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DOI | 10.1038/ncomms15228 |
Oligomeric state of the ZIKV E protein defines protective immune responses | |
Metz, Stefan W.1; Thomas, Ashlie1; Brackbill, Alex2; Forsberg, John2; Miley, Michael J.2; Lopez, Cesar A.1; Lazear, Helen M.1; Tian, Shaomin1; de Silva, Aravinda M.1 | |
2019-10-10 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | The current leading Zika vaccine candidates in clinical testing are based on live or killed virus platforms, which have safety issues, especially in pregnant women. Zika subunit vaccines, however, have shown poor performance in preclinical studies, most likely because the antigens tested do not display critical quaternary structure epitopes present on Zika E protein homodimers that cover the surface of the virus. Here, we produce stable recombinant E protein homodimers that are recognized by strongly neutralizing Zika specific monoclonal antibodies. In mice, the dimeric antigen stimulate strongly neutralizing antibodies that target epitopes that are similar to epitopes recognized by human antibodies following natural Zika virus infection. The monomer antigen stimulates low levels of E-domain III targeting neutralizing antibodies. In a Zika challenge model, only E dimer antigen stimulates protective antibodies, not the monomer. These results highlight the importance of mimicking the highly structured flavivirus surface when designing subunit vaccines. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000489557600001 |
WOS关键词 | DOMAIN III ; ENVELOPE PROTEIN ; DENGUE VACCINE ; VIRUS ; ANTIBODIES ; DETERMINANTS ; TYPE-2 |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203284 |
专题 | 资源环境科学 |
作者单位 | 1.Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27515 USA; 2.Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27515 USA |
推荐引用方式 GB/T 7714 | Metz, Stefan W.,Thomas, Ashlie,Brackbill, Alex,et al. Oligomeric state of the ZIKV E protein defines protective immune responses[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Metz, Stefan W..,Thomas, Ashlie.,Brackbill, Alex.,Forsberg, John.,Miley, Michael J..,...&de Silva, Aravinda M..(2019).Oligomeric state of the ZIKV E protein defines protective immune responses.NATURE COMMUNICATIONS,10. |
MLA | Metz, Stefan W.,et al."Oligomeric state of the ZIKV E protein defines protective immune responses".NATURE COMMUNICATIONS 10(2019). |
条目包含的文件 | 条目无相关文件。 |
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