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-Structure paper
タイトル | Immune memory shapes human polyclonal antibody responses to H2N2 vaccination. |
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ジャーナル・号・ページ | bioRxiv, Year 2023 |
掲載日 | 2023年8月24日 |
著者 | Yuhe R Yang / Julianna Han / Hailee R Perrett / Sara T Richey / Abigail M Jackson / Alesandra J Rodriguez / Rebecca A Gillespie / Sarah O'Connell / Julie E Raab / Lauren Y Cominsky / Ankita Chopde / Masaru Kanekiyo / Katherine V Houser / Grace L Chen / Adrian B McDermott / Sarah F Andrews / Andrew B Ward / |
PubMed 要旨 | Influenza A virus subtype H2N2, which caused the 1957 influenza pandemic, remains a global threat. A recent phase I clinical trial investigating a ferritin nanoparticle displaying H2 hemagglutinin in ...Influenza A virus subtype H2N2, which caused the 1957 influenza pandemic, remains a global threat. A recent phase I clinical trial investigating a ferritin nanoparticle displaying H2 hemagglutinin in H2-naïve and H2-exposed adults. Therefore, we could perform comprehensive structural and biochemical characterization of immune memory on the breadth and diversity of the polyclonal serum antibody response elicited after H2 vaccination. We temporally map the epitopes targeted by serum antibodies after first and second vaccinations and show previous H2 exposure results in higher responses to the variable head domain of hemagglutinin while initial responses in H2-naïve participants are dominated by antibodies targeting conserved epitopes. We use cryo-EM and monoclonal B cell isolation to describe the molecular details of cross-reactive antibodies targeting conserved epitopes on the hemagglutinin head including the receptor binding site and a new site of vulnerability deemed the medial junction. Our findings accentuate the impact of pre-existing influenza exposure on serum antibody responses. |
リンク | bioRxiv / PubMed:37781590 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.8 - 22.8 Å |
構造データ | EMDB-41464, PDB-8tp2: EMDB-41465, PDB-8tp3: EMDB-41466, PDB-8tp4: EMDB-41467, PDB-8tp5: EMDB-41468, PDB-8tp6: EMDB-41469, PDB-8tp7: EMDB-41470, PDB-8tp9: EMDB-41471, PDB-8tpa: EMDB-41472: H2 hemagglutinin (A/Singapore/1/1957) in complex with polyclonal Fab, pAb_1 EMDB-41473: H2 hemagglutinin (A/Singapore/1/1957) in complex with polyclonal Fab, pAb_2 EMDB-41474: H2 hemagglutinin (A/Singapore/1/1957) in complex with polyclonal Fab, pAb_3 EMDB-41523: Polyclonal immune complex of Fab binding the H2 HA from serum of subject 2-1 at week 4 EMDB-41524: Polyclonal immune complex of Fab binding the H2 HA from serum of subject 2-1 at week 16 EMDB-41525: Polyclonal immune complex of Fab binding the H2 HA from serum of subject 2-1 at week 20 EMDB-41526: Polyclonal immune complex of Fab binding the H2 HA from serum of subject 2-2 at week 0 EMDB-41527: Polyclonal immune complex of Fab binding the H2 HA from serum of subject 2-2 at week 4 EMDB-41528: Polyclonal immune complex of Fab binding the H2 HA from serum of subject 2-2 week 16 EMDB-41529: Polyclonal immune complex of Fab binding to H2 HA from serum of subject 2-2 at week 20 EMDB-41530: Polyclonal immune complex of Fab binding the H2 HA from serum of subject 2-3 at week 4 EMDB-41531: Polyclonal immune complex of Fab binding H2 HA from serum of subject 2-3 at week 16 EMDB-41683: H2 HA in complex with Cb-targeting mAb 2-2-1E08 EMDB-41684: H2 HA in complex with esterase-targeting mAb 2-2-1C06 EMDB-41685: H2 HA in complex with RBS-targeting mAb 4-1-1E02 EMDB-41686: H2 HA in complex with Sa-targeting mAb 4-1-1G03 EMDB-41687: H2 HA in complex with Sa/Sb-targeting mAb 1-3-1F08 EMDB-41688: H2 HA in complex with RBS-targeting mAb 1-1-1F05 EMDB-41689: H2 HA in complex with Sa/Sb-targeting mAb 2-2-1F01 EMDB-41690: H2 HA in complex with medial-junction-targeting mAb 2-2-1G06 EMDB-41691: H2 HA in complex with RBS-targeting mAb 1-2-189-34 EMDB-41692: H2 HA in complex with RBS-targeting mAb 1-1-1A09 EMDB-41693: H2 HA in complex with RBS-targeting mAb 1-1-2A11 EMDB-41694: H2 HA in complex with Sb-targeting mAb 1-1-2E05 |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN/Immune System / influenza / hemagglutinin / monoclonal antibody / immune complex / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex |