您現在的位置:首頁> 外文學位 >文獻詳情

The Characterization of Novel Transgenic Murine Models of Neisseria gonorrhoeae Infection and Development of a Natural Outer Membrane Vesicle Anti-Gonococcal Vaccine Candidate

機器翻譯新型轉基因小鼠淋病奈瑟菌感染模型的表征及天然外膜囊泡抗淋球菌疫苗候選物的研制

原文傳遞 加入購物車 收藏
30 【6hr】

【摘要】Untreatable gonorrhea, caused by fully antimicrobial resistant Neisseria gonorrhoeae (GC), is a major global health threat. While a vaccine would greatly help address this crisis, development of a GC vaccine is complicated by the lack of lab models of symptomatic gonorrhea. We hypothesized that overt disease in animal models of gonorrhea is limited by the human-restriction of gonococcal virulence factors, and the impact of the reproductive hormone cycle (estrus and diestrus phases). We tested these hypotheses by examining the host response to infection in transgenic mice expressing targets of bacterial adhesion, human carcinoembryonic antigen-related cell adhesion molecules (hCEACAMs), in uterine versus vaginal infections, and in different phases of the reproductive cycle (estrus and diestrus phases). hCEACAM expression most impacted estrus phase infections, prolonging colonization in vaginal infection and inducing greater inflammation in uterine. Reproductive phase greatly influenced host response to uterine infection as diestrus infection was more inflammatory than estrus. Phase differences in uterine infection were driven by greater activation of a chemokine-centric common anti gonococcal response and unique induction of type 1 interferons in diestrus. These findings suggest that symptomatic uterine and vaginal GC infection can be modeled by transcervically infected wild-type diestrus mice and transgenic, vaginally-infected estrus mice, respectively.;A novel approach to GC vaccine development is also needed. Mono-antigenic vaccines have failed to produce immunity suggesting a poly-antigenic antigen, like natural outer membrane vesicles (nOMVs) may be necessary. It has been shown that any GC vaccine must lack the bacterioprotective antigen, reduction modifiable protein (RMP), and no such nOMV has been previously described. Here we report successful isolation of RMP-deficient nOMVs through sequential size and weight restrictive filtration. Vesicle morphology, proteomics, and bioactivity was characterized via various methods. nOMVs were found to be consistent in size, shape and antigenic load. As antigens, nOMVs induced high serum titers and measurable vaginal levels of antigen and GC specific IgG that recognized several nOMV immunogens supporting the vaccine potential of GC nOMVs. These findings lay the groundwork for protective studies of nOMV vaccines in novel models of active gonorrhea moving the field closer to discovering the mechanism of protective anti-gonococcal immunity.

【作者】Francis, Ian P.;

【作者單位】Boston University.;

【年(卷),期】2020,,

【頁碼】202 p.

【總頁數】202

【正文語種】

【中圖分類】;

【關鍵詞】;


激情球迷怎么玩 安徽25选5中奖规则 河内五分彩杀号方法 3d计划毒王 森林舞会压分必赢方法 舟山体彩飞鱼下载 澳洲幸运5平台 山东时时彩走势图 nba让分胜负爆料 重庆时时彩杀一位 360彩票网官网下载 足彩半全场胜负 陕西快乐10分软件 单机开心农场游戏中文 1000炮金蟾捕鱼棋牌 广东省福利彩票软件 孙悟空初期赚钱方法