Monoclonal antibody therapies in the management of SARS-CoV-2 infection

Abstract

Introduction: Neutralizing antibodies (NAbs) that target key domains of the spike protein in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have therapeutic value because of their specificity. Depending on the targeted epitope, single agents may be effective, but combined treatment involving multiple NAbs may be necessary to prevent the emergence of resistant variants.

Areas covered: This article highlights the accelerated regulatory processes established to facilitate the review and approval of potential therapies. An overview of treatment approaches for SARS-CoV-2 infection, with detailed examination of the preclinical and clinical evidence supporting the use of NAbs, is provided. Finally, insights are offered into the potential benefits and challenges associated with the use of these agents.

Expert opinion: NAbs offer an effective, evidence-based therapeutic intervention during the early stages of SARS-CoV-2 infection when viral replication is the primary factor driving disease progression. As the pandemic progresses, appropriate use of NAbs will be important to minimize the risk of escape variants. Ultimately, the availability of effective treatments for COVID-19 will allow the establishment of treatment algorithms for minimizing the substantial rates of hospitalization, morbidity (including long COVID) and mortality currently associated with the disease.

Keywords: Bamlanivimab and etesevimab; COVID-19; SARS-CoV-2; casirivimab and imdevimab; neutralizing antibodies; regdanvimab; sotrovimab.

Figure 1.

Regulatory pathways adopted by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) during the COVID-19 pandemic. COVID-19, coronavirus disease 2019; COVID-ETF: COVID-19 EMA pandemic Task Force; CTAP: Coronavirus Treatment Acceleration Program; EUA: Emergency Use Authorization; IND: investigational new drug; RCT: randomized controlled trial.

Figure 2.

Mechanism of action of anti-receptor-binding domain (RBD) SARS-CoV-2 neutralizing antibodies (NAbs). (a) SARS-CoV-2 infection occurs via binding of the RBD to the angiotensin-converting enzyme 2 (ACE2) receptor on host cells; (b) NAb interferes with binding of the RBD/spike (S) protein to the ACE2 receptor, blocking virus entry into host cells. Fab: fragment antigen binding; Fc: fragment crystallizable.

Figure 3.

SARS-CoV-2 spike protein structure, conformation and targets of receptor-binding domain (RBD)-dependent neutralizing antibodies (NAbs). (a) Different conformations of spike protein. (b) Representation of four classes of SARS-CoV-2 RBD-dependent NAbs. Figure reproduced with modification from Kumar S, Chandele A, Sharma A. Current status of therapeutic monoclonal antibodies against SARS-CoV-2. PLoS Pathog. 2021;17(9):e1009885 [58] under CC-BY license.