A multi-epitope fusion antigen candidate vaccine for Enterotoxigenic Escherichia coli is protective against strain B7A colonization in a rabbit model.
A multi-epitope fusion antigen candidate vaccine for Enterotoxigenic Escherichia coli is protective against strain B7A colonization in a rabbit model.
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DOI：
10.1371/journal.pntd.0010177
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发表时间：
2022-03
影响因子：
3.8
通讯作者：
Sack DA
中科院分区：
文献类型：
--
作者：
Jones RM Jr;Seo H;Zhang W;Sack DA
产肠毒素大肠杆菌(ETEC)菌株是引起儿童和旅行者腹泻的主要原因。开发针对这一异源群体的有效疫苗已被证明是困难的，因为决定其病理的毒素和粘附素的性质各不相同。利用多表位融合抗原(MEFA)疫苗学平台开发了一种多价候选疫苗，并被证明在小鼠和猪中有效地诱导了广泛的保护性抗体反应。然而，在这些系统中并没有测量到对ETEC在小肠的定植的直接保护。ETEC菌株的定植是已知的疾病结局的决定因素，并且是粘附素依赖的。在本研究中，我们建立了一种非手术的兔定植模型，以研究ETEC在兔体内定植的免疫保护作用。我们测试了基于MEFA的疫苗粘附素抗原与dmLT佐剂联合使用的能力，以诱导广泛的免疫反应，并防止ETEC在兔小肠的定植。我们的结果表明，候选疫苗MEFA抗原在兔体内诱导对其结构中包括的七种粘附素发生反应的抗体，并防止持续在幼兔身上定植的挑战菌株的定植。腹泻病仍然是世界各地的主要健康威胁。产肠毒素大肠杆菌(ETEC)是一组细菌，是旅行者和五岁以下儿童腹泻疾病的主要原因之一。ETEC的一个特征是用于定植哺乳动物肠道的各种表面蛋白。我们已经开发出一种称为多表位融合抗原(MEFA)的单一蛋白疫苗候选，它能在小鼠和猪身上诱导针对七种不同定植因子的抗体产生。在这里，我们利用ETEC定植的兔模型来确定这种MEFA免疫是否可以提供直接保护，防止小肠定植。我们的结果表明，用候选疫苗免疫兔子会产生与其结构中包括的七种定植因子结合的抗体，并防止持续定植未接种疫苗的兔的挑战菌株的定植。这项研究提供了更多的证据来支持MEFA的战略，即为ETEC和其他不同的肠道病原体产生广泛保护的疫苗。
Enterotoxigenic Escherichia coli (ETEC) strains are a leading cause of children’s and travelers’ diarrhea. Developing effective vaccines against this heterologous group has proven difficult due to the varied nature of toxins and adhesins that determine their pathology. A multivalent candidate vaccine was developed using a multi-epitope fusion antigen (MEFA) vaccinology platform and shown to effectively elicit broad protective antibody responses in mice and pigs. However, direct protection against ETEC colonization of the small intestine was not measured in these systems. Colonization of ETEC strains is known to be a determining factor in disease outcomes and is adhesin-dependent. In this study, we developed a non-surgical rabbit colonization model to study immune protection against ETEC colonization in rabbits. We tested the ability for the MEFA-based vaccine adhesin antigen, in combination with dmLT adjuvant, to induce broad immune responses and to protect from ETEC colonization of the rabbit small intestine. Our results indicate that the candidate vaccine MEFA antigen elicits antibodies in rabbits that react to seven adhesins included in its construction and protects against colonization of a challenge strain that consistently colonized naïve rabbits. Diarrheal diseases remain a major health threat around the world. Enterotoxigenic E. coli (ETEC) are a group of bacteria that are among the leading causes of diarrheal disease in travelers and children under five. One characteristic of ETEC are the diverse surface proteins used to colonize the gut of mammals. We have developed a single protein vaccine candidate called a multi-epitope fusion antigen (MEFA) that elicits antibody production in mice and pigs against seven diverse colonization factors. Here, we took advantage of a rabbit model of ETEC colonization to determine if immunization with this MEFA can provide direct protection against colonization of the small intestine. Our results indicate that immunization of rabbits with the candidate vaccine elicits antibodies that bind to seven colonization factors included in its construction and protects against colonization of a challenge strain that consistently colonized unvaccinated rabbits. This study provides additional evidence to support the MEFA strategy for generating a broadly protective vaccine for ETEC and other diverse enteric pathogens.
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影响因子：
56.3
作者：
Qadri, Firdausi;Akhtar, Marjahan;Svennerholm, Ann-Mari
通讯作者：
Svennerholm, Ann-Mari
影响因子：
5.5
作者：
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通讯作者：
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影响因子：
168.9
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通讯作者：
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影响因子：
3.7
作者：
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通讯作者：
Zhang W
影响因子：
3.1
作者：
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通讯作者：
Zhang, Weiping