...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Vaccine >Identification of HLA class II H5N1 hemagglutinin epitopes following subvirion influenza A (H5N1) vaccination
【24h】

Identification of HLA class II H5N1 hemagglutinin epitopes following subvirion influenza A (H5N1) vaccination

机译：甲型亚流感病毒（H5N1）疫苗接种后HLA II类H5N1血凝素表位的鉴定

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Prophylactic immunization against influenza infection requires CD4+ T-helper cell activity for optimal humoral and cellular immunity. Currently there is one FDA approved H5N1 subvirion vaccine available, although stockpiles of this vaccine are insufficient for broad population coverage and the vaccine has only demonstrated modest immunogenicity. Specific activation of CD4+ T-helper cells using class II H5N1 HA peptide vaccines may be a useful component in immunization strategy and design. Identification of HLA class II HA epitopes was undertaken in this report by obtaining PBMCs from volunteers previously immunized with an H5N1 inactivated subvirion vaccine, followed by direct ex vivo stimulation of CD4+ T cells against different sources of potential HA class II epitopes. In the 1st round of analysis, 35 donors were tested via IFN-gamma ELISPOT using pools of overlapping HA peptides derived from the H5N1 A/Thailand/4(SP-528)/2004 virus, recombinant H5N1 (rHA) and inactivated H5N1 subvirion vaccine. In addition, a series of algorithm-predicted epitopes coupled with the Ii-Key moiety of the MHC class II-associated invariant chain for enhanced MHC class II charging were also included. Specific responses were observed for all 20 peptide pools, with 6-26% of vaccinated individuals responding to any given pool (donor response frequency) and a magnitude of response ranging from 3- to > 10-fold above background levels. Responses were similarly observed with the majority of algorithm-predicted epitopes, with a donor response frequency of up to 29% and a magnitude of response ranging from 3-10-fold (11/24 peptides) to > 10-fold above background (7/24 peptides). PBMCs from vaccine recipients that had detectable responses to H5N1 rHA following 1st round analysis were used in a 2nd round of testing to confirm the identity of specific peptides based on the results of the 1st screening. Sixteen individual HA peptides identified from the library elicited CD4+ T cell responses between 3- and > 10-fold above background, with two peptides being recognized in 21% of recipients tested. Eight of the putative MHC class II epitopes recognized were found in regions showing partial to significant sequence homology with New Caledonia H1N1 influenza HA, while eight were unique to H5N1 HA. This is the first study to identify H5N1 HA epitope-specific T cells in vaccine recipients and offers hope for the design of a synthetic peptide vaccine to prime CD4+ T-helper cells. Such a vaccine could be used to provide at least some minimal level of H5N1 protection on its own and/or prime for a subsequent dose of a more traditional but supply-limited vaccine.
机译：针对流感感染的预防性免疫需要CD4 + T辅助细胞活性才能获得最佳的体液和细胞免疫。目前，有一种FDA批准的H5N1亚病毒颗粒疫苗可供使用，尽管该疫苗的库存不足以覆盖广泛的人群，并且该疫苗仅显示了适度的免疫原性。使用II类H5N1 HA肽疫苗特异性激活CD4 + T辅助细胞可能是免疫策略和设计中的有用组成部分。通过从先前用H5N1灭活的亚病毒疫苗免疫的志愿者那里获得PBMC，然后直接针对不同来源的潜在HA II类抗原表位对CD4 + T细胞进行离体刺激，在本报告中鉴定了HLA II类HA表位。在第一轮分析中，使用源自H5N1 A / Thailand / 4（SP-528）/ 2004病毒，重组H5N1（rHA）和灭活的H5N1亚病毒疫苗的重叠HA肽库，通过IFN-γELISPOT测试了35个供体。另外，还包括一系列算法预测的表位，以及与MHC II类相关的不变链的Ii-Key部分偶联，以增强II类MHC的电荷。在所有20个肽库中均观察到了特异性反应，其中6-26％的疫苗接种个体对任何给定的库均有反应（供体反应频率），反应幅度比背景水平高3至10倍。在大多数算法预测的表位上也观察到了类似的反应，供体反应频率高达29％，反应幅度为背景的3-10倍（11/24肽）到背景背景的10倍以上（7）。 / 24肽）。在第一轮分析后，将来自疫苗接受者的对H5N1 rHA有可检测反应的PBMC用于第二轮测试，以基于第一次筛选的结果确认特定肽的身份。从文库中鉴定出的16种单独的HA肽引起CD4 + T细胞应答比背景高3到> 10倍，其中有21％的受体识别出2种肽。在与新喀里多尼亚H1N1流感HA部分或显着的序列同源性的区域中发现了公认的II类MHC II表位中的8个，而H5N1 HA独有。这是鉴定疫苗接受者中H5N1 HA表位特异性T细胞的第一项研究，并为设计用于引发CD4 + T辅助细胞的合成肽疫苗提供了希望。对于随后剂量的更传统但供应有限的疫苗，此类疫苗可单独和/或初次用于提供至少一些最低水平的H5N1保护。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号