Mucosal co-immunization of mice with recombinant lactococci secreting VapA antigen and leptin elicits a protective immune response against Rhodococcus equi infection
Mucosal co-immunization of mice with recombinant lactococci secreting VapA antigen and leptin elicits a protective immune response against Rhodococcus equi infection
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DOI：
10.1016/j.vaccine.2011.10.026
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发表时间：
2011-12-09
期刊：
影响因子：
5.5
通讯作者：
Cauchard, J.
中科院分区：
文献类型：
--
作者：
Cauchard, S.;Bermudez-Humaran, L. G.;Cauchard, J.
马红球菌会引起马驹的严重肺炎，并且最近作为免疫功能低下的人类中的重要机会病原体而受到关注。然而，目前还没有有效的疫苗来预防红球菌病。在这项研究中，我们工程化了食品级细菌乳球菌，它能够分泌来自马乳球菌的毒力相关蛋白 A (LL-VapA)。然后，在单独或与 LL-Lep（一种分泌生物活性瘦素（一种具有显着免疫调节特性的多效性激素）的乳酸乳球菌重组菌株）对小鼠进行胃内或鼻内免疫后，评估 LL-VapA 菌株的免疫原性潜力。胃内施用 LL-VapA 导致最高的 VapA 特异性粘膜反应，而鼻内施用导致最高的全身免疫反应。在所有免疫组中，体外刺激的脾细胞释放的细胞因子均表现出强烈的 IFN-γ 反应，并且 IL-4 水平增加，但鼻内同时施用 LL-VapA 和 LL-Lep 的组除外。引人注目的是，在所有免疫组中，除了通过胃内途径接种 LL-VapA 的组之外，在用马罗氏菌强毒株静脉内攻击四天后，观察到肝脏和脾脏中马罗氏菌活菌计数显着减少。总而言之，我们的结果表明 LL-VapA 可以在鼻内免疫小鼠中激发基于 T(H)1 的保护性免疫反应。当与 LL-Lep 菌株共同给药时，这种反应会增强，而只有 LL-VapA 和 LL-Lep 共同给药才能在胃内接种疫苗的小鼠中诱导保护性免疫反应，与 T(H)1/T(H)2 细胞因子反应相关。 (C) 2011 Elsevier Ltd. 保留所有权利。
Rhodococcus equi causes severe pneumonia in foals and has recently gained attention as a significant opportunistic pathogen in immunocompromised humans. However, no effective vaccine to prevent rhodococcosis is currently available. In this study, we have engineered the food-grade bacterium Lactococcus fact is to secrete the virulence-associated protein A from R. equi (LL-VapA). The immunogenic potential of LL-VapA strain was then evaluated after either intragastric or intranasal immunization in mice either alone or in combination with LL-Lep, a recombinant strain of L. lactis secreting biologically active leptin, a pleiotropic hormone with significant immunomodulatory properties. Intragastric administration of LL-VapA led to the highest VapA-specific mucosal response whereas intranasal administration led to the highest systemic immune responses. Cytokines released from in vitro-stimulated spleen cells show both a strong IFN-gamma response and an increase of IL-4 level in all immunized groups, except for the group intranasally co-administered with both LL-VapA and LL-Lep. Strikingly, a significant reduction in R. equi viable counts in liver and spleen was observed four days after intravenous challenge with a virulent strain of R. equi in all immunized groups except for the group vaccinated by intragastric route with LL-VapA. Altogether, our results demonstrate that LL-VapA can evoke a T(H)1-based protective immune response in intranasally immunized mice. This response is enhanced when co-administered with LL-Lep strain, whereas only co-administration of LL-VapA and LL-Lep can induce a protective immune response in intragastric vaccinated mice, associated with a T(H)1/T(H)2 cytokine response. (C) 2011 Elsevier Ltd. All rights reserved.