Yeah, the pfizer vaccine looks like it just uses mRNA to construct the RBD (receptor binding domain) of the spike protein, which is about two hundred amino acids long. None of the default 9 peptides in gen 9 radvac are for that domain. See page 40 of the whitepaper for the full spike protein sequence; the highlighted blue is the RBD, and the short underlined sequences are peptides selected for the vaccine.
The moderna vaccine uses mRNA to construct pretty much the whole spike protein, including the RBD. This has overlap with 3 of the 9 radvac peptides.
This paper has one of the better lists I’ve found of commercial vaccine types:
From the list in that paper, it seems like pretty much all commercial products are using spike as the primary target; radvac is unique in that it also targets ORF and Nuc.
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Amusingly enough, when talking about the commonly targeted spike protein RBD sequences, the radvac whitepaper lists on page 29: “Spike 450-500; ACE2 binding residues of the RBD (Zhang et al); low degree of conservation; probably moderate to high mutant escape potential”. So they pretty much called it in regards to the new virus strains with mutations like E484K.
Another radvac whitepaper quote, which seems to line up with my independent research: “It is important to note that most published neutralizing antibodies target Spike RBD, as do many vaccines in commercial development. However, given the high degree of mutability of the RBD portion of Spike, it is highly recommended to identify and select targets outside the RBD because of mutant escape potential.”
And lastly, more specific to why no RBD peptides were selected, page 34:
“Therefore, rather than focusing on ACE2-binding epitopes in the highly mutation prone RBD to inhibit virus binding to the ACE2 receptor, we targeted these B-cell epitopes in the highly conserved portions of the Spike protein to strategically neutralize proteolytic cleavage and membrane fusion. Furthermore, all three are bound by antibodies present in the sera of large fractions of convalescents, and they produce among the highest signals in linear epitope mapping studies, which are far higher than signals measured for binding to any linear epitope in the RBD.”
Yeah, the pfizer vaccine looks like it just uses mRNA to construct the RBD (receptor binding domain) of the spike protein, which is about two hundred amino acids long.
Holy crap, the entire RBD!? These mRNA vaccines are a technical marvel, I’m amazed they can actually deliver that into a cell safely.
I really hope you write up a post on your learnings, the comments have been amazing and way more in-depth than my knowledge.
Yeah, the pfizer vaccine looks like it just uses mRNA to construct the RBD (receptor binding domain) of the spike protein, which is about two hundred amino acids long. None of the default 9 peptides in gen 9 radvac are for that domain. See page 40 of the whitepaper for the full spike protein sequence; the highlighted blue is the RBD, and the short underlined sequences are peptides selected for the vaccine.
The moderna vaccine uses mRNA to construct pretty much the whole spike protein, including the RBD. This has overlap with 3 of the 9 radvac peptides.
This paper has one of the better lists I’ve found of commercial vaccine types:
https://www.sciencedirect.com/science/article/pii/S2319417020301530
From the list in that paper, it seems like pretty much all commercial products are using spike as the primary target; radvac is unique in that it also targets ORF and Nuc.
-----
Amusingly enough, when talking about the commonly targeted spike protein RBD sequences, the radvac whitepaper lists on page 29: “Spike 450-500; ACE2 binding residues of the RBD (Zhang et al); low degree of conservation; probably moderate to high mutant escape potential”. So they pretty much called it in regards to the new virus strains with mutations like E484K.
Another radvac whitepaper quote, which seems to line up with my independent research: “It is important to note that most published neutralizing antibodies target Spike RBD, as do many vaccines in commercial development. However, given the high degree of mutability of the RBD portion of Spike, it is highly recommended to identify and select targets outside the RBD because of mutant escape potential.”
And lastly, more specific to why no RBD peptides were selected, page 34:
“Therefore, rather than focusing on ACE2-binding epitopes in the highly mutation prone RBD to inhibit virus binding to the ACE2 receptor, we targeted these B-cell epitopes in the highly conserved portions of the Spike protein to strategically neutralize proteolytic cleavage and membrane fusion. Furthermore, all three are bound by antibodies present in the sera of large fractions of convalescents, and they produce among the highest signals in linear epitope mapping studies, which are far higher than signals measured for binding to any linear epitope in the RBD.”
Holy crap, the entire RBD!? These mRNA vaccines are a technical marvel, I’m amazed they can actually deliver that into a cell safely.
I really hope you write up a post on your learnings, the comments have been amazing and way more in-depth than my knowledge.