(Side note: You wouldn't use CRISPR nor HeLa cells, but rather traditional cloning techniques + any of a number of other cell lines traditionally used for recombinant protein production. But that's tangential to your question.)
I'm far from an expert here, but anything involving cell culture is generally thought to be pretty expensive. The media is expensive, other culture conditions can add to the cost as well (e.g. continuous supply of CO2 for mammalian cells), transfection reagents are expensive, and you have to expend a lot of effort keeping out bacterial/fungal/viral contamination. The inherent variability in biological processes means that you have to deal with batch-to-batch variability in your recombinant protein product, which... (read more)
What name would you use to talk about a chain of two or more amino acids?
Yeah I don't know if there is a term that's not super clunky like "amino acid-based polymer." But I think the more fundamental issue is that it's weird to group peptide-based and protein-based vaccines together for the claims that you're making. You can't both fend off the claim that "whole protein domains are better immunogens than peptides because they have more native-like folds" by saying that "proteins ARE peptides, and are included in my category" AND say that "it's irresponsible for us as a society not to have invested more in peptide-based vaccines because they're so cheap... (read more)
I suspect that the low efficacy of mRNA vaccines (only 95% - low is relative) is likely because they're only targeting the spike protein, which apparently has 'high mutant escape potential'. We have a LOT more information about the virus now than we did when the mRNA designs were finalized. If companies had been allowed to make mRNA vaccine updates without resetting all the clinical trials, I believe we'd have a substantially better/stronger vaccine than just 95%, with a single shot instead of two.
Eh, I guess I'm skeptical that it's that easy, even now, to make changes to the mRNA vaccines that would bring us from 95% up to 100% protection (against... (read more)
Proteins are peptides. When you give whole-proteins, protein domains or nanopeptides (short peptides). With peptide vaccine I mean a vaccine that contains peptides opposed to one that contains mRNA.
It's worth noting that calling proteins peptides is not standard terminology. If you say "peptide-based vaccines," it's generally understood that you're not including protein-based vaccines (also known as subunit vaccines). And in your original post, it does sound like you are making this distinction. If you aren't making this distinction, then it doesn't quite make sense to decry the lack of focus on "peptide-based vaccines" (including protein-based ones) as opposed to mRNA when there are plenty of protein-based candidates (most notably Novavax) in advanced... (read 401 more words →)
The mRNA technology seems to provide no benefit over simply giving the peptides directly but the mRNA researchers really wanted to do fancy research on mRNA.
I think you're giving mRNA vaccines too little credit and peptide-based vaccines too much.* I haven't looked into peptide vaccines much at all but my general impression is that they don't work that well as a class. Hundreds of peptide vaccines have entered the clinic with no approvals (albeit, not all against infectious diseases, many against cancer which is more difficult) — without looking into the details, I couldn't tell you exactly why, but my guess would be lack of efficacy. When you present something to the... (read more)
Looks like we have at least one case of reinfection with one of the new variants containing the E484K mutation (this isn't the South African variant, rather from the Brazilian lineage where E484K independently arose).
Potential counterargument against the above: Well, yes, any individual pharma company might only have one shot, but as a society we could have many different untested vaccine candidates going out to people all at once. We already have a risk diversification mechanism by having many different vaccine candidate options, so we don't need to further avoid risk by doing trials on all of them. And we also don't have to give untested vaccines to literally everybody, just small populations at first.
Response to the counterargument: If the proposal is to give a bunch of untested vaccine candidates to people early on in the pandemic before knowing for sure how they work, haven't you just reinvented clinical trials? Maybe a conception of them that is faster and to a larger population, but still fundamentally the same thing?
So I think that you're right to point out the bias that many experts have in overprioritizing wanting to avoid harm from a vaccine at the cost of ongoing deaths from the pandemic. That's likely a very strong consideration playing into their judgments here, and one that should be fought against.
That being said, I think another concern that is underappreciated in these debates is lack of efficacy, rather than lack of safety. What if—and this is probably more likely—a vaccine doesn't result in any harm, but also just doesn't do anything to prevent disease? How much time have you spent getting pharma to invest time and resources into developing a manufacturing process... (read more)
Anyway, these are in a domain that constitutes about 20% of human neutralizing antibodies and are quite possibly somewhat immunologically relevant.
Can you point to where I can find more about this estimate? I'm starting to think of the NTD as more immunodominant than that. E.g., out of 19 potently nAbs isolated here, about half were RBD-targeted and half were NTD-targeted. Here you see similar or more NTD-targeted antibodies in the convalescent plasma of 2 patients than RBD-targeted antibodies (both are outnumbered by anti-S2 antibodies, but I'm—perhaps naively—assuming those are mostly non-neutralizing). Deletions in the NTD also seem to be selected for in response to immune pressure (e.g., in response to convalescent plasma... (read more)
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Hi Luke, thanks for your question!
It's not that we want to go the FDA route per se – the tech that we're developing would simply require it. The expertise that we have at PanLabs is mostly in synthetic biology, which lends itself to developing new biologic drugs, which are regulated by the FDA. However, we're not ruling out the possibility of going the drug-free route with future research programs; it would just be a matter of capacity-building first.