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| Title | Immune memory shapes human polyclonal antibody responses to H2N2 vaccination. |
|---|---|
| Journal, issue, pages | bioRxiv, Year 2023 |
| Publish date | Aug 24, 2023 |
 Authors | 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 Abstract | 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. |
 External links | bioRxiv / PubMed:37781590 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.8 - 22.8 Å |
| Structure data | 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-41560: Polyclonal immune complex of Fab binding the H1 HA from serum of subject 1-1 at week 20  EMDB-41561: Polyclonal immune complex of Fab binding the H1 HA from serum of subject 2-2 at week 0  EMDB-41562: Polyclonal immune complex of Fab binding the H1 HA from serum of subject 2-2 at week 4  EMDB-41563: Polyclonal immune complex of Fab binding the H1 HA from serum of subject 2-2 at week 16  EMDB-41564: Polyclonal immune complex of Fab binding the H1 HA from serum of subject 2-2 at week 20  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 |
| Chemicals |  ChemComp-NAG: |
| Source |
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 Keywords |  VIRAL PROTEIN/Immune System / influenza / hemagglutinin / monoclonal antibody / immune complex / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex |
