EMD-48194
SARS-CoV-2 Wuhan Spike ectodomain in complex with human polyclonal antibody ModWu-NTD4 (mRNA-1273 vaccine)
EMD-48194
Single-particle3.7 Å
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Map released: 22/01/2025
Last modified: 22/01/2025
Sample Organism:
Severe acute respiratory syndrome coronavirus 2,
Homo sapiens
Sample: SARS-CoV-2 Wuhan spike ectodomain in complex with human polyclonal antibody ModWu-NTD4
Deposition Authors: Bangaru S
,
Jackson AM
,
Ward AB
Sample: SARS-CoV-2 Wuhan spike ectodomain in complex with human polyclonal antibody ModWu-NTD4
Deposition Authors: Bangaru S
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Structural serology of polyclonal antibody responses to mRNA-1273 and NVX-CoV2373 COVID-19 vaccines.
Bangaru S
,
Jackson AM
,
Copps J
,
Fernandez-Quintero ML,
Torres JL
,
Richey ST
,
Nogal B
,
Sewall LM
,
de la Pena AT
,
Rehman A
,
Guebre-Xabier M,
Girard B
,
Das R,
Corbett-Helaire KS
,
Seder RA,
Graham BS
,
Edwards DK
,
Patel N,
Smith G
,
Ward AB
(2024) bioRxiv
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(2024) bioRxiv
Abstract:
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.
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.