A Listeria monocytogenes-Based Vaccine That Secretes Sand Fly Salivary Protein LJM11 Confers Long-Term Protection against Vector-Transmitted Leishmania major
A Listeria monocytogenes-Based Vaccine That Secretes Sand Fly Salivary Protein LJM11 Confers Long-Term Protection against Vector-Transmitted Leishmania major
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DOI：
10.1128/iai.01633-14
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发表时间：
2014-07-01
影响因子：
3.1
通讯作者：
Marquis, Helene
中科院分区：
文献类型：
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作者：
Abdallah, Delbert S. Abi;Bitar, Alan Pavinski;Marquis, Helene
皮肤利什曼病是一种白蛉传播的疾病，其特征是皮肤溃疡，并伴有明显的疤痕和社会耻辱。在过去的几年里，越来越多的证据表明，对特定白蛉唾液蛋白的免疫力可以显着预防利什曼病。在这项研究中，我们使用单增李斯特菌减毒株作为 LJM11 的疫苗表达系统，LJM11 是一种白蛉唾液蛋白，被认为是一种良好的候选疫苗。我们观察到，当静脉注射疫苗时，小鼠能够最好地免受大型利什曼原虫和白蛉唾液的皮内针攻击。然而，这种保护是短暂的。重要的是，当受到感染的白蛉攻击时，接种疫苗的小鼠群体得到了长期保护。与接种不表达 LJM11 的单核细胞增生李斯特菌亲本菌株的对照组小鼠相比，攻击后 2 至 6 周期间，保护作用与更小的病变尺寸、更少的疤痕和更好的寄生虫控制相关。此外，攻击后 2 周，保护作用与大量 CD4(+)、γ 干扰素阳性 (IFN-gamma(+))、肿瘤坏死因子 α 阳性/阴性 (TNF-α(+/-))、白细胞介素 10 阴性 (IL-10(-)) 细胞和低数量 CD4(+) IFN γ(+/-) TNF-α(-) IL-10(+) T 细胞相关。总体而言，我们的数据表明，通过李斯特菌传递 LJM11 是一种很有前途的皮肤利什曼病疫苗接种策略，可在受感染的白蛉自然攻击后诱导长期预防溃疡形成。
Cutaneous leishmaniasis is a sand fly-transmitted disease characterized by skin ulcers that carry significant scarring and social stigmatization. Over the past years, there has been cumulative evidence that immunity to specific sand fly salivary proteins confers a significant level of protection against leishmaniasis. In this study, we used an attenuated strain of Listeria monocytogenes as a vaccine expression system for LJM11, a sand fly salivary protein identified as a good vaccine candidate. We observed that mice were best protected against an intradermal needle challenge with Leishmania major and sand fly saliva when vaccinated intravenously. However, this protection was short-lived. Importantly, groups of vaccinated mice were protected long term when challenged with infected sand flies. Protection correlated with smaller lesion size, fewer scars, and better parasite control between 2 and 6 weeks postchallenge compared to the control group of mice vaccinated with the parent L. monocytogenes strain not expressing LJM11. Moreover, protection correlated with high numbers of CD4(+), gamma interferon-positive (IFN-gamma(+)), tumor necrosis factor alpha-positive/negative (TNF-alpha(+/-)), interleukin-10-negative (IL-10(-)) cells and low numbers of CD4(+) IFN gamma(+/-) TNF-alpha(-) IL-10(+) T cells at 2 weeks postchallenge. Overall, our data indicate that delivery of LJM11 by Listeria is a promising vaccination strategy against cutaneous leishmaniasis inducing long-term protection against ulcer formation following a natural challenge with infected sand flies.