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-Structure paper
Title | Immune memory shapes human polyclonal antibody responses to H2N2 vaccination. |
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Journal, issue, pages | bioRxiv, Year 2023 |
Publish date | Aug 24, 2023 |
![]() | 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. |
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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: |
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