Epitope mapping of neutralising anti‐SARS‐CoV‐2 monoclonal antibodies: Implications for immunotherapy and vaccine design

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the causative agent of the coronavirus disease 2019 (COVID‐19) pandemic. This disease has currently affected more than 346 million people and resulted in more than 5.5 million deaths in many countries. Neutralising monoclonal antibodies (MAbs) against the SARS‐CoV‐2 virus could serve as prophylactic/therapeutic agents in COVID‐19 infection by providing passive protection against the virus in individuals. Until now, no Food and Drug Administration/European Medicines Agency‐approved neutralising MAb against SARS‐CoV‐2 virus exists in the market, though a number of MAbs have been authorised for emergency use. Therefore, there is an urgent need for development of efficient anti‐SARS‐CoV‐2 neutralising MAbs for use in the clinic. Moreover, neutralising anti‐SARS‐CoV‐2 MAbs could be used as beneficial tools for designing epitope‐based vaccines against the virus. Given that the target epitope of a MAb is a crucial feature influencing its neutralising potency, target epitopes of neutralising anti‐SARS‐CoV‐2 MAbs already reported in the literature and reactivity of these MAbs with SARS‐CoV‐2 variants are reviewed herein.

Diagnostic performance of a novel antigen-capture ELISA for the detection of SARS-CoV-2

“…Furthermore, the P13L, Δ31-33, and S413R are exclusive of the Omicron variant among the variants of concern [ 28 , 30 ]. Since NP is highly conserved and is abundantly expressed in SARS-CoV-2 infected-cells, compared with the other structural proteins [ [10] , [11] , [12] ], we established a sandwich ELISA for the detection of NP antigen. Our assay was able to detect as low as 43 pg/ml of NP protein.…”

“…Similar to other coronaviruses, SARS-CoV-2 is an enveloped virus with a single-stranded, positive sense RNA genome. The virus has four structural proteins, including spike (S), nucleocapsid (NP), envelope (E) and membrane (M) [ 9 , 10 ]. Among them, NP is less prone to genetic variations and highly conserved and immunogenic protein with approximately 90% homology in amino acid sequences with SARS-CoV NP [ [11] , [12] , [13] ].…”

SARS‐CoV‐2 neutralising antibody therapies: Recent advances and future challenges

“…The hACE2 protein has been discerned as a critical site of the SARS-CoV-2 spike (S) protein. 10,13 The viral attachment process commences as the S protein interacts with gangliosides, followed by subsequent recognition of heparan sulfate (HS) and hACE2 via the RBD. 14 On top of that, neutralising antibodies can prevent virus-host cell fusion by forming virus-antibody complexes when binding to the viral surface.…”

“…Currently, the emerging immunotherapies primarily encompass interferon-based interventions, antibodyderived treatments, the mitigation of cytokine storms, and the promotion of active immunisation via vaccines. [8][9][10] Among these therapeutic approaches, neutralising antibody therapy holds a prominent position. COVID-19 neutralising antibody therapeutics involves the targeted binding of antibodies to specific cellular receptors, effectively limiting virus adhesion and mitigating the risk of subsequent infection.…”

Novel chimeric proteins mimicking SARS-CoV-2 spike epitopes with broad inhibitory activity

“…Antibody responses produced by SARS-CoV-2 infection are mostly induced against the nucleocapsid protein and the spike protein and, within this, against the S1 subunit [30] , [31] . Neutralizing Ab responses in COVID-19 convalescent patients are mainly directed to the RBD but mutations in emerging SARS-CoV-2 variants drastically reduce their neutralization potential [3] , [32] , [33] .…”