Gomi Rika, Sharma Anurag, Wu Wenzhu, Worgall Stefan
Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA.
Department of Genetic Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Vaccines (Basel). 2018 Dec 29;7(1):3. doi: 10.3390/vaccines7010003.
Respiratory syncytial virus (RSV) is one of the leading causes of lower respiratory tract infection in infants. Immunoprophylaxis with the anti-RSV monoclonal antibody, palivizumab, reduces the risk for RSV-related hospitalizations, but its use is restricted to high-risk infants due to the high costs. In this study, we investigated if genetic delivery of anti-RSV antibody to neonatal mice by chimpanzee adenovirus type 7 expressing the murine form of palivizumab (AdC7αRSV) can provide protection against RSV. Intranasal and intramuscular administration of AdC7αRSV to adult mice resulted in similar levels of anti-RSV IgG in the serum. However, only intranasal administration resulted in detectable levels of anti-RSV IgG in the bronchoalveolar lavage fluid. Intranasal administration of AdC7αRSV provided protection against subsequent RSV challenge. Expression of the anti-RSV antibody was prolonged following intranasal administration of AdC7αRSV to neonatal mice. Protection against RSV was confirmed at 6 weeks of age. These data suggest that neonatal genetic delivery of anti-RSV antibody by AdC7αRSV can provide protection against RSV.
呼吸道合胞病毒(RSV)是婴儿下呼吸道感染的主要病因之一。使用抗RSV单克隆抗体帕利珠单抗进行免疫预防可降低RSV相关住院风险,但由于成本高昂,其使用仅限于高危婴儿。在本研究中,我们调查了通过表达鼠源形式帕利珠单抗的黑猩猩7型腺病毒(AdC7αRSV)将抗RSV抗体基因传递给新生小鼠是否能提供针对RSV的保护。对成年小鼠进行鼻内和肌肉注射AdC7αRSV后,血清中抗RSV IgG水平相似。然而,只有鼻内给药导致支气管肺泡灌洗液中可检测到抗RSV IgG水平。鼻内给药AdC7αRSV可提供针对后续RSV攻击的保护。对新生小鼠鼻内给药AdC7αRSV后,抗RSV抗体的表达持续时间延长。在6周龄时证实了对RSV的保护作用。这些数据表明,通过AdC7αRSV对新生小鼠进行抗RSV抗体的基因传递可提供针对RSV的保护。