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

• Published in: Immunity (Cambridge, Mass.) Vol. 54; no. 8; pp. 1841 - 1852.e4
• Main Authors: Moriyama, Saya, Adachi, Yu, Sato, Takashi, Tonouchi, Keisuke, Sun, Lin, Fukushi, Shuetsu, Yamada, Souichi, Kinoshita, Hitomi, Nojima, Kiyoko, Kanno, Takayuki, Tobiume, Minoru, Ishijima, Keita, Kuroda, Yudai, Park, Eun-Sil, Onodera, Taishi, Matsumura, Takayuki, Takano, Tomohiro, Terahara, Kazutaka, Isogawa, Masanori, Nishiyama, Ayae, Kawana-Tachikawa, Ai, Shinkai, Masaharu, Tachikawa, Natsuo, Nakamura, Shigeki, Okai, Takahiro, Okuma, Kazu, Matano, Tetsuro, Fujimoto, Tsuguto, Maeda, Ken, Ohnishi, Makoto, Wakita, Takaji, Suzuki, Tadaki, Takahashi, Yoshimasa
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 10.08.2021; The Author(s). Published by Elsevier Inc
• Subjects: affinity maturation; neutralizing antibody; SARS-CoV-2; SARS-CoV-2 variants of concern; neutralizing antibody; SARS-CoV-2; SARS-CoV-2 variants of concern; affinity maturation
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2021.06.015

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. [Display omitted] •Qualitative changes in plasma neutralizing antibody are longitudinally analyzed•Affinity-matured antibodies with resistance to variants are durably maintained•Neutralizing potency and breadth to SARS-CoV-2 variants increase with time•Serological immunity evolves with time to counter SARS-CoV-2 variants Antigenic drifts in SARS-CoV-2 variants permit escape from neutralizing antibody in COVID-19 convalescent plasma. Moriyama et al. reveal the evolution of serological immunity with time that counters SARS-CoV-2 variants via affinity maturation and durable elicitation of IgG antibodies that are resistant to viral escape.