Vaccination inhibits the human adenoviral transduction in a mouse keratoconjunctivits model.
Vaccination inhibits the human adenoviral transduction in a mouse keratoconjunctivits model.
复制标题
疫苗接种可抑制小鼠角结膜模型中的人腺病毒转导。
DOI：
10.1016/j.vaccine.2021.05.010
复制
发表时间：
2021
期刊：
影响因子：
5.5
通讯作者：
Shimada M.
中科院分区：
文献类型：
--
作者：
Fukuda M;Nakamura J;Ito S;Kawazoe K;Miyanaga Y;Teshigawara T;Okuda K;Mizuki N;Shimada M.
腺病毒感染是流行性角膜结膜炎（EKC）的主要原因，可导致角膜上皮下浸润和多灶性角膜混浊。在目前的研究中，我们研究了使用E1/E3缺失的腺病毒血清型5（Ad 5）载体作为疫苗肌肉内（IM）或鼻内（IN）接种，以对抗随后通过滴眼液用表达腺苷三磷酸酶的Ad 5（Ad 5-Luci）载体的攻击。我们评估了对Ad 5载体疫苗接种的适应性免疫应答，并证实了脾细胞中稳健的多功能CD 8 T细胞应答。还测量了接种小鼠血清中的中和Ad 5抗体以及洗眼液中的Ad 5抗体。在初次免疫后8周用Ad 5-Luci载体攻击时，在接种疫苗的小鼠中转导显著减少> 70%，这在IM-接种疫苗的动物中略好于IN-接种疫苗的动物。初次IM接种后10个月观察到对后续攻击的抗性，其中Ad 5-Luci载体转导持续降低高达60%。用来自IM的抗血清被动免疫幼稚小鼠至随后用Ad 5-Luci载体攻击的接种小鼠，导致转导效率损失约40%。此外，在有或没有CD 8 T细胞耗竭的情况下接受IM免疫的小鼠在Ad 8局部攻击后分别显示出Ad 8基因组拷贝减少> 40%和70%。我们的结论是，腺病毒载体疫苗接种成功地诱导了适应性免疫反应，防止随后的腺病毒角膜结膜炎小鼠模型中的角膜和结膜相关组织中的腺病毒转导，细胞和体液免疫在防止腺病毒转导中发挥重要作用。
Adenovirus infections are a major cause of epidemic keratoconjunctivitis (EKC), which can lead to corneal subepithelial infiltrates and multifocal corneal opacity. In the current study, we investigated the use of an E1/E3-deleted adenovirus serotype 5 (Ad5) vector as a vaccine administered intramuscularly (IM) or intranasally (IN) against subsequent challenges with a luciferase-expressing Ad5 (Ad5-Luci) vector via eyedrop. We evaluated the adaptive immune response to Ad5 vector vaccination and confirmed a robust polyfunctional CD8 T cell response in splenic cells. Neutralizing Ad5 antibodies were also measured in the sera of vaccinated mice as well as Ad5 antibody in the eye wash solutions. Upon challenge with Ad5-Luci vector 8 weeks post the primary immunization, transduction was significantly reduced by > 70% in the vaccinated mice, which was slightly better in IM-vs. that in IN-vaccinated animals. Resistance to subsequent challenge was observed 10 months post primary IM vaccination, with sustained reduction up to 60% in the Ad5-Luci vector transduction. Passive immunization of naive mice with antisera from IM to vaccinated mice subsequently challenged with the Ad5-Luci vector resulted in approximately 40% loss in transduction efficiency. Furthermore, the mice that received IM immunization with or without CD8 T cell depletion showed > 40% and 70% reductions, respectively, in Ad8 genomic copies after Ad8 topical challenge. We conclude that Ad-vector vaccination successfully induced an adaptive immune response that prevented subsequent Ad transduction in the cornea and conjunctiva-associated tissues in a mouse model of adenovirus keratoconjunctivitis, and that both cellular and humoral immunity play an important role in preventing Ad transduction.