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

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

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.