Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients

Cell
Christoph KreerFlorian Klein

Abstract

The SARS-CoV-2 pandemic has unprecedented implications for public health, social life, and the world economy. Because approved drugs and vaccines are limited or not available, new options for COVID-19 treatment and prevention are in high demand. To identify SARS-CoV-2-neutralizing antibodies, we analyzed the antibody response of 12 COVID-19 patients from 8 to 69 days after diagnosis. By screening 4,313 SARS-CoV-2-reactive B cells, we isolated 255 antibodies from different time points as early as 8 days after diagnosis. Of these, 28 potently neutralized authentic SARS-CoV-2 with IC100 as low as 0.04 μg/mL, showing a broad spectrum of variable (V) genes and low levels of somatic mutations. Interestingly, potential precursor sequences were identified in naive B cell repertoires from 48 healthy individuals who were sampled before the COVID-19 pandemic. Our results demonstrate that SARS-CoV-2-neutralizing antibodies are readily generated from a diverse pool of precursors, fostering hope for rapid induction of a protective immune response upon vaccination.

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Datasets Mentioned

BETA
MT658806
MT658861
MN908947
KJ660347
M93258

Methods Mentioned

BETA
phage display
PCR
ELISA
blood draws
Blood draw
transfection
electrophoresis
ELISAs
size exclusion chromatography
chip

Software Mentioned

IgBLAST
R
Clustal Omega
GraphPad Prism
Python
Prism
raxmlGUI
pRESTO
RAxML
Excel

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