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In a paper entitled "Progress and Prospects on Vaccine Development against SARS-CoV-2", the authors write the following in section 2.5:

"Compared with S, N, and M protein, E protein is not suitable for use as an immunogen. For one reason, it consists of 76–109 amino acids in different coronaviruses with channel activity, thus the immunogenicity is limited. Studies have shown that SARS-CoV E protein is an important virulence factor, and the secretion of inflammatory factors IL-1β, TNF, and IL-6 are significantly reduced after knocking out E protein"

Question

Why does the fact it consists of 76–109 amino acids in different coronaviruses with channel activity imply its immunogenicity would be limited?

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  • $\begingroup$ sciencedirect.com/science/article/pii/S0168170215001136 in 2015 thought the E protein would be a good target. I dont understand. $\endgroup$ – Polypipe Wrangler May 4 at 6:04
  • $\begingroup$ @PolypipeWrangler Thanks for your comment. Doesn't that paper comment on how removing the E protein weakens the virus and therefore SARS-CoV with the E protein removed might be a candidate for an attenuated vaccine? It doesn't discuss whether the immune system can be trained to go after the E protein itself. $\endgroup$ – Anony-mouse May 4 at 10:30
  • $\begingroup$ You are right, viroids without E protein were weakly infectious. I will try to follow the citation chain forward to see if anything interesting turns up. $\endgroup$ – Polypipe Wrangler May 4 at 10:42
  • $\begingroup$ @PolypipeWrangler I actually think it's useful to keep your comments because that is how we all learn. $\endgroup$ – Anony-mouse May 4 at 10:49
  • $\begingroup$ virologyj.biomedcentral.com/articles/10.1186/s12985-019-1182-0 is a 2019 article on c-virus proteins. out a year ago. $\endgroup$ – Polypipe Wrangler May 4 at 10:58
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The article implies E proteins are quite different between the previous known strains - so a vaccine targeted against E protein may only affect a limited range of strains.

But when I do a BLAST search on CS079032.1 I find nearly all the protein sequences are identical (results below).

enter image description here

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  • $\begingroup$ Thanks for posting an answer. Maybe I have misunderstood, but I don't see how this answers the specific question I asked though? $\endgroup$ – Anony-mouse May 4 at 12:03
  • $\begingroup$ Thats OK. The line from the article about 76-109 amino acids implies that the E proteins are too diverse for a useful vaccine - but that is not what I am finding. $\endgroup$ – Polypipe Wrangler May 4 at 12:15
  • $\begingroup$ I could be wrong but aren't the authors of the paper in my question implying the E protein won't provoke a strong immune response (not that it's not useful as an immunogen due to variation between strains)? I'm trying to understand the reasoning underlying their claim the immunogenicity would be limited. $\endgroup$ – Anony-mouse May 5 at 17:49
  • $\begingroup$ I hadn't found evidence that the E protein has reduced immunogenicity. I dont know why they say so. $\endgroup$ – Polypipe Wrangler May 5 at 19:57
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Firstly, for better immunogenicity, we should select short peptide of approximately 20 amino acids. Longer peptide will definitely increase the immunogenicity, but that also increase the possibility of cross-reactivity. So, shorter peptide is more specific.

And secondly channel activity means, it contains more hydrophobic amino acids, so that it can form the transmembrane domain. But hydrophobic residues will decrease the solubility of a immunogenic peptide in the aqueous solution.

Reference: https://www.proimmune.com/custom-peptides/

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