Comparing infected patients with those who have not been exposed to the coronavirus, this team went through the list of 25 viral proteins that it produces. In the CD4+ cells, the Spike protein, the M protein, and the N protein stood out: 100% of the exposed patients had CD4+ cells that responded to all three of these. There were also significant CD4+ responses to other viral proteins: nsp3, nsp4, ORF3s, ORF7a, nsp12 and ORF8. The conclusion is that a vaccine that uses Spike protein epitopes should be sufficient for a good immune response, but that there are other possibilities as well – specifically, adding in M and N protein epitopes might do an even more thorough job of making a vaccine mimic a real coronavirus infection to train the immune system.
As for the CD8+ cells, the situation looked a bit different. The M protein and the Spike protein were both strong, with the N protein and two others (nsp6 and ORF3a) behind it. Those last three, though, were still about 50% of the response, when put together, so there was no one single dominant protein response. So if you’re looking for a good CD8+ response, adding in epitopes from one or more of those other proteins to the Spike epitope looks like a good plan – otherwise the response might be a bit narrow.