Resistance of SARS-CoV-2 variants to neutralization by antibodies induced in convalescent patients with COVID-19

Yu Kaku; Takeo Kuwata; Hasan Md Zahid; Takao Hashiguchi; Takeshi Noda; Noriko Kuramoto; Shashwata Biswas; Kaho Matsumoto; Mikiko Shimizu; Yoko Kawanami; Kazuya Shimura; Chiho Onishi; Yukiko Muramoto; Tateki Suzuki; Jiei Sasaki; Yoji Nagasaki; Rumi Minami; Chihiro Motozono; Mako Toyoda; Hiroshi Takahashi; Hiroto Kishi; Kazuhiko Fujii; Tsuneyuki Tatsuke; Terumasa Ikeda; Yosuke Maeda; Takamasa Ueno; Yoshio Koyanagi; Hajime Iwagoe; Shuzo Matsushita

doi:10.1016/j.celrep.2021.109385

Resistance of SARS-CoV-2 variants to neutralization by antibodies induced in convalescent patients with COVID-19

Cell Rep. 2021 Jul 13;36(2):109385. doi: 10.1016/j.celrep.2021.109385. Epub 2021 Jun 25.

Authors

Yu Kaku¹, Takeo Kuwata², Hasan Md Zahid¹, Takao Hashiguchi³, Takeshi Noda⁴, Noriko Kuramoto¹, Shashwata Biswas¹, Kaho Matsumoto¹, Mikiko Shimizu¹, Yoko Kawanami¹, Kazuya Shimura⁵, Chiho Onishi⁵, Yukiko Muramoto⁶, Tateki Suzuki⁷, Jiei Sasaki⁷, Yoji Nagasaki⁸, Rumi Minami⁹, Chihiro Motozono¹⁰, Mako Toyoda¹⁰, Hiroshi Takahashi¹¹, Hiroto Kishi¹¹, Kazuhiko Fujii¹¹, Tsuneyuki Tatsuke¹², Terumasa Ikeda¹³, Yosuke Maeda¹⁴, Takamasa Ueno¹⁰, Yoshio Koyanagi⁵, Hajime Iwagoe¹⁵, Shuzo Matsushita¹⁶

Affiliations

¹ Division of Clinical Retrovirology, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto 860-0811, Japan.
² Division of Clinical Retrovirology, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto 860-0811, Japan. Electronic address: tkuwata@kumamoto-u.ac.jp.
³ Labolatory of Medical Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan; Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
⁴ Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan; CREST, Japan Science and Technology Agency, Kawaguchi, Japan.
⁵ Laboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
⁶ Laboratory of Ultrastructural Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
⁷ Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
⁸ Division of Infectious Diseases, Clinical Research Institute, National Hospitalization Organization, Kyushu Medical Center, Fukuoka, Japan.
⁹ Internal Medicine, Clinical Research Institute, National Hospital Organization, Kyushu Medical Center, Fukuoka, Japan.
¹⁰ Division of Infection and immunity, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto 860-0811, Japan.
¹¹ Department of Respiratory Medicine, Kumamoto City Hospital, Kumamoto 862-8505, Japan.
¹² Faculty of Advanced Science and Technology, Kumamoto University, Kumamoto 860-8555, Japan.
¹³ Division of Molecular Virology and Genetics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto 860-0811, Japan.
¹⁴ Department of Microbiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
¹⁵ Department of Infectious Disease, Kumamoto City Hospital, Kumamoto 862-8505, Japan.
¹⁶ Division of Clinical Retrovirology, Joint Research Center for Human Retrovirus infection, Kumamoto University, Kumamoto 860-0811, Japan. Electronic address: shuzo@kumamoto-u.ac.jp.

Abstract

Administration of convalescent plasma or neutralizing monoclonal antibodies (mAbs) is a potent therapeutic option for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, SARS-CoV-2 variants with mutations in the spike protein have emerged in many countries. To evaluate the efficacy of neutralizing antibodies induced in convalescent patients against emerging variants, we isolate anti-spike mAbs from two convalescent COVID-19 patients infected with prototypic SARS-CoV-2 by single-cell sorting of immunoglobulin-G-positive (IgG⁺) memory B cells. Anti-spike antibody induction is robust in these patients, and five mAbs have potent neutralizing activities. The efficacy of most neutralizing mAbs and convalescent plasma samples is maintained against B.1.1.7 and mink cluster 5 variants but is significantly decreased against variants B.1.351 from South Africa and P.1 from Brazil. However, mAbs with a high affinity for the receptor-binding domain remain effective against these neutralization-resistant variants. Rapid spread of these variants significantly impacts antibody-based therapies and vaccine strategies against SARS-CoV-2.

Keywords: COVID-19; SARS-CoV-2; mAb; neutralizing antibody; variant.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal / immunology
Antibodies, Neutralizing / immunology*
Antibodies, Neutralizing / isolation & purification
Antibodies, Viral / immunology
COVID-19 / immunology*
COVID-19 / therapy*
COVID-19 / virology
COVID-19 Serotherapy
Cell Line
HEK293 Cells
Humans
Immunization, Passive
Male
Mutation
Neutralization Tests
Protein Domains
SARS-CoV-2 / immunology*
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / immunology*

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2