Decline of humoral responses against SARS-CoV-2 Spike in convalescent individuals

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>In the absence of effective vaccines and with limited therapeutic options, convalescent plasma is being collected across the globe for potential transfusion to COVID-19 patients. The therapy has been deemed safe and several clinical trials assessing its efficacy are ongoing. While it remains to be formally proven, the presence of neutralizing antibodies is thought to play a positive role in the efficacy of this treatment. Indeed, neutralizing titers of ≥1:160 have been recommended in some convalescent plasma trials for inclusion. Here we performed repeated analyses at one-month interval on 31 convalescent individuals to evaluate how the humoral responses against the SARS-CoV-2 Spike, including neutralization, evolve over time. We observed that receptor-binding domain (RBD)-specific IgG slightly decreased between six and ten weeks after symptoms onset but RBD-specific IgM decreased much more abruptly. Similarly, we observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing SARS-CoV-2 S wild-type or its D614G variant. If neutralization activity proves to be an important factor in the clinical efficacy of convalescent plasma transfer, our results suggest that plasma from convalescent donors should be recovered rapidly after symptoms resolution.</jats:p>

Longitudinal analysis of the humoral response to SARS-CoV-2 spike RBD in convalescent plasma donors

“…However, the most striking observation comes from the comparison of the 3 rd and 4 th quartile (70 to 84 and 85 to 114 days after symptoms onset, respectively), where a marked decrease in the mean OD values (significative mean OD decrease of -0.486 from 1.321 ± 0.720 to 0.835 ± 0.670, representing a 36.8% decrease with p-value of 0.0052) and an even more pronounced decrease in median values (median OD decreases from 1.411 (IQR 1.52) to 0.411 (IQR 1.15) representing a 70.1% decrease) were observed. Altogether, these observations are in agreement with recent studies reporting a decrease in anti-RBD responses and neutralization activity in the plasma of convalescent donors a few weeks after symptoms resolution (19)(20)(21)(22) Interestingly, the decrease in mean and median OD values during a period of about 20 days (considering the mean and median of 3 rd and 4 th quartiles, both of 76 and 95 days respectively) is reminiscent of the plasma IgG half-life of 21 days (23), suggesting that de novo synthesis of anti-RBD antibodies stopped between the 3 rd and 4 th quartiles in all CCP donors. This time frame is consistent with the first wave of a humoral immune response during which short-lived plasma cells actively secrete pathogen-specific antibodies until the antigen is eliminated (24).…”

“…The presence of antibodies against SARS-CoV-2 RBD was determined using a semi-quantitative ELISA. The assay was adapted from a recently described protocol (20,21). The plasmid encoding for SARS-CoV-2 S RBD was synthesized commercially (Genscript).…”

Interaction of human ACE2 to membrane-bound SARS-CoV-1 and SARS-CoV-2 S glycoproteins

“…Both the SARS-CoV-2 S and its D614G counterpart demonstrated a positive cooperativity of sACE2 binding (Hill coefficient > 1) ( Figure 1A). Thus, indicating that the D614G mutation does not overly affect S conformation, at least regarding sACE2 interaction, in line with recent findings [26,27]. Interestingly, SARS-CoV-1 S presented negative cooperativity (Hill coefficient < 1), suggesting that the interaction of sACE2 with one SARS-CoV-1 S protomer reduces the efficiency with which additional sACE2 molecules can engage adjacent S protomers.…”

Antibody binding to SARS-CoV-2 S glycoprotein correlates with, but does not predict neutralization

“…Several reports described a significant decrease in the neutralization capacity of plasma from convalescent individuals starting six weeks after symptoms onset [13,14,25,26]. To evaluate whether this was related to the capacity of plasma to capture viral particles, we analyzed the neutralization and viral capture capacity of serological samples obtained from fifteen convalescent donors at six and ten weeks after symptoms onset.…”

“…The transfer of convalescent plasma to COVID-19 patients was shown to be well tolerated and presented some positive signs [6][7][8][9][10]. Similarly, some antibodies targeting the Spike (S) glycoprotein from SARS-CoV-2, isolated from virus infected individuals, were shown to potently neutralize viral and pseudoviral particles carrying the S glycoprotein of the virus [11][12][13][14][15][16] and in some instances protected small animals from SARS-CoV-2 infection [17,18].…”