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 and protection 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 B.1.1.28.1 (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.

Graphical Abstract

Abstract

Antigenic drifts in SARS-CoV-2 variants permit the escape from neutralizing antibody in COVID-19 convalescent plasma. Moriyama et al. reveals the evolution of serological immunity with time that counters SARS-CoV-2 variants via the affinity-maturation and epitope focusing of IgG antibodies that are resistant to the viral escape.