Respiratory syncytial virus (RSV) causes acute lower respiratory tract infections, with potential lower respiratory tract infections, which can be particularly problematic in infants and the elderly. There are no approved vaccines for RSV. The current standard of care for high-risk individuals is monthly administration of palivizumab, a humanized murine monoclonal antibody (mAb) targeting the RSV fusion protein. Adeno-associated virus (AAV)-mediated expression of mAbs has previously led to sustained expression of therapeutic concentrations of mAbs in several animal models, representing an alternative to repetitive passive administration. Intramuscular (IM) administration of AAV6.2FF expressing RSV antibodies, palivizumab or hRSV90, resulted in high concentrations of human (h)IgG1 mAbs in the serum and at various mucosal surfaces, while intranasal administration limited hIgG expression to the respiratory tract. IM administration of AAV6.2FF-hRSV90 or AAV6.2FF-palivizumab in a murine model provided sterilizing immunity against challenge with RSV A2. Evidence of maternal passive transfer of vectorized hRSV90 was detected in both murine and ovine models, with circulating mAbs providing sterilizing immunity in mouse progeny. Finally, addition of a “kill switch” comprised of LoxP sites flanking the mAb genes resulted in diminished serum hIgG after AAV-DJ-mediated delivery of Cre recombinase to the same muscle group that was originally transduced with the AAV-mAb vector. The ability of this AAV-mAb system to mediate robust, sustained mAb expression for maternal transfer to progeny in murine and ovine models emphasizes the potential of this platform for use as an alternative prophylactic vaccine for protection against neonatal infections, particularly in high-risk infants.

呼吸道合胞病毒 (RSV) 引起急性下呼吸道感染，并可能引起下呼吸道感染，这在婴儿和老年人中尤其成问题。没有批准的 RSV 疫苗。目前对高危人群的护理标准是每月服用帕利珠单抗，这是一种针对 RSV 融合蛋白的人源化鼠单克隆抗体 (mAb)。腺相关病毒 (AAV) 介导的 mAb 表达先前已导致在几种动物模型中持续表达治疗浓度的 mAb，代表了重复被动给药的替代方案。肌内 (IM) 施用表达 AAV6.2FF 的 RSV 抗体、帕利珠单抗或 hRSV90，导致血清和各种粘膜表面出现高浓度的人 (h)IgG1 mAb，而鼻内给药限制了 hIgG 在呼吸道的表达。在小鼠模型中肌注 AAV6.2FF-hRSV90 或 AAV6.2FF-palivizumab 提供了针对 RSV A2 攻击的灭菌免疫。在小鼠和绵羊模型中均检测到矢量化 hRSV90 母体被动转移的证据，循环的 mAb 为小鼠后代提供了灭菌免疫。最后，在 AAV-DJ 介导的 Cre 重组酶递送至最初用 AAV-mAb 载体转导的相同肌肉群后，添加由位于 mAb 基因侧翼的 LoxP 位点组成的“杀伤开关”导致血清 hIgG 减少。这种 AAV-mAb 系统介导稳健、