The emergence of SARS-CoV-2 variants threatens to decrease the efficacy of neutralizing antibodies and vaccines

Abstract

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the coronavirus disease (COVID-19) pandemic. As of August 2021, more than 200 million people have been infected with the virus and 4.3 million have lost their lives. Various monoclonal antibodies of human origin that neutralize the SARS-CoV-2 infection have been isolated from convalescent patients for therapeutic and prophylactic purposes. Several vaccines have been developed to restrict the spread of the virus and have been rapidly administered. However, the rollout of vaccines has coincided with the spread of variants of concern. Emerging variants of SARS-CoV-2 present new challenges for therapeutic antibodies and threaten the efficacy of current vaccines. Here, we review the problems faced by neutralizing antibodies and vaccines in the midst of the increasing spread of mutant viruses.

Keywords: SARS-CoV-2; antibodies; variant.

Figure 1.. Generation of monoclonal antibodies.

(A) The traditional hybridoma technology provides a reliable source of mouse monoclonal antibodies. The fusion of a B lymphocyte from an immunized mouse and an immortalized myeloma cell results in a hybridoma secreting monoclonal antibodies, potentiating natural cognate antibody pairing information compared with that obtained using recombinant antibodies. Mouse antibodies, if not humanized, are not suitable for clinical applications due to their immunogenicity. (B) Technology for the production of human recombinant antibodies. Spike-specific B cells from convalescent patients are single-cell sorted using flow cytometry, followed by determination of the antibody variable genes. The genes are cloned into human IgG expression vectors and expressed in mammalian cells such as HEK293T cells. Figures generated with BioRender (https://biorender.com/).

Figure 2.. Variants of concern escape from antibodies in clinical use.

(A) Amino acid substitutions in variants of concern (VOCs) mapped on spike protein [71]. (B) Cryo-EM structures of the spike protein (Protein Data Bank: 7DDN). Two orthogonal views, from the side and top, of the atomic model of the partially open spike trimer [93]. Blue and purple domains indicate the NTD and RBD (open), respectively. (C) Efficacy of neutralizing antibodies in clinical use against VOCs. This table summarizes the sensitivity of each monoclonal antibody to VOCs, but in practice, neutralizing antibodies are used in combination as a cocktail.