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.
Highlights
The novel coronavirus, SARS-CoV-2, first described in Wuhan, China, in December 2019, triggers multiple arms of acquired immunity, such as virus-binding antibodies, B cells, CD4+ T cells, and CD8+ T cells (Rydyznski Moderbacher et al, 2020)
COVID-19 convalescent individuals mount durable, albeit declining, neutralizing antibody titers against ancestral SARS-CoV-2 receptor binding domain (RBD) We collected 368 plasma samples between June 2020 and February 2021 from 188 PCR-confirmed COVID-19 patients who suffered from symptomatic infection and were seroconverted by anti-nucleocapsid antibodies
Mild cases were associated with signs and symptoms of COVID-19 without pneumonia, whereas moderate and severe cases were associated with pneumonia without and with the need for supplemental oxygen, respectively
Summary
The novel coronavirus, SARS-CoV-2, first described in Wuhan, China, in December 2019, triggers multiple arms of acquired immunity, such as virus-binding antibodies, B cells, CD4+ T cells, and CD8+ T cells (Rydyznski Moderbacher et al, 2020). RBD epitopes are further divided into at least four classes on the basis of the structure of the antigen-antibody complex (Barnes et al, 2020; Yuan et al, 2021) Among these epitopes, class 1 and 2 epitopes overlap with angiotensin-converting enzyme 2 (ACE2)-binding sites (receptor binding site) and are targeted by potent neutralizing antibodies (Barnes et al, 2020). Similar to other viral antigens, the receptor binding site epitopes on SARS-CoV-2 spike protein are functionally plastic (Greaney et al, 2021; Piccoli et al, 2020) and are highly susceptible to mutations
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