Status of vaccine research and development for enterotoxigenic Escherichia coli
Status of vaccine research and development for enterotoxigenic Escherichia coli
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DOI：
10.1016/j.vaccine.2016.02.076
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发表时间：
2016-06-03
期刊：
影响因子：
5.5
通讯作者：
Walker, Richard I.
中科院分区：
文献类型：
--
作者：
Bourgeois, A. Louis;Wierzba, Thomas F.;Walker, Richard I.
产肠毒素大肠杆菌（ETEC）是导致大肠杆菌相关发病率和死亡率的最常见细菌原因之一，特别是在发展中国家的婴幼儿中。尽管如此，对儿童和旅行者健康的真正影响可能被低估了。目前没有针对ETEC的许可疫苗，但研究表明，通过接种疫苗进行免疫保护具有较高的公共卫生影响、成本效益和可行性。ETEC疫苗开发仍然是世界卫生组织的优先事项。传统上，ETEC疫苗的开发工作集中在诱导抗毒素和抗克隆抗原免疫，因为研究表明，针对这两种抗原类型的抗体都有助于保护，因此具有疫苗的潜力。领先的细胞疫苗候选物是ETVAX（四种灭活菌株的混合物）和ACE 527（三种活减毒菌株的混合物），这两种疫苗在I/II期试验中均被发现是安全的和免疫原性的。ETVAX是发展最快的沿着，孟加拉国已经在进行年龄下降的研究。基于蛋白质亚基、类毒素（LT和ST）或新的、更广泛保守的ETEC抗原的其他ETEC疫苗候选物也在开发中。其中，基于蛋白粘附素的亚基方法是最先进的。影响和经济模型表明，有利的疫苗成本效益，这可能有助于扩大市场对ETEC疫苗的兴趣。联合疫苗制剂可能有助于改善开发和使用的经济情况，更好的床旁诊断将有助于提高对ETEC真实健康负担的认识，并突出ETEC疫苗引入的潜在公共卫生益处。更好的诊断和疫苗需求预测也将改善疫苗开发融资，并在获得许可的疫苗上市后支持加速接种。(C)2016年世界卫生组织;许可证持有人Elsevier Ltd.
Enterotoxigenic Escherichia coli (ETEC) is one of the most common bacterial causes of diarrhea-associated morbidity and mortality, particularly among infants and young children in developing countries. Still, the true impact on child and traveler health is likely underestimated. There are currently no licensed vaccines for ETEC, but studies indicate high public health impact, cost-effectiveness, and feasibility of immune protection through vaccination. ETEC vaccine development remains a World Health Organization priority. Traditionally, ETEC vaccine development efforts have focused on inducing antitoxin and anticolonization antigen immunity, as studies indicate that antibodies against both antigen types can contribute to protection and thus have potential for vaccines. Leading cellular vaccine candidates are ETVAX (a mixture of four inactivated strains) and ACE527 (a mixture of three live attenuated strains), both of which have been found to be safe and immunogenic in Phase 1/2 trials. ETVAX is the furthest along in development with descending-age studies already underway in Bangladesh. Other ETEC vaccine candidates based on protein subunits, toxoids (both LT and ST), or novel, more broadly conserved ETEC antigens are also under development. Of these, a protein adhesin-based subunit approach is the most advanced. Impact and economic models suggest favorable vaccine cost-effectiveness, which may help expand market interest in ETEC vaccines. Combination vaccine formulations may help improve the economic case for development and use, and better point-of-care diagnostics will help to raise awareness of the true health burden of ETEC and highlight the potential public health benefit of ETEC vaccine introduction. Better diagnostics and vaccine demand forecasting will also improve vaccine development financing and support accelerated uptake once a licensed vaccine becomes available. (C) 2016 World Health Organization; licensee Elsevier Ltd.