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July 21, 2022PLoS PathogensOpen Access

Structure-selected RBM immunogens prime polyclonal memory responses that neutralize SARS-CoV-2 variants of concern

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Why the study?

The full-length Spike protein is immunogenic, but most antibodies do not target the virus: ACE2 interface, prompting efforts to focus the antibody response to the receptor-binding motif.

Population

C57BL/6 mice

Comparison

Priming with plasmid (p)DNA constructs followed by recombinant Spike protein booster

Design

Preclinical animal study

Key result

Priming mice with plasmid DNA encoding conformationally-constrained RBM immunogens followed by a Spike protein booster induced polyclonal memory responses that neutralized authentic SARS-CoV-2 WA1 and variants of concern.

Authors

GAGonzalo AlmanzaACAlex E. ClarkVKValentina L. Kouznetsova

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Overview

Supports structure-selected RBM immunogens for broad neutralization in mice; leaves open translation to human SARS-CoV-2 vaccines.

Structured PICO

P
Population
16 female C57BL/6 mice immunized with plasmid DNA encoding RBM immunogens followed by a recombinant Spike protein booster to evaluate neutralizing antibody responses.
I
Intervention
Priming with plasmid (p)DNA encoding conformationally-constrained immunogens (RBM amino acid residues inserted into hypervariable loops of an immunoglobulin molecule) followed by booster immunization with recombinant Spike protein
O
Outcome
Antibody binding to purified receptor-binding domain (RBD) and Spike proteins, and neutralization of authentic WA1 virus and variants of concern (B.1.351, B.1.617.2, BA.1)surrogate

Structure-selected RBM immunogens can focus the antibody response to conserved sites, generating neutralizing antibodies across multiple SARS-CoV-2 variants.

Limitations

  • Small sample size (N=4 per group)
  • The dose of Spike protein used in the booster immunization was probably excessive and may have masked the true potential of the memory response
  • Results cannot be extrapolated to predict transmission inhibition in vivo

Cite This Study

Almanza et al. (2022) studied SARS-CoV-2 (n=16). Structure-selected RBM immunogens (pDNA prime) vs. Spike protein boost only was evaluated on Neutralization of authentic SARS-CoV-2 isolates (IC50). Priming mice with plasmid DNA encoding conformationally-constrained RBM immunogens followed by a Spike protein booster induced polyclonal memory responses that neutralized authentic SARS-CoV-2 WA1 and variants of concern.

synapsesocial.com/papers/6aa4b917619ecad50f3d5f0chttps://doi.org/10.1371/journal.ppat.1010686
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