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-Structure paper
タイトル | Vaccine design via antigen reorientation. |
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ジャーナル・号・ページ | Nat Chem Biol, Vol. 20, Issue 8, Page 1012-1021, Year 2024 |
掲載日 | 2024年1月15日 |
著者 | Duo Xu / Joshua J Carter / Chunfeng Li / Ashley Utz / Payton A B Weidenbacher / Shaogeng Tang / Mrinmoy Sanyal / Bali Pulendran / Christopher O Barnes / Peter S Kim / |
PubMed 要旨 | A major challenge in creating universal influenza vaccines is to focus immune responses away from the immunodominant, variable head region of hemagglutinin (HA-head) and toward the evolutionarily ...A major challenge in creating universal influenza vaccines is to focus immune responses away from the immunodominant, variable head region of hemagglutinin (HA-head) and toward the evolutionarily conserved stem region (HA-stem). Here we introduce an approach to control antigen orientation via site-specific insertion of aspartate residues that facilitates antigen binding to alum. We demonstrate the generalizability of this approach with antigens from Ebola, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses and observe enhanced neutralizing antibody responses in all cases. We then reorient an H2 HA in an 'upside-down' configuration to increase the exposure and immunogenicity of HA-stem. The reoriented H2 HA (reoH2HA) on alum induced stem-directed antibodies that cross-react with both group 1 and group 2 influenza A subtypes. Electron microscopy polyclonal epitope mapping (EMPEM) revealed that reoH2HA (group 1) elicits cross-reactive antibodies targeting group 2 HA-stems. Our results highlight antigen reorientation as a generalizable approach for designing epitope-focused vaccines. |
リンク | Nat Chem Biol / PubMed:38225471 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 15.1 - 24.7 Å |
構造データ | EMDB-42044: H2HA A/Japan/305/1957 complexed with mouse polyclonal Fab - wk 12, reoriented immunogen EMDB-42045: H2HA A/Japan/305/1957 complexed with mouse polyclonal Fab - wk 12, control immunogen EMDB-42046: H7N9 A/Shanghai/2/2013 complexed with mouse polyclonal Fab - wk 12, control immunogen EMDB-42048: H3N2 A/Victoria/3/1975 complexed with mouse polyclonal Fab - wk 7, control immunogen EMDB-42052: H3N2 A/Victoria/3/1975 complexed with mouse polyclonal Fab - wk 7, reoH2HA immunogen EMDB-42056: H7N9 A/Shanghai/2/2013 complexed with mouse polyclonal Fab - wk 7, reoriented immunogen EMDB-42058: H7N9 A/Shanghai/2/2013 complexed with mouse polyclonal Fab - wk 7, control immunogen EMDB-42059: H7N9 A/Shanghai/2/2013 complexed with mouse polyclonal Fab - wk 7, reoriented immunogen |
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