1 viruses. Notably, C12H5 mAb offers broad neutralizing activity against H1N1 and H5N1 viruses by controlling virus entry and egress, and offers protection against H1N1 and H5N1 viral challenge in vivo. Through structural analyses, we show that C12H5 engages hemagglutinin (HA), the major surface glycoprotein on influenza, at a distinct epitope overlapping the receptor binding site and covering the 140-loop. We identified eight highly conserved (~90%) residues that are essential for broad H1N1 recognition, with evidence of tolerance for Asp or Glu at position 190; this site is a molecular determinant for human or avian host-specific recognition and this tolerance endows C12H5 with cross-neutralization potential. Our results could benefit the development of antiviral drugs and the design of broad-protection influenza vaccines.

甲型流感病毒每年都在全球范围内构成重大威胁，强调需要基于疫苗或抗病毒药物的广泛保护策略。在这里，我们描述了一种嵌合单克隆抗体 C12H5，它提供对季节性和大流行 H1N1 病毒的中和作用，以及对一些 H5N1 病毒的交叉保护。值得注意的是，C12H5 mAb 通过控制病毒进出提供广泛的针对 H1N1 和 H5N1 病毒的中和活性，并在体内提供针对 H1N1 和 H5N1 病毒攻击的保护。通过结构分析，我们表明 C12H5 在与受体结合位点重叠并覆盖 140 环的独特表位处与流感病毒的主要表面糖蛋白血凝素 (HA) 结合。我们确定了 8 个高度保守（~90%）的残基，这些残基对于广泛的 H1N1 识别至关重要，在 190 位有对 Asp 或 Glu 耐受的证据；该位点是人类或鸟类宿主特异性识别的分子决定因素，这种耐受性赋予 C12H5 交叉中和潜力。我们的结果可能有利于抗病毒药物的开发和广泛保护流感疫苗的设计。