3.5. Conserved Protein Sequences Matching Other Coronavirus Family Member and Identification of Pan-Coronavirus Sequences
In addition to variable positions, we also evaluated the presence of protein regions conserved among coronavirus species, as these may support the design of immunogen sequences for pan-coronavirus vaccines. A total of 26 regions, ranging from 8 to 23 amino acids, were identified as being conserved in at least one of the three different sequence alignments (Table 3). Fifteen fragments were identified in the pan-coronavirus alignment, 17 in the beta-coronavirus alignment and 12 in the human coronavirus alignment. Seven of them were detected in all three alignments. To identify potential T cell epitopes in these conserved regions, we searched the IEDB for described T-cell epitopes similar (>90% sequence identity) to the conserved peptides present in the CoV-2 consensus sequence. Interestingly, the majority of the conserved regions contained several matches, most of which were described epitopes derived from SARS-CoV. In total, 125 similar epitopes were identified, from all but two of the conserved regions (Table 3). The similar epitopes were found to be derived from the following organisms; SARS-CoV: 71, Human coronavirus 229E: 1, Alphacoronavirus 1: 1, Unknown origin: 3, and Homo sapiens: 47. Interestingly, 24 out of 26 fragments contained the described SARS-CoV T cell epitopes, indicating that these regions are immunogenic in humans and reinforcing the idea that some degree of cross-reactivity among coronavirus can be expected [11,58]. Also, the majority, i.e., 40 of the 47 human epitopes, clustered around one single region conserved in the beta-coronavirus alignment (QGPPGTGKSH). Several conserved peptides have thus been identified, which could potentially contain epitopes cross-reactive among different Coronavirus species. These conserved peptides can thus provide valuable information to understand if the immune response to SARS-CoV-2 is affected by previous infection with other coronaviruses and for pan-coronavirus vaccine design (Figure S2).