Extremely potent human monoclonal antibodies from convalescent Covid-19 patients

Abstract

SUMMARYHuman monoclonal antibodies are safe, preventive and therapeutic tools, that can be rapidly developed to help restore the massive health and economic disruption caused by the Covid-19 pandemic. By single cell sorting 4277 SARS-CoV-2 spike protein specific memory B cells from 14 Covid-19 survivors, 453 neutralizing antibodies were identified and 220 of them were expressed as IgG. Up to 65,9% of monoclonals neutralized the wild type virus at a concentration of >500 ng/mL, 23,6% neutralized the virus in the range of 100 - 500 ng/mL and 9,1% had a neutralization potency in the range of 10 - 100 ng/mL. Only 1,4% neutralized the authentic virus with a potency of 1-10 ng/mL. We found that the most potent neutralizing antibodies are extremely rare and recognize the RBD, followed in potency by antibodies that recognize the S1 domain, the S-protein trimeric structure and the S2 subunit. The three most potent monoclonal antibodies identified were able to neutralize the wild type and D614G mutant viruses with less than 10 ng/mL and are good candidates for the development of prophylactic and therapeutic tools against SARS-CoV-2.One Sentence SummaryExtremely potent neutralizing human monoclonal antibodies isolated from Covid-19 convalescent patients for prophylactic and therapeutic interventions.

Impact of the B.1.1.7 variant on neutralizing monoclonal antibodies recognizing diverse epitopes on SARS-CoV-2 Spike

“…RBD-specific mAb P008_108 is amongst the most potent anti-SARS-CoV-2 mAbs described so far with an IC 50 of 2.3 ng/mL against infectious virus (Andreano et al, 2020a). Although IC 50 values measured against pseudovirus correlated well with those measured against infectious virus ( r = 0.7694, p < 0.0001, Supplemental Figure S3A ), IC 50 values were typically 5-10 fold less potent against infectious virus as seen previously with patient sera (Seow et al, 2020).…”

Functional importance of the D614G mutation in the SARS-CoV-2 spike protein

“…Experimental data pertaining to neutralization of S(G614) and S(D614) pseudoviruses have been reported in abundance. The majority of experiments demonstrate similar neutralization of both S(D614) and S(G614) PVs by antibodies or patient antisera directed against one or the other S protein variant [ 28 , 35 , 51 , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] ], while in some cases S(G614) exhibited greater susceptibility to neutralization [ 51 , 57 ]. Similar neutralization or greater susceptibility of the S(G614) variant have been reproduced with live SARS-CoV-2 as well [ 47 , 48 ].…”

Vaccination boosts protective responses and counters SARS-CoV-2-induced pathogenic memory B cells

“…However, establishing correlations between RBD-specific IgG levels and plasma neutralizing activity only provides indirect evidence of a link between the two parameters. Moreover, demonstrating that RBD is a target of neutralizing antibodies (19)(20)(21)(22) does not directly address the relative contribution of RBD-specific antibodies to the overall plasma neutralizing activity. To directly test the link between RBD specificity and the antibodymediated ability of plasma to neutralize the virus, we depleted RBD-specific antibodies from seropositive plasma samples, and, as a comparator, we also depleted viral Nucleocapsid (N)-specific antibodies, and then tested the effects on neutralizing activity.…”