Shigella IpaB and IpaD displayed on L. lactis bacterium-like particles induce protective immunity in adult and infant mice.
Shigella IpaB and IpaD displayed on L. lactis bacterium-like particles induce protective immunity in adult and infant mice.
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DOI：
10.1038/icb.2015.24
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发表时间：
2015-08
影响因子：
4
通讯作者：
Pasetti MF
中科院分区：
文献类型：
--
作者：
Heine SJ;Franco-Mahecha OL;Chen X;Choudhari S;Blackwelder WC;van Roosmalen ML;Leenhouts K;Picking WL;Pasetti MF
志贺氏菌属是流行地区 5 岁以下儿童中重度腹泻发病率最高的肠道病原体之一。没有疫苗可以预防这种疾病。在这项工作中，我们研究了一种新的志贺氏菌疫苗概念，该概念由非活体、自佐剂、乳酸乳球菌类细菌颗粒 (BLP) 组成，展示志贺氏菌入侵质粒抗原 (Ipa) B 和 IpaD，并检查了其对通过鼻腔途径免疫的成年和新生/婴儿小鼠的免疫原性和保护功效。这种方法的独特优势包括由于 Ipa 的高度保守结构而具有广泛保护的潜力，以及基于益生菌的粘膜/佐剂递送平台的安全性和实用性。用 BLP-IpaB 和 BLP-IpaD (BLP-IpaB/D) 免疫成年小鼠，以剂量依赖性方式诱导高水平的 Ipa 特异性血清 IgG 和粪便 IgA。 BLP 递送增强了免疫反应和保护。疫苗诱导的血清抗体表现出调理吞噬和细胞毒性中和活性，并且 IpaB/D IgG 滴度与攻击后存活率的增加相关。在鼻组织和肺部检测到 Ipa 特异性抗体分泌细胞，在支气管肺泡灌洗液中检测到 IgG。骨髓细胞产生 IpaB/D 特异性抗体，有助于过继转移后的保护。 BLP-IpaB/D 疫苗对弗氏沙门氏菌和宋内沙门氏菌分别具有 90% 和 80% 的保护作用。新生儿时接受 BLP-IpaB/D 免疫的小鼠也产生了 IpaB 和 IpaD 血清抗体； 90% 的人受到福氏链球菌的保护，44% 的人免受宋内链球菌的影响。 BLP-IpaB/D 疫苗是一种有希望的候选疫苗，可以安全、实用且可能有效地对儿童进行志贺氏菌病免疫。
Shigella spp. are among the enteric pathogens with the highest attributable incidence of moderate-to-severe diarrhea in children under 5 years of age living in endemic areas. There are no vaccines available to prevent this disease. In this work, we investigated a new Shigella vaccine concept consisting of non-living, self-adjuvanted, Lactococcus lactis bacterium-like particles (BLP) displaying Shigella invasion plasmid antigen (Ipa) B and IpaD and examined its immunogenicity and protective efficacy in adult and newborn/infant mice immunized via the nasal route. Unique advantages of this approach include the potential for broad protection due to the highly conserved structure of the Ipas and the safety and practicality of a probiotic-based mucosal/adjuvant delivery platform. Immunization of adult mice with BLP-IpaB and BLP-IpaD (BLP-IpaB/D) induced high levels of Ipa-specific serum IgG and stool IgA in a dose-dependent manner. Immune responses and protection were enhanced by BLP delivery. Vaccine-induced serum antibodies exhibited opsonophagocytic and cytotoxic neutralizing activity, and IpaB/D IgG titers correlated with increased survival post-challenge. Ipa-specific antibody secreting cells were detected in nasal tissue and lungs, as well as IgG in bronchoalveolar lavage. Bone marrow cells produced IpaB/D-specific antibodies and contributed to protection after adoptive transfer. The BLP-IpaB/D vaccine conferred 90% and 80% protection against S. flexneri and S. sonnei, respectively. Mice immunized with BLP-IpaB/D as newborns also developed IpaB and IpaD serum antibodies; 90% were protected against S. flexneri and 44% against S. sonnei. The BLP-IpaB/D vaccine is a promising candidate for safe, practical and potentially effective immunization of children against shigellosis.