Delivery of woodchuck hepatitis virus-like particle presented influenza M2e by recombinant attenuated Salmonella displaying a delayed lysis phenotype.
Delivery of woodchuck hepatitis virus-like particle presented influenza M2e by recombinant attenuated Salmonella displaying a delayed lysis phenotype.
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DOI：
10.1016/j.vaccine.2010.07.083
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发表时间：
2010-09-24
期刊：
影响因子：
5.5
通讯作者：
Curtiss, Roy, III
中科院分区：
文献类型：
--
作者：
Ameiss, Keith;Ashraf, Shamaila;Kong, Wei;Pekosz, Andrew;Wu, Wai-Hong;Milich, David;Billaud, Jean-Noel;Curtiss, Roy, III
使用重组减毒沙门氏菌活疫苗（RASV）是控制多种病原体感染的一种很有前途的方法。流感M2蛋白（M2e）的高度保守的细胞外结构域已被证明对具有相似M2e序列的多种流感亚型提供广谱保护。将许多禽流感亚型共有的M2e表位插入土拨鼠肝炎病毒的核心抗原中，并在两种不同的减毒鼠伤寒沙门菌重组株中表达。其中一株通过删除cya和crp基因而减毒。第二种菌株被设计成具有程序性延迟裂解表型。这两种菌株都能产生单体融合蛋白和完全组装的核心颗粒。用延迟裂解的菌株口服免疫小鼠，其抗体滴度明显高于Δcya Δcrp菌株，并且对表达禽病毒常见M2e序列的a /WSN/33流感病毒低水平攻击具有中等保护作用。进一步的研究表明，表达核心抗原的沙门氏菌诱导的抗体水平与注射明矾佐剂的纯化核心抗原相当，两者都能够减少病毒在肺部的复制。据我们所知，这是第一份证明沙门氏菌介导的流感病毒M2e蛋白在哺乳动物宿主中的传递可诱导针对病毒攻击的保护性免疫反应的报告。
The use of live recombinant attenuated Salmonella vaccines (RASV) is a promising approach for controlling infections by multiple pathogens. The highly conserved extracellular domain of the influenza M2 protein (M2e) has been shown to provide broad spectrum protection against multiple influenza subtypes sharing similar M2e sequences. An M2e epitope common to a number of avian influenza subtypes was inserted into the core antigen of woodchuck hepatitis virus and expressed in two different recombinant attenuated Salmonella Typhimurium strains. One strain was attenuated via deletion of the cya and crp genes. The second strain was engineered to exhibit a programmed delayed lysis phenotype. Both strains were able to produce both monomeric fusion proteins and fully assembled core particles. Mice orally immunized with the strain exhibiting delayed lysis induced significantly greater antibody titers than the Δcya Δcrp strain and provided moderate protection against weight loss to a low level challenge with the influenza strain A/WSN/33 modified to express the M2e sequence common to avian viruses. Further studies indicated that the Salmonella expressed core antigen induced comparable antibody levels to the purified core antigen injected with an alum adjuvant and that both are able to reduce viral replication in the lungs. To our knowledge this is the first report demonstrating Salmonella-mediated delivery of influenza virus M2e protein in a mammalian host to induce a protective immune response against viral challenge.
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