Division of Biology, California Institute of Technology, Pasadena, California, USA.
Nat Biotechnol. 2013 Jul;31(7):647-52. doi: 10.1038/nbt.2618. Epub 2013 Jun 2.
Neutralizing antibodies that target epitopes conserved among many strains of influenza virus have been recently isolated from humans. Here we demonstrate that adeno-associated viruses (AAV) encoding two such broadly neutralizing antibodies are protective against diverse influenza strains. Serum from mice that received a single intramuscular AAV injection efficiently neutralized all H1, H2 and H5 influenza strains tested. After infection with diverse strains of H1N1 influenza, treated mice showed minimal weight loss and lung inflammation. Protection lasted for at least 11 months after AAV injection. Notably, even immunodeficient and older mice were protected by this method, suggesting that expression of a monoclonal antibody alone is sufficient to protect mice from illness. If translated to humans, this prophylactic approach may be uniquely capable of protecting immunocompromised or elderly patient populations not reliably protected by existing vaccines.
最近从人类中分离出了针对流感病毒许多株系保守表位的中和抗体。在这里，我们证明，编码两种此类广泛中和抗体的腺相关病毒 (AAV) 可预防多种流感株系。接受单次肌肉内 AAV 注射的小鼠的血清可有效中和所有测试的 H1、H2 和 H5 流感株系。感染不同株系的 H1N1 流感后，接受治疗的小鼠体重减轻和肺部炎症最小。在 AAV 注射后至少 11 个月仍能保持保护作用。值得注意的是，即使是免疫功能低下和老年小鼠也能通过这种方法得到保护，这表明单克隆抗体的表达本身就足以保护小鼠免受疾病的侵害。如果将其转化为人类，这种预防性方法可能是唯一能够保护因现有疫苗无法可靠保护而免疫功能低下或老年患者人群的方法。
