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Temporal maturation of neutralizing antibodies in COVID-19 convalescent individuals improves potency and breadth to circulating SARS-CoV-2 variants.

Abstract
Antibody titers against SARS-CoV-2 slowly wane over time. Here, we examined how time affects antibody potency. To assess the impact of antibody maturation on durable neutralizing activity against original SARS-CoV-2 and emerging variants of concern (VOCs), we analyzed receptor binding domain (RBD)-specific IgG antibodies in convalescent plasma taken 1-10 months after SARS-CoV-2 infection. Longitudinal evaluation of total RBD IgG and neutralizing antibody revealed declining total antibody titers but improved neutralization potency per antibody to original SARS-CoV-2, indicative of antibody response maturation. Neutralization assays with authentic viruses revealed that early antibodies capable of neutralizing original SARS-CoV-2 had limited reactivity toward B.1.351 (501Y.V2) and P.1 (501Y.V3) variants. Antibodies from late convalescents exhibited increased neutralization potency to VOCs, suggesting persistence of cross-neutralizing antibodies in plasma. Thus, maturation of the antibody response to SARS-CoV-2 potentiates cross-neutralizing ability to circulating variants, suggesting that declining antibody titers may not be indicative of declining protection.
AuthorsSaya Moriyama, Yu Adachi, Takashi Sato, Keisuke Tonouchi, Lin Sun, Shuetsu Fukushi, Souichi Yamada, Hitomi Kinoshita, Kiyoko Nojima, Takayuki Kanno, Minoru Tobiume, Keita Ishijima, Yudai Kuroda, Eun-Sil Park, Taishi Onodera, Takayuki Matsumura, Tomohiro Takano, Kazutaka Terahara, Masanori Isogawa, Ayae Nishiyama, Ai Kawana-Tachikawa, Masaharu Shinkai, Natsuo Tachikawa, Shigeki Nakamura, Takahiro Okai, Kazu Okuma, Tetsuro Matano, Tsuguto Fujimoto, Ken Maeda, Makoto Ohnishi, Takaji Wakita, Tadaki Suzuki, Yoshimasa Takahashi
JournalImmunity (Immunity) Vol. 54 Issue 8 Pg. 1841-1852.e4 (08 10 2021) ISSN: 1097-4180 [Electronic] United States
PMID34246326 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin G
Topics
  • Antibodies, Monoclonal (immunology)
  • Antibodies, Neutralizing (immunology)
  • Antibodies, Viral (immunology)
  • Antibody Specificity
  • COVID-19 (epidemiology, immunology, virology)
  • Humans
  • Immunoglobulin G
  • Neutralization Tests
  • SARS-CoV-2 (genetics, immunology)
  • Viral Load

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