Longitudinal analysis of humoral immunity against SARS-CoV-2 Spike in convalescent individuals up to 8 months post-symptom onset

Abstract

Functional and lasting immune responses to the novel coronavirus (SARS-CoV-2) are currently under intense investigation as antibody titers in plasma have been shown to decline during convalescence. Since the absence of antibodies does not equate to absence of immune memory, we sought to determine the presence of SARS-CoV-2-specific memory B cells in COVID-19 convalescent patients. In this study, we report on the evolution of the overall humoral immune responses on 101 blood samples obtained from 32 COVID-19 convalescent patients between 16 and 233 days post-symptom onset. Our observations indicate that anti-Spike and anti-RBD IgM in plasma decay rapidly, whereas the reduction of IgG is less prominent. Neutralizing activity in convalescent plasma declines rapidly compared to Fc-effector functions. Concomitantly, the frequencies of RBD-specific IgM+ B cells wane significantly when compared to RBD-specific IgG+ B cells, which increase over time, and the number of IgG+ memory B cells which remain stable thereafter for up to 8 months after symptoms onset. With the recent approval of highly effective vaccines for COVID-19, data on the persistence of immune responses are of central importance. Even though overall circulating SARS-CoV-2 Spike-specific antibodies contract over time during convalescence, we demonstrate that RBD-specific B cells increase and persist up to 8 months post symptom onset. We also observe modest increases in RBD-specific IgG+ memory B cells and importantly, detectable IgG and sustained Fc-effector activity in plasma over the 8-month period. Our results add to the current understanding of immune memory following SARS-CoV-2 infection, which is critical for the prevention of secondary infections, vaccine efficacy and herd immunity against COVID-19.

A single BNT162b2 mRNA dose elicits antibodies with Fc-mediated effector functions and boost pre-existing humoral and T cell responses

“…To evaluate if vaccine responses were limited to RBD or could be extended to antibodies against the full Spike glycoprotein, we used a cell-based ELISA (CBE) assay to measure levels of antibodies recognizing the native full-length S glycoprotein expressed at the cell surface 47 . In SARS-CoV-2 naïve individuals, the pattern was similar to that observed for the anti-RBD specific response, with a level of total Spike-specific immunoglobulins similar to that observed in previously-infected individuals before vaccination (Figure 1E).…”

“…PBMCs from healthy individuals were used as effector cells. ADCC activity was measured by the loss of Spike-expressing GFP+ target cells, as we reported 47 . In agreement with the lack of Spike-specific antibodies, SARS-CoV-2 naïve individuals did not have detectable ADCC activity prior to vaccination (Figure 3B).…”

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

“…In this model, the ADCC activity of convalescent plasma decreased only modestly compared to the more pronounced decrease in neutralization activity. Substantial ADCC activity was maintained in 85% of donors' plasma up to eight months post symptom onset and strongly correlated with plasma IgG responses [201]. Notably, three weeks post-vaccination with an mRNA vaccine, a time point at which vaccine efficacy is estimated to be >90%, nAb responses are still mostly absent, but anti-SARS-CoV-2 ADCC responses well-developed [200].…”

“…The early anti-SARS-CoV-2 binding and neutralizing Ab response is dominated by IgM, which wanes rapidly. IgA and IgG peak subsequently, and IgG-mediated neutralizing responses are most durable and persist over months, mirrored by neutralization half-lives of a few months in serum but up to >8 months in purified IgG samples [201][202][203][204]. The persisting Ab response can be attributed to a maturing humoral immunity driven by a sustained SARS-CoV-2 antigenic stimulation in the gut of COVID-19 patients [205].…”

Standardization of a flow cytometry SARS-CoV-2 serologic test

“…Intensive work has been done since the beginning of the pandemic to develop reliable, sensitive and specific immunosorbent assays to characterize the humoral response of humans to the virus. The seropositivity determination allows for seroprevalence studies 3 , for the characterization of plasma in the development of convalescent plasma therapy 4 and could be used for the study of the overall antibody responses over time 5,6 , which include vaccine response persistence in due time.…”