Protection against H1, H5, H6 and H9 influenza A infection with liposomal matrix 2 epitope vaccines

Protection against H1, H5, H6 and H9 influenza A infection with liposomal matrix 2 epitope vaccines
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DOI:
10.1016/j.vaccine.2006.04.008
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发表时间:
2006-06-12
期刊:
影响因子:
5.5
通讯作者:
Fujii, Gary
Fujii, Gary
中科院分区:
医学3区
文献类型:
--
作者:
Ernst, William A.;Kim, Hyung J.;Fujii, Gary

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最近出现了导致人类疾病的多种甲型禽流感病毒(即H5N1、H9N2和H7N7),加上人们担心其中一种毒株可能引发新的大流行,突显了开发新的免疫接种技术方法的必要性,以引发针对多种甲型流感病毒的保护性免疫反应。针对这一需求,利用一种新的基于脂质体的疫苗技术配制了几种与H1N1、H5N1和H9N2型流感病毒株相对应的基质2蛋白胞外结构域片段(M2eA),并被评估为潜在的免疫原,以开发一种“通用”的流感疫苗。用脂质体M2eA免疫的小鼠在H1N1(100%存活率)或H9N2(80%存活率)流感毒株的同源攻击中存活下来。他们的肺部病毒载量以及接受H5N1亚型攻击的免疫小鼠的肺病毒载量都显著降低。用与H1N1和H6N2相对应的M2eA片段(携带来自PR8/34的M2eA的重组甲型流感病毒)接种的小鼠,可诱导出针对该M2eA表位片段的高抗体效价,来自这些免疫小鼠的抗血清对接受致死剂量H6N2流感病毒的幼鼠提供了被动保护(100%存活)。这些结果首次证明了针对多亚型的重组M2eA抗原表位能诱导对同源挑战的免疫保护,并为基于M2eA的“通用”流感疫苗的开发提供了进一步的证据。(C)2006爱思唯尔有限公司。保留所有权利。
The recent emergence of multiple avian influenza A subtypes that cause human disease (i.e., H5N1, H9N2 and H7N7), coupled with the fear that one of these strains might precipitate a new pandemic, underscores the need to develop new technological approaches to immunization which elicit protective immune responses against multiple subtypes of influenza A. In response to this demand, several matrix 2 protein ectodomain segments (M2eA) corresponding to the H1N1, H5N1 and H9N2 influenza strains were formulated using a novel liposome-based vaccine technology and evaluated as potential immunogens for developing a "universal" influenza vaccine. Mice immunized with liposomal M2eA survived homologous challenges with H1N1 (100% survival) or H9N2 (80% survival) influenza strains. There were significant reductions in their lung viral load as well as in immunized mice challenged with the H5N1 subtype. The mice vaccinated with an M2eA segment corresponding to the H1N1 and H6N2 (a reassortant influenza A virus carrying the M2eA from PR8/34) strains elicited elevated IgG ELISA antibody titers to this M2eA epitope segment and antiserum from these immunized mice provided passive protection (100% survival) to naive mice receiving a lethal dose of H6N2 influenza virus. These results provide the first evidence that recombinant M2eA epitopes to multiple subtypes elicited immune protection against a homologous challenge and provides further evidence in favor of the development of a "universal" influenza vaccine based on M2eA. (c) 2006 Elsevier Ltd. All rights reserved.