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-Structure paper
| タイトル | Defining bottlenecks and opportunities for Lassa virus neutralization by structural profiling of vaccine-induced polyclonal antibody responses. |
|---|---|
| ジャーナル・号・ページ | Cell Rep, Vol. 43, Issue 9, Page 114708, Year 2024 |
| 掲載日 | 2024年9月24日 |
 著者 | Philip J M Brouwer / Hailee R Perrett / Tim Beaumont / Haye Nijhuis / Sabine Kruijer / Judith A Burger / Ilja Bontjer / Wen-Hsin Lee / James A Ferguson / Martin Schauflinger / Helena Müller-Kräuter / Rogier W Sanders / Thomas Strecker / Marit J van Gils / Andrew B Ward /    |
| PubMed 要旨 | Lassa fever continues to be a major public health burden in West Africa, yet effective therapies or vaccines are lacking. The isolation of protective neutralizing antibodies against the Lassa virus ...Lassa fever continues to be a major public health burden in West Africa, yet effective therapies or vaccines are lacking. The isolation of protective neutralizing antibodies against the Lassa virus glycoprotein complex (GPC) justifies the development of vaccines that can elicit strong neutralizing antibody responses. However, Lassa vaccine candidates have generally been unsuccessful at doing so, and the associated antibody responses to these vaccines remain poorly characterized. Here, we establish an electron microscopy-based epitope mapping workflow that enables high-resolution structural characterization of polyclonal antibodies to the GPC. By applying this method to rabbits vaccinated with a recombinant GPC vaccine and a GPC-derived virus-like particle, we reveal determinants of neutralization that involve epitopes of the GPC-A competition cluster. Furthermore, by identifying undescribed immunogenic off-target epitopes, we expose the challenges that recombinant GPC vaccines face. By enabling detailed polyclonal antibody characterization, our work ushers in a next generation of more rational Lassa vaccine design. |
 リンク | Cell Rep / PubMed:39243373 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.8 - 25.0 Å |
| 構造データ | EMDB-41715, PDB-8tye: EMDB-43141, PDB-8vcv: EMDB-43168, PDB-8ve8:  EMDB-43174: GPCysRRLL-I53-50A in complex with rabbit 187 wk 30 GPC-A, base, and fusion peptide epitope pAbs  EMDB-43175: GPCysRRLL-I53-50A in complex with rabbit 187 wk 18 GPC-A, base, and fusion peptide epitope pAbs  EMDB-43176: GPCysRRLL-I53-50A in complex with rabbit 188 wk 30 base epitope pAbs  EMDB-43177: GPCysRRLL-I53-50A in complex with rabbit 189 wk 30 GPC-A and base epitope pAbs  EMDB-43178: GPCysRRLL-I53-50A in complex with rabbit 189 wk 18 GPC-A and base epitope pAbs  EMDB-43179: GPCysRRLL-I53-50A in complex with rabbit 190 wk 30 fusion peptide and base epitope pAbs  EMDB-43180: GPCysRRLL-I53-50A in complex with rabbit 191 wk 30 base epitope pAbs  EMDB-43181: GPCysRRLL-I53-50A in complex with rabbit 192 wk 30 base and fusion peptide epitope pAbs  EMDB-43182: GPCysRRLL-I53-50A in complex with base-targeting mAb LAVA05  EMDB-43183: GPCysRRLL-I53-50A in complex with base-targeting mAb LAVA06 EMDB-45624, PDB-9cj7: EMDB-45625, PDB-9cj8: EMDB-45643, PDB-9ck7: EMDB-45644, PDB-9ck8:  EMDB-45905: Lineage IV Lassa virus glycoprotein (Josiah) in complex with polyclonal antibody (Base-2 epitope) from rabbit 190 |
| 化合物 |  ChemComp-NAG: |
| 由来 |
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 キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / Lassa virus glycoprotein complex / GPC / immune complex / antibody / polyclonal antibody / base antibody / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / Lassa / GPC-C / glycoprotein / GP1-A / monoclonal antibody / 8.9F / LL-1 / GPC-A |
lassa virus josiah (ウイルス)
oryctolagus cuniculus (ウサギ)
thermotoga maritima (strain atcc 43589 / dsm 3109 / jcm 10099 / nbrc 100826 / msb8) (バクテリア)
homo sapiens (ヒト)