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TitleStructural serology of polyclonal antibody responses to mRNA-1273 and NVX-CoV2373 COVID-19 vaccines.
Journal, issue, pagesbioRxiv, Year 2024
Publish dateDec 12, 2024
AuthorsSandhya Bangaru / Abigail M Jackson / Jeffrey Copps / Monica L Fernández-Quintero / Jonathan L Torres / Sara T Richey / Bartek Nogal / Leigh M Sewall / Alba Torrents de la Peña / Asma Rehman / Mimi Guebre-Xabier / Bethany Girard / Rituparna Das / Kizzmekia S Corbett-Helaire / Robert A Seder / Barney S Graham / Darin K Edwards / Nita Patel / Gale Smith / Andrew B Ward /
PubMed AbstractCurrent COVID-19 vaccines are largely limited in their ability to induce broad, durable immunity against emerging viral variants. Design and development of improved vaccines utilizing existing ...Current COVID-19 vaccines are largely limited in their ability to induce broad, durable immunity against emerging viral variants. Design and development of improved vaccines utilizing existing platforms requires an in-depth understanding of the antigenic and immunogenic properties of available vaccines. Here we examined the antigenicity of two of the original COVID-19 vaccines, mRNA-1273 and NVX-CoV2373, by electron microscopy-based polyclonal epitope mapping (EMPEM) of serum from immunized non-human primates (NHPs) and clinical trial donors. Both vaccines induce diverse polyclonal antibody (pAb) responses to the N-terminal domain (NTD) in addition to the receptor-binding domain (RBD) of the Spike protein, with the NTD supersite being an immunodominant epitope. High-resolution cryo-EMPEM studies revealed extensive pAb responses to and around the supersite with unique angles of approach and engagement. NTD supersite pAbs were also the most susceptible to variant mutations compared to other specificities, indicating that ongoing Spike ectodomain-based vaccine design strategies should consider immuno-masking this site to prevent induction of these strain-specific responses.
External linksbioRxiv / PubMed:39713412 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 4.5 Å
Structure data

EMDB-48188: SARS-CoV-2 Wuhan Spike ectodomain in complex with human polyclonal antibody ModWu-RBD1 (mRNA-1273 vaccine)
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-48189: SARS-CoV-2 Wuhan Spike ectodomain in complex with human polyclonal antibody ModWu-RBD2 (mRNA-1273 vaccine)
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-48190: SARS-CoV-2 Wuhan Spike ectodomain in complex with human polyclonal antibody ModWu-NTD1 (mRNA-1273 vaccine)
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-48192: SARS-CoV-2 Wuhan Spike ectodomain in complex with human polyclonal antibody ModWu-NTD2 (mRNA-1273 vaccine)
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-48193: SARS-CoV-2 Wuhan Spike ectodomain in complex with human polyclonal antibody ModWu-NTD3 (mRNA-1273 vaccine)
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-48194: SARS-CoV-2 Wuhan Spike ectodomain in complex with human polyclonal antibody ModWu-NTD4 (mRNA-1273 vaccine)
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-48195: SARS-CoV-2 Wuhan Spike ectodomain in complex with human polyclonal antibody ModWu-NTD5 (mRNA-1273 vaccine)
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-48196: SARS-CoV-2 Wuhan Spike ectodomain in complex with human polyclonal antibody ModWu-NTD6 (mRNA-1273 vaccine)
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-48197: SARS-CoV-2 Delta Spike ectodomain in complex with human polyclonal antibody ModDe-RBD1 (mRNA-1273 vaccine)
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-48198: SARS-CoV-2 Delta Spike ectodomain in complex with human polyclonal antibody ModDe-NTD1 (mRNA-1273 vaccine)
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-48199: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPWu1 (NVX-CoV2373 vaccine)
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-48200: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPWu2 (NVX-CoV2373 vaccine)
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-48201: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPWu3 (NVX-CoV2373 vaccine)
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-48202: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPWu4 (NVX-CoV2373 vaccine)
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-48203: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPWu5 (NVX-CoV2373 vaccine)
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-48204: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPWu6 (NVX-CoV2373 vaccine)
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-48205: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPWu7 (NVX-CoV2373 vaccine)
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-48206: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPSA1 (NVX-CoV2373/rS-Beta immunized)
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-48207: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPSA2 (NVX-CoV2373/rS-Beta immunized)
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-48208: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPSA3 (NVX-CoV2373/rS-Beta immunized)
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-48209: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPSA4 (NVX-CoV2373/rS-Beta immunized)
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-48210: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPSA5 (NVX-CoV2373/rS-Beta immunized)
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-48211: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPSA6 (NVX-CoV2373/rS-Beta immunized)
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-48212: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPSA7 (NVX-CoV2373/rS-Beta immunized)
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-48213: SARS-CoV-2 Wuhan Spike ectodomain in complex with NHP polyclonal antibody NVX-NHPSA8 (NVX-CoV2373/rS-Beta immunized)
Method: EM (single particle) / Resolution: 4.4 Å

Source
  • Severe acute respiratory syndrome coronavirus 2
  • Homo sapiens (human)

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