Cross-Recognition of SARS-CoV-2 B-Cell Epitopes with Other Betacoronavirus Nucleoproteins

Abstract

The B and T lymphocytes of the adaptive immune system are important for the control of most viral infections, including COVID-19. Identification of epitopes recognized by these cells is fundamental for understanding how the immune system detects and removes pathogens, and for antiviral vaccine design. Intriguingly, several cross-reactive T lymphocyte epitopes from SARS-CoV-2 with other betacoronaviruses responsible for the common cold have been identified. In addition, antibodies that cross-recognize the spike protein, but not the nucleoprotein (N protein), from different betacoronavirus have also been reported. Using a consensus of eight bioinformatic methods for predicting B-cell epitopes and the collection of experimentally detected epitopes for SARS-CoV and SARS-CoV-2, we identified four surface-exposed, conserved, and hypothetical antigenic regions that are exclusive of the N protein. These regions were analyzed using ELISA assays with two cohorts: SARS-CoV-2 infected patients and pre-COVID-19 samples. Here we describe four epitopes from SARS-CoV-2 N protein that are recognized by the humoral response from multiple individuals infected with COVID-19, and are conserved in other human coronaviruses. Three of these linear surface-exposed sequences and their peptide homologs in SARS-CoV-2 and HCoV-OC43 were also recognized by antibodies from pre-COVID-19 serum samples, indicating cross-reactivity of antibodies against coronavirus N proteins. Different conserved human coronaviruses (HCoVs) cross-reactive B epitopes against SARS-CoV-2 N protein are detected in a significant fraction of individuals not exposed to this pandemic virus. These results have potential clinical implications.

Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

“…The most likely source of SARS-CoV-2 cross-reactive antibodies are HCoV-specific memory B cells [ 711 ]. The molecular targets are mainly the S [ 704 , 705 , 711 , 712 , 713 ] and N proteins [ 694 , 704 , 705 , 713 , 714 ], but cross-recognition of conserved non-structural proteins [ 704 ] has also been reported. These antibodies recognize SARS and MERS coronaviruses [ 712 ] along with seasonal HCoV antigens [ 694 , 711 , 712 , 714 , 715 , 716 ], indicating broad cross-reactivity.…”

“…The molecular targets are mainly the S [ 704 , 705 , 711 , 712 , 713 ] and N proteins [ 694 , 704 , 705 , 713 , 714 ], but cross-recognition of conserved non-structural proteins [ 704 ] has also been reported. These antibodies recognize SARS and MERS coronaviruses [ 712 ] along with seasonal HCoV antigens [ 694 , 711 , 712 , 714 , 715 , 716 ], indicating broad cross-reactivity. Due to closer relatedness, the probability to cross-react to SARS-CoV-2 might be higher for immune responses that had been elicited against HCoVs belonging to the betacoronaviruses compared to those that targeted earlier alphacoronavirus infections.…”

Mapping of conserved immunodominant epitope peptides in the outer membrane porin (Omp) L of prominent Enterobacteriaceae pathogens associated with gastrointestinal infections

“…The 4 linear B-cell epitopes ENREAYNLASDQ (25aa–36aa), TLQRDDELKHGYNE (60aa–373aa), NHNNYSSTDLNGELDNNDS (127aa–145aa), and LDRNVGPYHREQ (208aa–3219aa) are highly conserved among the other Enterobacteriaceae pathogens with high degree of sequence similarity in B-cell epitopes. Though there are few mutated positions in the amino acid residues of these B-cell epitopes, the higher sequence identity in the B-cell epitopes would vouch for the cross-reactivity as this case was observed in few studies [ 20 , 21 ]. The discontinuous B-cell epitope regions predicted from the highly refined models of OmpL structures are also conserved among the Enterobacteriaceae pathogens.…”

Potential use of endemic human coronaviruses to stimulate immunity against pathogenic SARS-CoV-2 and its variants

“…Importantly, antigenic regions that were found to be immunodominant in a study by Tajuelo et al (59). These included regions for receptor binding and the proteolytic cleavage sites of the S protein, as well as the N-terminal RNA-binding and C-terminal dimerization domains of the N protein, which have been shown to be critical for virus attachment and entry, cell-to-cell fusion, and virus replication [ 37 , 53 , 56–59 ]. The region of the S1 subunit responsible for receptor binding differs considerably among CoV species, which utilize different domains and host cell receptors and consequently differ in their tissue tropism ( Table 1 [ 36 , 39 , 47 , 60 , 62 , 63 ]).…”