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-Structure paper
| タイトル | Structural characterization of influenza group 1 chimeric hemagglutinins as broad vaccine immunogens. |
|---|---|
| ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 122, Issue 7, Page e2416628122, Year 2025 |
| 掲載日 | 2025年2月18日 |
著者 | Yen Thi Kim Nguyen / Xueyong Zhu / Julianna Han / Alesandra J Rodriguez / Weina Sun / Wenli Yu / Peter Palese / Florian Krammer / Andrew B Ward / Ian A Wilson / ![]() |
| PubMed 要旨 | Chimeric hemagglutinins (cHA) appear to be promising for the design and development of universal influenza vaccines. Influenza A group 1 cHAs, cH5/1, cH8/1, and cH11/1, comprising an H1 stem attached ...Chimeric hemagglutinins (cHA) appear to be promising for the design and development of universal influenza vaccines. Influenza A group 1 cHAs, cH5/1, cH8/1, and cH11/1, comprising an H1 stem attached to either an H5, H8, or H11 globular head, have been used sequentially as vaccine immunogens in human clinical trials and induced high levels of broadly protective antibodies. Using X-ray crystallography and negative-stain electron microscopy, we determined structures of cH5/1, cH8/1, and cH11/1 HAs in their apo (unliganded) and antibody Fab-bound states. Stem-reactive antibodies 3E1 and 31.b.09 recognize their cognate epitopes in cH5/1, cH8/1, and cH11/1 HAs. However, with cH5/1, the head domains are rotated by 35 to 45° around the threefold axis of the HA trimer compared to native HA with a more splayed-open conformation at the stem base. cH11/1 with 3E1 is structurally more native-like but resembles cH5/1 with 31.b.09, whereas cH8/1 with 31.b.09 exhibited a range of closed-to-open stem configurations with some separation of head and stem domains. Furthermore, all of these group 1 cHAs effectively bound a broad head trimer interface antibody and other broad stem antibodies. Thus, the cHAs exhibit structural plasticity without compromising the stem and head trimer interface epitopes for elicitation of influenza A group 1 cross-reactive antibodies. |
リンク | Proc Natl Acad Sci U S A / PubMed:39937865 / PubMed Central |
| 手法 | EM (単粒子) / X線回折 |
| 解像度 | 3.5 - 20.0 Å |
| 構造データ | ![]() EMDB-46833: Negative stain map of cH5/1 apo ![]() EMDB-46834: Negative stain map of cH11/1 closed apo ![]() EMDB-46835: Negative stain of cH5/1 HA in complex with 31.b.09 Fab ![]() EMDB-46836: Negative stain of cH5/1 HA in complex with CR9114 Fab ![]() EMDB-46837: Negative stain of cH11/1 HA in complex with 31.b.09 Fab ![]() EMDB-46838: Negative stain of cH8/1 HA in complex with 31.b.09 Fab ![]() EMDB-46839: Negative stain map of cH8/1 HA in complex with CR9114 Fab ![]() EMDB-46840: Negative stain of cH5/1 HA in complex with FluA20 fab ![]() EMDB-46841: Negative stain of cH8/1 HA in complex with FluA20 Fab ![]() EMDB-46842: Negative stain maps of cH8/1 apo HA ![]() PDB-9c0u: ![]() PDB-9c0v: ![]() PDB-9c0x: ![]() PDB-9c22: |
| 化合物 | ![]() ChemComp-NAG: |
| 由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / immune system / VIRAL PROTEIN-IMMUNE SYSTEM complex |
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Influenza A virus (A/California/04/2009(H1N1)) (A型インフルエンザウイルス)
homo sapiens (ヒト)
influenza a virus (A型インフルエンザウイルス)
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