Abstract
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have become a major concern in the containment of current pandemic. The variants, including B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta) have shown reduced sensitivity to monoclonal antibodies, plasma and/or sera obtained from convalescent patients and vaccinated individuals. Development of potent therapeutic monoclonal antibodies (mAbs) with broad neutralizing breadth have become a priority for alleviating the devastating effects of this pandemic. Here, we review some of the most promising broadly neutralizing antibodies obtained from plasma of patients that recovered from early variants of SARS-CoV-2 that may be effective against emerging new variants of the virus. This review summarizes several mAbs, that have been discovered to cross-neutralize across Sarbecoviruses and SARS-CoV-2 escape mutants. Understanding the characteristics that confer this broad and cross-neutralization functions of these mAbs would inform on the development of therapeutic antibodies and guide the discovery of second-generation vaccines.
Highlights
Analysis of the breadth and potency of neutralizing antibodies elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vital for understanding the quality of immune protection and unraveling optimal targets for therapeutic or vaccine design [1]
SARS-CoV-2 variants escape neutralization by antibodies from vaccine and natural infection, which highlight the urgent need for a wide range of potently neutralizing antibodies against variants [42, 44, 47, 87]
The ability of SARS-CoV-2 variants to negatively alter the trajectory of the pandemic highlight the urgent need for antibody therapies that can be developed in real time to counter the virus as it evolves
Summary
Analysis of the breadth and potency of neutralizing antibodies (nAbs) elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vital for understanding the quality of immune protection and unraveling optimal targets for therapeutic or vaccine design [1]. The majority of the more potent neutralizing monoclonal antibodies (mAbs) characterized to date bind the RBD of the viral spike protein [5,6,7,8,9,10,11], though some mAbs against the NTD have been described [12, 13] Antibodies bind their epitopes using diversified loops, termed complementarity-determining regions (CDRs) rearranged within the variable regions of heavy (VH) and light (VL) chains of the immunoglobulin molecules (Figure 2). As the levels of herd immunity increase through natural and vaccine induced immunity it is reasonable to speculate that this will provide greater selection pressure on the virus and we may see more mutants continue to emerge Due to their potential to transform the strength and kinetics of the binding with ACE2, mutations that arise in the RBD are of particular interest. The Delta variant, B.1.617.2, has become the dominant SARS-COV-2
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