Department for Molecular Biomedical Research, VIB, Ghent University, Belgium.
J Infect Dis. 2011 Dec 1;204(11):1692-701. doi: 10.1093/infdis/jir622. Epub 2011 Oct 12.
Despite the medical importance of respiratory syncytial virus (RSV) infections, there is no vaccine or therapeutic agent available. Prophylactic administration of palivizumab, a humanized monoclonal RSV fusion (F) protein-specific antibody, can protect high-risk children. Previously, we have demonstrated that RSV can be neutralized by picomolar concentrations of a camelid immunoglobulin single-variable domain that binds the RSV protein F (F-VHHb nanobodies). Here, we investigated the mechanism by which these nanobodies neutralize RSV and tested their antiviral activity in vivo. We demonstrate that bivalent RSV F-specific nanobodies neutralize RSV infection by inhibiting fusion without affecting viral attachment. The ability of RSV F-specific nanobodies to protect against RSV infection was investigated in vivo. Intranasal administration of bivalent RSV F-specific nanobodies protected BALB/c mice from RSV infection, and associated pulmonary inflammation. Moreover, therapeutic treatment with these nanobodies after RSV infection could reduce viral replication and reduced pulmonary inflammation. Thus, nanobodies are promising therapeutic molecules for treatment of RSV.
尽管呼吸道合胞病毒 (RSV) 感染具有重要的医学意义，但目前尚无可用的疫苗或治疗药物。预防性给予帕利珠单抗（一种人源化单克隆 RSV 融合 (F) 蛋白特异性抗体）可以保护高危儿童。此前，我们已经证明 RSV 可以被结合 RSV 蛋白 F 的骆驼免疫球蛋白单可变结构域（F-VHHb 纳米抗体）以皮摩尔浓度中和。在这里，我们研究了这些纳米抗体中和 RSV 的机制，并在体内测试了它们的抗病毒活性。我们证明二价 RSV F 特异性纳米抗体通过抑制融合而不影响病毒附着来中和 RSV 感染。我们在体内研究了 RSV F 特异性纳米抗体预防 RSV 感染的能力。鼻内给予二价 RSV F 特异性纳米抗体可保护 BALB/c 小鼠免受 RSV 感染和相关的肺部炎症。此外，在 RSV 感染后用这些纳米抗体进行治疗可以减少病毒复制并减轻肺部炎症。因此，纳米抗体是治疗 RSV 的有前途的治疗分子。
