Neutralizing monoclonal antibodies for treatment of COVID-19

Abstract

Several neutralizing monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and are now under evaluation in clinical trials. With the US Food and Drug Administration recently granting emergency use authorizations for neutralizing mAbs in non-hospitalized patients with mild-to-moderate COVID-19, there is an urgent need to discuss the broader potential of these novel therapies and to develop strategies to deploy them effectively in clinical practice, given limited initial availability. Here, we review the precedent for passive immunization and lessons learned from using antibody therapies for viral infections such as respiratory syncytial virus, Ebola virus and SARS-CoV infections. We then focus on the deployment of convalescent plasma and neutralizing mAbs for treatment of SARS-CoV-2. We review specific clinical questions, including the rationale for stratification of patients, potential biomarkers, known risk factors and temporal considerations for optimal clinical use. To answer these questions, there is a need to understand factors such as the kinetics of viral load and its correlation with clinical outcomes, endogenous antibody responses, pharmacokinetic properties of neutralizing mAbs and the potential benefit of combining antibodies to defend against emerging viral variants.

Reduced sensitivity of infectious SARS-CoV-2 variant B.1.617.2 to monoclonal antibodies and sera from convalescent and vaccinated individuals

“…We assessed the sensitivity of B.1.617.2 to a panel of human mAbs using the S-Fuse assay. We tested four clinically approved antibodies, Bamlanivimab (LY-CoV555), Etesevimab (LY-CoV016), Casirivimab (REGN10933) and Imdevimab (REGN10987) targeting the RBD 20,36 as well as four other anti-RBD (RBD-48, RBD-85, RBD-98 and RBD-109) and four anti-NTD (NTD-18, NTD-20, NTD-69 and NTD-71) antibodies that were derived from convalescent individuals (Planchais et al, in preparation). Neutralizing anti-SARS-CoV-2 mAbs targeting the RBD can be classified into 4 main categories depending on their binding epitope 35,37 .…”

Impact of glycosylation on a broad-spectrum vaccine against SARS-CoV-2

“…5f). These results have not only suggested that bivalent m31A7 can stabilize the interaction with S protein, thereby providing high avidity, but also highlighted its high affinity comparable to or higher than many other mAbs identified recently 6,42,43 .…”

“…5f). These results have not only suggested that bivalent m31A7 can stabilize the interaction with S protein, thereby providing high avidity, but also highlighted its high affinity comparable to or higher than many other mAbs identified recently 6,42,43 . Taken together, the monoglycosylated S protein (Smg) vaccine has the potential to induce broadly neutralizing antibodies with high affinities.…”

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Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 167 million confirmed cases and over 3 million deaths so far [1][2][3][4] . This global pandemic has led to great efforts directed toward the study of this virus and its infection mechanism as well as development of effective means to control this devastating infectious disease [5][6][7][8] . Like many other viral surface proteins, the trimeric SARS-CoV-2 spike (S) protein is heavily glycosylated with 22 N-and 2 O-glycosites per monomer which are likely to influence S protein folding and evade host immune response 9 .

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Massively Multiplexed Affinity Characterization of Therapeutic Antibodies Against SARS-CoV-2 Variants

“…A handful of antibody therapies have been granted emergency use authorization by the FDA, over a dozen are in late-stage clinical development, and many more are in preclinical development (17). However, previous efforts to measure the effect of RBD variants on the efficacy of antibody candidates for COVID-19 have mostly been limited to characterizing individual CoV-2 RBD variants on a small number of antibody candidates (8,(18)(19)(20)(21)(22)(23).…”