6.2  Anti-SARS-CoV-2 specific antibodies
Up to this moment, only few tests of specific Abs against SARS-CoV-2 have been reported. 311mab-31B5 and 311mab-32D4 human monoclonal Abs could strongly and specifically bind the RBD protein. These mAbs could efficiently block SARS-CoV-2-ACE2 interaction and neutralize pseudovirus entry into host cells ectopically expressing ACE2 [105].
Peptides S14P5 and S21P2 in the two distinct peptide pools S14 and S21 from SARS-CoV-2 S library were strongly detected in COVID-19 patients but not in SARS-CoV patients by using pools of overlapping linear peptides and functional assays [78]. With the data from antibodies depletion assays, researchers indicated that S14P5 and S21P2 were necessary for SARS-CoV-2 neutralization. Moreover, pool S51 contains very conserved fusion peptide in coronavirus [106,107] and is partially overlapped in the sera of SARS-CoV and SARS-CoV-2 patients. These results suggested that S51 may be a potential pan-coronavirus epitope. Sera from recalled SARS-CoV patients could neutralize SARS-CoV, but not the SARS-CoV-2 pseudotyped lentiviruses [78].
In an effort to screen a set of B cell and T cell epitopes of SARS-CoV toward to the spike S and nucleocapsid (N) proteins of SARS-CoV-2, 27 epitope-sequences were identical within SARS-CoV-2 proteins among 115 T cell epitopes. However, 19 out of 27 epitopes are associated with five distinct MHC alleles (at 4-digit resolution): HLA-A*02:01, HLA-B*40:01, HLA-DRA*01:01, HLA-DRB1*07:01, and HLA-DRB1*04:01. For B cell epitopes, they found 49 identical match epitope-sequences that have potential for developing effective vaccines to combat the SARS-CoV-2 [108]. Based on the sequence of the spike glycoprotein, seven epitope residue/regions (491–505, 558–562, 703–704, 793–794, 810, 914, and 1140–1146) in the surface glycoprotein were predicted to be associated with a robust immune response to SARS-CoV-2 [30]. Other candidate epitopes need to be confirmed [95,108].
Using the memory B cells from a survivor who was SARS-CoV infected in 2003, one nAb anti-RBD named S309 was found to bind to SARS-CoV-2 without interfering ACE2 binding. Besides, S309 could recognize a N343-glycan epitope that is distant from the RBM of SARS-CoV-2. Interestingly, N343-glycan of SARS-CoV-2 corresponds to SARS-CoV N330 and they are highly conserved. S309 potently neutralized both pseudotyped SARS-CoV and SARS-CoV-2 and also the authentic SARS-CoV-2 [109].
Using machine learning approaches with the data from other virus outbreaks, some synthetic nAbs named C3, C7, C14, C17, C18, Co1, Co2 and Co4 showed a potential to against SARS-CoV-2. The authors also confirmed that the mutations of Methionine and Tyrosine could increase the affinity of antibody-target binding [110].
19 potential immunogenicity B-cell epitopes, including 2 epitopes located within the RBD region were reported using in silico analysis. 17 of them have >14 amino acids. The B-cell epitopes which had highest score in this study is the 1052-FPQSAPH-1058 located at position 1052aa of S protein. 499 T-cell epitopes bound 34 most popular HLA alleles in the Chinese population were also found. Around 30 candidate vaccine peptides in which 5 peptides located within the RBD region and 17 of them contained both B- and T-cell epitopes, were designed [111]. These vaccine candidates are theoretically able to induce either specific humoral or cellular immune against SARS-CoV-2.
A panel of five humanized single domain antibodies (sdAbs) or nanobodies, 1E2, 2F2, 3F11, 4D8 and 5F8, was recently discovered. These sdAbs bound SARS-CoV-2 tightly but not SARS-CoV, except for 5F8 could bind both viruses but with weaker affinity to SARS-CoV. They also showed neutralization activity against both pseudotyped and authentic SARS-CoV-2. 1E2, 3F11 and 4D8 completely prevented SARS-CoV-2 RBD-ACE2 binding but this effect of 2F2 and 5F8 was only partial. Interestingly, the fusion of the human IgG1 Fc to these sdAbs improved their neutralization activity by 10- to 80-fold [112].
Due to the lack of repairing mechanism of RNA virus replicase complex, SARS-CoV-2 mutations frequently occur during viral replication [111]. The genetic drifts of SARS-CoV-2 are a selective evolution toward less immunogenicity for host immune surveillance by T- or B-cells. The latter appearing strains are less immunogenic than earlier ones [113]. Antigenic drift is also reported in the COVID-19 pandemic. The highly prevalent 23403A > G (p.D614G) variant in the European population may result in vaccine mismatches with little protection to that group of patients [114,115].
Though SARS-COV-2 genome has a much lower mutation rate and genetic diversity than SARS, some of its mutations attract the special attention of scientists. Single amino acid mutation R408I in RBD can reduce the affinity of ACE2 receptor binding [115] that leads to a low or ineffective vaccine for the future epidemic. Effectively, sequence alignment showed that this 408R is strictly conserved in SARS-CoV-2, SARS-CoV. 408R located at the interface between RBD and ACE2, but positioned relatively far away from ACE2, does not have direct interaction with ACE2. 408R can form a hydrogen bond with the 90 N of ACE2. This hydrogen bond is suggested to contribute to the high binding affinity of ACE2 binding [115].