Thanks for the write up! I started to do this myself but quickly found I was a bit confused on how to even order the peptides. I was expecting to be able to search product lines but.… Not really possible. So...is the process to simply identify some suppliers (not hard to find with Google) give them the amino acid sequences in the instructions and ask for a quote? (Hit that initial speed bump and have not gotten back to looking for phone numbers or customer support chat windows.)
Just a thought. So this doesn’t scale well for storage and shipping it sounds but production is pretty simply and materials seem to be fairly durable for storage (I don’t think the peptides decay quickly). If so, couldn’t the model be that a small lab at the many, many, many pharmacy (or at lest the big chains) stores make batches for the appointments they have scheduled. Given that the delivery method seem to be better (thanks for bringing that up—was going to ask) and that should take out a lot of the supply chain bottlenecks we have been seeing I would think. (Or once the transition and supporting setup/infrastructure locally is done.)
The other question, having taken this is there any concern about being required later to also take one of the officially blessed vaccines. This might be even more important is you don’t show the antibodies for some reason but have reacted to the vaccine. I don’t think I completely read the radvac white paper but don’t recall them having any section that might have spoken to that.
So...is the process to simply identify some suppliers (not hard to find with Google) give them the amino acid sequences in the instructions and ask for a quote?
The one I used had an online “custom peptide synthesis” order form. I just pasted in the sequences, checked a few boxes, it autogenerated the price tag on checkout screen, and then I hit the order button. (It actually took a bit longer than that since both my girlfriend and I triple-checked the sequences.) I specifically avoided any suppliers which would have made me talk to a salesperson to get a quote—that crap is a strong sign of Maziness.
having taken this is there any concern about being required later to also take one of the officially blessed vaccines
Dentin had a comment on this somewhere in this rapidly-growing comment section, saying that the commercial vaccines use different epitopes and should therefore play well together with this one.
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.
The one I used had an online “custom peptide synthesis” order form.
How about sharing the link?
Dentin had a comment on this somewhere in this rapidly-growing comment section, saying that the commercial vaccines use different epitopes and should therefore play well together with this one.
Besides different epitopes, if the RadVac vaccine gives you an immune reaction in the mucosal immune system and the other vaccines give you a immune reaction in the normal immune system you will want both.
Absolutely obviously yes. I have some level of concern that this post will go viral (ha ha), get a lot of attention outside of lesswrong, and the company I’m working with will cancel my order because it’s “covid misinformation” related.
The FDA might be slow and take months to approve safe things while thousands of people die per day, but they’re perfectly capable of announcing an immediate and indefinite peptide ban in under a day because a news article crossed the wrong person’s desk.
Thanks for the write up! I started to do this myself but quickly found I was a bit confused on how to even order the peptides. I was expecting to be able to search product lines but.… Not really possible. So...is the process to simply identify some suppliers (not hard to find with Google) give them the amino acid sequences in the instructions and ask for a quote? (Hit that initial speed bump and have not gotten back to looking for phone numbers or customer support chat windows.)
Just a thought. So this doesn’t scale well for storage and shipping it sounds but production is pretty simply and materials seem to be fairly durable for storage (I don’t think the peptides decay quickly). If so, couldn’t the model be that a small lab at the many, many, many pharmacy (or at lest the big chains) stores make batches for the appointments they have scheduled. Given that the delivery method seem to be better (thanks for bringing that up—was going to ask) and that should take out a lot of the supply chain bottlenecks we have been seeing I would think. (Or once the transition and supporting setup/infrastructure locally is done.)
The other question, having taken this is there any concern about being required later to also take one of the officially blessed vaccines. This might be even more important is you don’t show the antibodies for some reason but have reacted to the vaccine. I don’t think I completely read the radvac white paper but don’t recall them having any section that might have spoken to that.
Again, great write up and contribution.
The one I used had an online “custom peptide synthesis” order form. I just pasted in the sequences, checked a few boxes, it autogenerated the price tag on checkout screen, and then I hit the order button. (It actually took a bit longer than that since both my girlfriend and I triple-checked the sequences.) I specifically avoided any suppliers which would have made me talk to a salesperson to get a quote—that crap is a strong sign of Maziness.
Dentin had a comment on this somewhere in this rapidly-growing comment section, saying that the commercial vaccines use different epitopes and should therefore play well together with this one.
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.
How about sharing the link?
Besides different epitopes, if the RadVac vaccine gives you an immune reaction in the mucosal immune system and the other vaccines give you a immune reaction in the normal immune system you will want both.
I don’t want people giving the company crap if this post ends up very widely read. If anyone would like a link, PM me.
Are we really living in times where “company helped people with doing something themselves against COVID-19” would be problematic PR-wise?
obviously yes?
Absolutely obviously yes. I have some level of concern that this post will go viral (ha ha), get a lot of attention outside of lesswrong, and the company I’m working with will cancel my order because it’s “covid misinformation” related.
The FDA might be slow and take months to approve safe things while thousands of people die per day, but they’re perfectly capable of announcing an immediate and indefinite peptide ban in under a day because a news article crossed the wrong person’s desk.
About the “viral” part. This post is currently at the top of HN: https://news.ycombinator.com/item?id=26022750
Ugh. Thanks for the link.