Development of safe, effective and immunogenic vaccine candidate for diarrheagenic Escherichia coli main pathotypes in a mouse model.
Development of safe, effective and immunogenic vaccine candidate for diarrheagenic Escherichia coli main pathotypes in a mouse model.
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DOI：
10.1186/s13104-016-1891-z
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发表时间：
2016-02-09
影响因子：
1.8
通讯作者：
Amin, Magdy A
中科院分区：
文献类型：
--
作者：
Gohar, Asmaa;Abdeltawab, Nourtan F;Amin, Magdy A
背景：肠道和消化道疾病是发展中国家儿童死亡的重要原因。这些疾病导致全世界超过75万名5岁以下儿童死亡，在该年龄组中仅次于下呼吸道疾病，是第二大死亡原因。腹泻的主要病原体是大肠杆菌。有几个疫苗试验用于大肠杆菌。杆菌然而，大肠杆菌E.大肠杆菌有七种致病型，疫苗针对五种主要致病型中的一种或两种，导致腹泻。目前，市场上还没有针对所有五种大肠杆菌的联合疫苗。大肠杆菌致病型。因此，我们的目标是开发一种低成本的疫苗候选人结合五个主要的大肠杆菌。大肠杆菌提供广谱保护。我们配制了一种福尔马林灭活的肠聚集性、肠致病性、肠侵袭性、肠出血性和肠出血性大肠杆菌的全细胞混合物。结果：用10（9）CFU的联合疫苗候选物皮下免疫Balb/C小鼠，发现与未免疫对照组相比，攻击后存活率显著增加（100%存活）。接下来，我们旨在确定与每种致病型免疫相比，小鼠对组合疫苗候选物的免疫应答。为此，我们用联合疫苗候选物免疫小鼠组，并在6周内监测生物标志物水平，以及用相关活大肠杆菌攻击后测量应答。杆菌我们发现，与对照组相比，联合疫苗候选物引起的特异性全身抗体（IgG）、干扰素γ（IFN γ）和白细胞介素6（IL-6）水平显著升高，尤其是在免疫后的前2周（p
BACKGROUND: Enteric and diarrheal diseases are important causes of childhood death in the developing world. These diseases are responsible for more than 750 thousand deaths in children under 5years old worldwide, ranking second cause of death, after lower respiratory diseases, in this age group. Among the major causative agents of diarrhea is Escherichia coli. There are several vaccine trials for diarrheagenic E. coli. However, diarrheagenic E. coli has seven pathotypes and vaccines are directed for one or two of the five main pathotypes-causing diarrhea. Currently, there are no combined vaccines available in the market for all five diarrheagenic E. coli pathotypes. Therefore, we aimed to develop a low-cost vaccine candidate combining the five main diarrheagenic E. coli to offer wide-spectrum protection. We formulated a formalin-killed whole-cell mixture of enteroaggregative, enteropathogenic, enteroinvasive, enterohemorrhagic, and enterotoxigenic E. coli pathotypesas a combined vaccine candidate.RESULTS: We immunized Balb/C mice subcutaneously with 10(9) CFU of combined vaccine candidate and found a significant increase in survival ratepost challenge compared to unimmunized controls (100% survival). Next we aimed to determine the immunological response of mice to the combined vaccine candidate compared to each pathotype immunization. To do so, we immunized mice groups with combined vaccine candidate and monitored biomarkers levels over 6weeks as well as measured responses post challenge with relevant living E. coli. We found significant increase in specific systemic antibodies (IgG), interferon gamma (IFNgamma) and interleukin 6 (IL-6) levels elicited by combined vaccine candidate especially in the first 2weeks after mice immunization compared to controls (p