Maternal immunization with chimpanzee adenovirus expressing RSV fusion protein protects against neonatal RSV pulmonary infection.
Maternal immunization with chimpanzee adenovirus expressing RSV fusion protein protects against neonatal RSV pulmonary infection.
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母体免疫接种表达 RSV 融合蛋白的黑猩猩腺病毒可预防新生儿 RSV 肺部感染。
DOI：
10.1016/j.vaccine.2014.08.049
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发表时间：
2014
期刊：
影响因子：
5.5
通讯作者：
Worgall,Stefan
中科院分区：
文献类型：
--
作者：
Sharma,Anurag;Wendland,Rebecca;Sung,Biin;Wu,Wenzhu;Grunwald,Thomas;Worgall,Stefan
呼吸道合胞病毒（RSV）是婴幼儿下呼吸道疾病的主要病因，发病率和死亡率高。尽管做出了许多努力，但针对RSV的许可疫苗仍然难以捉摸。由于婴幼儿是RSV疾病的主要目标群体，因此母亲免疫以增强新生儿的保护是一种有吸引力的策略。在这项研究中，我们测试了用表达密码子优化的RSV融合蛋白（AdC 7-Fsyn）的黑猩猩腺病毒免疫母亲以保护婴儿免受RSV感染的功效。通过AdC 7-Fsyn对小鼠进行单次鼻内免疫诱导了稳健的抗RSV全身和粘膜免疫，其保护免受RSV而不引起疫苗增强的RSV疾病。将RSV体液免疫转移到免疫母亲所生的幼仔中，这些幼仔提供针对RSV的保护。用AdC 7-Fsyn免疫是有效的，即使在存在Ad 5预免疫的情况下。母源性免疫力持久，半衰期为14.63天，可将病毒复制减少至15周龄。值得注意的是，被动免疫的小鼠可以用AdC 7-Fsyn主动再免疫以加强和延长保护。这证实了用表达RSV F的基于AdC 7的疫苗进行母体免疫是在生命早期保护免受RSV的可行方法。
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease with high morbidity and mortality in young infants and children. Despite numerous efforts, a licensed vaccine against RSV remains elusive. Since young infants form the primary target group of RSV disease, maternal immunization to boost the protection in neonates is an attractive strategy. In this study we tested the efficacy of maternal immunization with a chimpanzee adenovirus expressing codon-optimized RSV fusion protein (AdC7-Fsyn) to protect infants against RSV infection. Single intranasal immunization of mice by AdC7-Fsyn induced robust anti-RSV systemic and mucosal immunity that protected against RSV without causing vaccine-enhanced RSV disease. RSV humoral immunity was transferred to pups born to immunized mothers that provided protection against RSV. Immunization with AdC7-Fsyn was effective even in the presence of Ad5 preimmunity. The maternally derived immunity was durable with the half-life of 14.63 days that reduced the viral replication up to 15 weeks of age. Notably, the passively immunized mice could be actively re-immunized with AdC7-Fsyn to boost and extend the protection. This substantiates maternal immunization with an AdC7-based vaccine expressing RSV F as feasible approach to protect against RSV early in life.