Protective MCMV immunity by vaccination of the salivary gland via Wharton's duct: replication-deficient recombinant adenovirus expressing individual MCMV genes elicits protection similar to that of MCMV.
Protective MCMV immunity by vaccination of the salivary gland via Wharton's duct: replication-deficient recombinant adenovirus expressing individual MCMV genes elicits protection similar to that of MCMV.
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通过沃顿氏管接种唾液腺来产生保护性 MCMV 免疫：表达单个 MCMV 基因的复制缺陷型重组腺病毒可引起与 MCMV 类似的保护。
DOI：
10.1096/fj.13-244178
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
London,StevenD
中科院分区：
文献类型：
--
作者：
Liu,Guangliang;Zhang,Fangfang;Wang,Ruixue;London,Lucille;London,StevenD
唾液腺是粘膜免疫系统的主要组成部分，对粘膜获得性病原体具有抗原特异性免疫。我们研究了生理接种途径和亚单位疫苗方法是否能引起mcmv特异性和保护性免疫。通过华顿氏管逆行灌注小鼠下颌下唾液腺，通过表达MCMV基因的复制缺陷腺病毒（gB、gH、IE1；对照组：生理盐水和不含MCMV插入物的复制缺陷腺病毒）将tcMCMV或MCMV蛋白聚焦到唾液腺。小鼠被评估MCMV特异性抗体、t细胞反应、生发中心形成和对致命MCMV攻击的保护。逆行灌注tcMCMV或腺病毒表达的MCMV蛋白诱导全身和粘膜MCMV特异性抗体增加2- 6倍，GC标记物表达增加3- 6倍，并对致命的全身攻击具有保护作用，其证据是高达80%的生存率增加，脾脏病理减少，病毒滴度从106 pfu降至不可检测的水平。因此，涎腺免疫通过蛋白抗原诱导全身和粘膜保护性免疫反应的生理途径。因此，唾液腺免疫可以作为接种疫苗的另一种粘膜途径，直接适用于人类。-Liu， G., Zhang， F., Wang， R., London， L., London， S. D.通过Wharton氏管接种唾液腺疫苗对MCMV进行保护性免疫：表达MCMV个体基因的复制缺陷重组腺病毒可获得与MCMV相似的保护作用。
Salivary glands, a major component of the mucosal immune system, confer antigen-specific immunity to mucosally acquired pathogens. We investigated whether a physiological route of inoculation and a subunit vaccine approach elicited MCMV-specific and protective immunity. Mice were inoculated by retrograde perfusion of the submandibular salivary glands via Wharton's duct with tcMCMV or MCMV proteins focused to the salivary gland via replication-deficient adenovirus expressing individual MCMV genes (gB, gH, IE1; controls: saline and replication deficient adenovirus without MCMV inserts). Mice were evaluated for MCMV-specific antibodies, T-cell responses, germinal center formation, and protection against a lethal MCMV challenge. Retrograde perfusion with tcMCMV or adenovirus expressed MCMV proteins induced a 2- to 6-fold increase in systemic and mucosal MCMV-specific antibodies, a 3- to 6-fold increase in GC marker expression, and protection against a lethal systemic challenge, as evidenced by up to 80% increased survival, decreased splenic pathology, and decreased viral titers from 106 pfu to undetectable levels. Thus, a focused salivary gland immunization via a physiological route with a protein antigen induced systemic and mucosal protective immune responses. Therefore, salivary gland immunization can serve as an alternative mucosal route for administering vaccines, which is directly applicable for use in humans.—Liu, G., Zhang, F., Wang, R., London, L., London, S. D. Protective MCMV immunity by vaccination of the salivary gland via Wharton's duct: replication-deficient recombinant adenovirus expressing individual MCMV genes elicits protection similar to that of MCMV.