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DOI | 10.1038/s41467-018-07013-3 |
Structure-based design of chimeric antigens for multivalent protein vaccines | |
Hollingshead, S.1; Jongerius, I.1,2; Exley, R. M.1; Johnson, S.1; Lea, S. M.1; Tang, C. M.1 | |
2018-03-13 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | England; Netherlands |
英文摘要 | There is an urgent need to develop vaccines against pathogenic bacteria. However, this is often hindered by antigenic diversity and difficulties encountered manufacturing membrane proteins. Here we show how to use structure-based design to develop chimeric antigens (ChAs) for subunit vaccines. ChAs are generated against serogroup B Neisseria meningitidis (MenB), the predominant cause of meningococcal disease in wealthy countries. MenB ChAs exploit factor H binding protein (fHbp) as a molecular scaffold to display the immunogenic VR2 epitope from the integral membrane protein PorA. Structural analyses demonstrate fHbp is correctly folded and the PorA VR2 epitope adopts an immunogenic conformation. In mice, immunisation with ChAs generates fHbp and PorA antibodies that recognise the antigens expressed by clinical MenB isolates; these antibody responses correlate with protection against meningococcal disease. Application of ChAs is therefore a potentially powerful approach to develop multivalent subunit vaccines, which can be tailored to circumvent pathogen diversity. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000427247900009 |
WOS关键词 | OUTER-MEMBRANE PROTEIN ; B MENINGOCOCCAL VACCINE ; FACTOR-H BINDING ; NEISSERIA-MENINGITIDIS ; VESICLE VACCINE ; SEROGROUP-B ; BACTERICIDAL ANTIBODIES ; EPITOPE-SCAFFOLDS ; CRYSTAL-STRUCTURE ; IMMUNE-RESPONSE |
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/204072 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Oxford, Sir William Dunn Sch Pathol, South Parks Rd, Oxford OX1 3RE, England; 2.Univ Med Ctr Utrecht, Dept Med Microbiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands |
推荐引用方式 GB/T 7714 | Hollingshead, S.,Jongerius, I.,Exley, R. M.,et al. Structure-based design of chimeric antigens for multivalent protein vaccines[J]. NATURE COMMUNICATIONS,2018,9. |
APA | Hollingshead, S.,Jongerius, I.,Exley, R. M.,Johnson, S.,Lea, S. M.,&Tang, C. M..(2018).Structure-based design of chimeric antigens for multivalent protein vaccines.NATURE COMMUNICATIONS,9. |
MLA | Hollingshead, S.,et al."Structure-based design of chimeric antigens for multivalent protein vaccines".NATURE COMMUNICATIONS 9(2018). |
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