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mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants.

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TLDR
This paper reported on the antibody and memory B-cell responses of a cohort of 20 volunteers who received the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccine against SARS-CoV-2.
Abstract
Here we report on the antibody and memory B cell responses of a cohort of 20 volunteers who received the Moderna (mRNA-1273) or Pfizer–BioNTech (BNT162b2) vaccine against SARS-CoV-21–4 Eight weeks after the second injection of vaccine, volunteers showed high levels of IgM and IgG anti-SARS-CoV-2 spike protein (S) and receptor-binding-domain (RBD) binding titre Moreover, the plasma neutralizing activity and relative numbers of RBD-specific memory B cells of vaccinated volunteers were equivalent to those of individuals who had recovered from natural infection5,6 However, activity against SARS-CoV-2 variants that encode E484K-, N501Y- or K417N/E484K/N501-mutant S was reduced by a small—but significant—margin The monoclonal antibodies elicited by the vaccines potently neutralize SARS-CoV-2, and target a number of different RBD epitopes in common with monoclonal antibodies isolated from infected donors5–8 However, neutralization by 14 of the 17 most-potent monoclonal antibodies that we tested was reduced or abolished by the K417N, E484K or N501Y mutation Notably, these mutations were selected when we cultured recombinant vesicular stomatitis virus expressing SARS-CoV-2 S in the presence of the monoclonal antibodies elicited by the vaccines Together, these results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid a potential loss of clinical efficacy The Moderna (mRNA-1273) and Pfizer–BioNTech (BNT162b2) vaccines elicit anti-RBD antibodies similar to those elicited through natural infection with SARS-CoV-2, but their potent neutralizing activity was reduced or abolished by new viral variants of concern

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Journal ArticleDOI

Effects of Spike Mutations in SARS-CoV-2 Variants of Concern on Human or Animal ACE2-Mediated Virus Entry and Neutralization

TL;DR: Important insights are revealed into the host range of SARS-CoV-2 and the effect of recently emergent S protein substitutions on viral entry, virus replication, and antibody-mediated viral neutralization.
Posted ContentDOI

High genetic barrier to escape from human polyclonal SARS-CoV-2 neutralizing antibodies

TL;DR: In this paper, the number and variability of the neutralizing epitopes targeted by polyclonal antibodies in SARS-CoV-2 convalescent and vaccinated individuals are key determinants of neutralization breadth and, consequently, the genetic barrier to viral escape.
References
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Journal ArticleDOI

Features and development of Coot.

TL;DR: Coot is a molecular-graphics program designed to assist in the building of protein and other macromolecular models and the current state of development and available features are presented.
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A simple method for displaying the hydropathic character of a protein

TL;DR: A computer program that progressively evaluates the hydrophilicity and hydrophobicity of a protein along its amino acid sequence has been devised and its simplicity and its graphic nature make it a very useful tool for the evaluation of protein structures.
Journal ArticleDOI

cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination

TL;DR: It is shown that stochastic gradient descent (SGD) and branch-and-bound maximum likelihood optimization algorithms permit the major steps in cryo-EM structure determination to be performed in hours or minutes on an inexpensive desktop computer.
Journal ArticleDOI

Automated electron microscope tomography using robust prediction of specimen movements.

TL;DR: A new method was developed to acquire images automatically at a series of specimen tilts, as required for tomographic reconstruction, using changes in specimen position at previous tilt angles to predict the position at the current tilt angle.
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