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

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

Administration of plasma from convalescent patients or neutralizing monoclonal antibodies (mAbs) is potent therapeutic option for COVID-19 caused by 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 patients with COVID-19 infected with prototypic SARS-CoV-2 by single cell sorting of 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 to 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.