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DOI | 10.1038/s41467-018-03173-4 |
Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity | |
Pantophlet, Ralph1,2,3; Trattnig, Nino4; Murrell, Sasha5,6; Lu, Naiomi1; Chau, Dennis1; Rempel, Caitlin1; Wilson, Ian A.5,7,8; Kosma, Paul4,6 | |
2017-11-17 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | Canada; Austria; USA |
英文摘要 | Oligomannose-type glycans are among the major targets on the gp120 component of the HIV envelope protein (Env) for broadly neutralizing antibodies (bnAbs). However, attempts to elicit oligomannose-specific nAbs by immunizing with natural or synthetic oligomannose have so far not been successful, possibly due to B cell tolerance checkpoints. Here we design and synthesize oligomannose mimetics, based on the unique chemical structure of a recently identified bacterial lipooligosaccharide, to appear foreign to the immune system. One of these mimetics is bound avidly by members of a family of oligomannose-specific bnAbs and their putative common germline precursor when presented as a glycoconjugate. The crystal structure of one of the mimetics bound to a member of this bnAb family confirms the antigenic resemblance. Lastly, immunization of human-antibody transgenic animals with a lead mimetic evokes nAbs with specificities approaching those of existing bnAbs. These results provide evidence for utilizing antigenic mimicry to elicit oligomannose-specific bnAbs to HIV-1. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000415649900003 |
WOS关键词 | ENVELOPE GLYCOPROTEIN ; KNOCKOUT RATS ; B-CELLS ; BINDING ; 2G12 ; CARBOHYDRATE ; ADJUVANT ; GLYCANS ; ANTIGEN ; BEARING |
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/203696 |
专题 | 资源环境科学 |
作者单位 | 1.Simon Fraser Univ, Fac Hlth Sci, Burnaby, BC V5A 1S6, Canada; 2.Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada; 3.Simon Fraser Univ, SFU Interdisciplinary Res Ctr HIV, Burnaby, BC V5A 1S6, Canada; 4.Univ Nat Resources & Life Sci, Dept Chem, A-1190 Vienna, Austria; 5.Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA; 6.Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA; 7.Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA; 8.Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA |
推荐引用方式 GB/T 7714 | Pantophlet, Ralph,Trattnig, Nino,Murrell, Sasha,et al. Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Pantophlet, Ralph.,Trattnig, Nino.,Murrell, Sasha.,Lu, Naiomi.,Chau, Dennis.,...&Kosma, Paul.(2017).Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity.NATURE COMMUNICATIONS,8. |
MLA | Pantophlet, Ralph,et al."Bacterially derived synthetic mimetics of mammalian oligomannose prime antibody responses that neutralize HIV infectivity".NATURE COMMUNICATIONS 8(2017). |
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