TY - JOUR
T1 - Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability
AU - Brouwer, Philip J.M.
AU - Caniels, Tom G.
AU - van der Straten, Karlijn
AU - Snitselaar, Jonne L.
AU - Aldon, Yoann
AU - Bangaru, Sandhya
AU - Torres, Jonathan L.
AU - Okba, Nisreen M.A.
AU - Claireaux, Mathieu
AU - Kerster, Gius
AU - Bentlage, Arthur E.H.
AU - van Haaren, Marlies M.
AU - Guerra, Denise
AU - Burger, Judith A.
AU - Schermer, Edith E.
AU - Verheul, Kirsten D.
AU - van der Velde, Niels
AU - van der Kooi, Alex
AU - van Schooten, Jelle
AU - van Breemen, Mariëlle J.
AU - Bijl, Tom P.L.
AU - Sliepen, Kwinten
AU - Aartse, Aafke
AU - Derking, Ronald
AU - Bontjer, Ilja
AU - Kootstra, Neeltje A.
AU - Joost Wiersinga, W.
AU - Vidarsson, Gestur
AU - Haagmans, Bart L.
AU - Ward, Andrew B.
AU - de Bree, Godelieve J.
AU - Sanders, Rogier W.
AU - van Gils, Marit J.
PY - 2020/8/7
Y1 - 2020/8/7
N2 - The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3, and VH1-24 gene usage. A subset of the antibodies was able to potently inhibit authentic SARS-CoV-2 infection at a concentration as low as 0.007 micrograms per milliliter. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.
AB - The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3, and VH1-24 gene usage. A subset of the antibodies was able to potently inhibit authentic SARS-CoV-2 infection at a concentration as low as 0.007 micrograms per milliliter. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.
UR - http://www.scopus.com/inward/record.url?scp=85087669111&partnerID=8YFLogxK
U2 - https://doi.org/10.1126/science.abc5902
DO - https://doi.org/10.1126/science.abc5902
M3 - Article
C2 - 32540902
SN - 0036-8075
VL - 369
SP - 643
EP - 650
JO - Science
JF - Science
IS - 6504
ER -