Infants and older adults are especially vulnerable to infection by respiratory syncytial virus (RSV), which can cause significant illness and irreparable damage to the lower respiratory tract and for which an effective vaccine is not readily available. Palivizumab, a recombinant monoclonal antibody (mAb), is an approved therapeutic for RSV infection for use in high-risk infants only. Due to several logistical issues, including cost of goods and scale-up limitations, palivizumab is not approved for other populations that are vulnerable to severe RSV infections, such as older adults. In this study, we demonstrate that intranasal delivery of adeno-associated virus serotype 9 (AAV9) vector expressing palivizumab or motavizumab, a second-generation version of palivizumab, significantly reduced the viral load in the lungs of the BALB/c mouse model of RSV infection. Notably, we demonstrate that AAV9 vector-mediated prophylaxis against RSV was effective despite the presence of serum-circulating neutralizing AAV9 antibodies. These findings substantiate the feasibility of repeatedly administering AAV9 vector to the airway for seasonal prophylaxis against RSV, thereby expanding the application of vectored delivery of mAbs as an effective prophylaxis strategy against various airborne viruses.

中文翻译：

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腺相关病毒载体介导的抗呼吸道合胞病毒抗体表达可预防小鼠气道感染

婴儿和老年人特别容易受到呼吸道合胞病毒 (RSV) 的感染，这会导致严重的疾病和对下呼吸道造成无法弥补的损害，而且目前还没有有效的疫苗。Palivizumab 是一种重组单克隆抗体 (mAb)，是一种经批准的 RSV 感染治疗剂，仅用于高危婴儿。由于若干后勤问题，包括商品成本和扩大规模限制，帕利珠单抗未被批准用于其他易受严重 RSV 感染的人群，如老年人。在这项研究中，我们证明了表达帕利珠单抗或莫他珠单抗（帕利珠单抗的第二代版本）的腺相关病毒血清型 9 (AAV9) 载体的鼻内递送，显着降低了 RSV 感染的 BALB/c 小鼠模型肺部的病毒载量。值得注意的是，我们证明尽管存在血清循环中和 AAV9 抗体，但 AAV9 载体介导的针对 RSV 的预防是有效的。这些发现证实了反复向气道施用 AAV9 载体以对 RSV 进行季节性预防的可行性，从而扩大了 mAb 载体递送作为针对各种空气传播病毒的有效预防策略的应用。