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Saying that a vaccine is $95\%$ efficacious is neither claiming that it works $95\%$ of the time nor that it protects $95\%$ of its recipients.† Rather, a $95\%$ efficacy means that—during the clinical trial in which half the subjects had been vaccinated and half hadn't—among those who eventually developed the disease, the ratio of those who had been ...


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I'm going to answer this one with a No. Outside of a simple simulation with very unrealistic constraints, we can't know the basic parameters to generate such a number. From an omniscient point of view there would be some number where this becomes inevitable, but from that point of view we could say it is inevitable or impossible right now. Some aspects to ...


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Epidemiological modeling If a virus is able to change so that it renders previous vaccination inefficient, reinfecting those who were previously vaccinated, one could describe this process using epidemiological SIS model (Susceptible-Infected-Susceptible) or its modification that includes a vaccinated group (like SISV model), and indeed estimate how quick ...


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As was observed (by others) under related q's here on material from that site, it seems Pfzier/BioNTech has done a global optimization to increase CG contents in the sequence, generally thought to be beneficial to mRNA expression (in addition to all the other things they've done, like U -> m1Ψ global substitution, specific to mRNA therapeutics). That (...


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The other answer is a bit convoluted IMHO. First note that as the article cited notes, that's not actually CCA -> CCU but CCA -> CCΨ; they only used ASCII for convenience. Furthermore, these three all code for proline as the article also notes. Second, Ψ stands for pseudouridine and it's the golden discovery of Kariko and colleagues (which made mRNA ...


0

This cartoon imagines that, rather than sacking Troy, the Greek soldiers inside were planning to help the Trojans recognize dangerous aliens who were preparing to attack. The horse represents the viral vector that carries the genetic material for producing the antigens that the immune system needs to learn to detect. The vaccine fails because the Trojans ...


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Yes, the cartoon is a description of immune action. Traditionally shown is first exposure being a vaccine, and the second exposure being the bad virus being destroyed. However, this cartoon is describing viral vector immunity. The first exposure is a viral vaccine. This alerts and educates the immune system about not just the intended antigen, but also the (...


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Viral vector only serves to deliver to cells the proteins/mRNAs necessary for triggering the immune response. In this sense it is like a Trojan horse - it is not supposed to cause suspicion, since otherwise it fails. In this case the immune system recognizes the vector as a dangerous virus, destroing it before it delivers its load. I find this xkcd rather ...


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I will try here to sketch an answer starting from where @MattDMo left off. Question: How do we evaluate possible long-term side effects of a vaccine? (With specific application to the recently authorized vaccines for SARS-CoV-2). Phase IV clinical trials As @MattDMo has pointed out, the definitive answer can be given only in the Phase IV of the clinical ...


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The two stop codons are obviously to prevent read-through of the termination codon. Why this should be necessary is not clear to me, but the following may be relevant: The synthetic mRNA differs from the natural mRNA in a particular respect that is easier to explain with reference to the transcript map of the virus, below. The two ORFs 1a and 1b are ...


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The article mentioned says: "Why would you do that? As noted above, our immune system takes a very dim view of ‘exogenous’ RNA, RNA code coming from outside the cell. To evade detection, the ‘U’ in the RNA was already replaced by a Ψ. However, it turns out that RNA with a higher amount of Gs and Cs is also converted more efficiently into proteins, And ...


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To enhance stability and translation efficiency according to {1}: The 5′UTR (TEV) [8,21] and 3′ UTR (F-I) of this construct have been shown to enhance stability and translation efficiency, as has the 100-nucleotide poly(A) tail interrupted by a short linker (A30LA70, where L = GCAUAUGACU) [22] References: {1} Stadler, C., Bähr-Mahmud, H., Celik, L. et al. ...


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You are correct that we have been creating and approving vaccines for a very long time, so the procedures for looking at efficacy and side effects of vaccines in general long-term are quite well developed. They occur via so-called "Phase IV" trials, also known as post-marketing surveillance. However, one complicating factor with at least the Pfizer/...


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