Messengers of hope: two mRNA Covid-19 vaccines herald a new era for vaccinology

How do they ensure that antibodies for the spike protein don't interfere with other processes in the body? E.g. if the spike protein bears a sufficient resemblance to part of another protein expressed by healthy human tissue, is there a risk of an immune response? Presumably the Phase 1 trial would sort that out for the most part, just wondering if there is any kind of ability to screen for that ahead of time.

This is the part I find especially exciting:<p>&gt; What is perhaps most exciting is the potential for mRNA as a rapid and generic platform for any desired immunogen(s). As upstream computational design and downstream processing and manufacture are standardized, custom work will mostly involve optimizing specific mRNA constructs to express efficiently in cells of interest.<p>It&#x27;s always interesting to me when we shorten feedback loops like this. For example, could this significantly improve flu vaccines by allowing them to be more up-to-date? How much more quickly can we squash the next pandemic? Could we respond rapidly enough to help with common colds?

How does the immune system keep a memory of what every single non-foreign protein looks like so that it can recognize foreign ones? That&#x27;s the most amazing thing here, to me.

What is the error rate in mass production of mRNA? What can mRNA with a few flipped&#x2F;wrong molecules do?

&gt; The new nucleoside-modified mRNA vaccines are chemicals that have been almost fully disclosed. They incorporate a trinucleotide cap 1 analog ((m27,3′-O)Gppp(m2′-O)ApG), contain N1-methylpseudouridine instead of uridine, and encode an optimized (P2-mutated) full-length S glycoprotein encapsulated in lipid nanoparticles (LNPs) containing polyethylene glycol and cholesterol. The BNT162b2 LNP also contains (4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) and 1,2-distearoyl-sn-glycero-3-phosphocholine, whereas Moderna’s LNP contains SM-102 (most likely heptadecan-9-yl 8-((2-hydroxyethyl)(6-oxo-6-(undecyloxy)hexyl)amino)octanoate) and 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG). ...<p>I&#x27;ll disagree here. Imagine I tell you a white powder of pure molecular composition is made up of just four elements: carbon; hydrogen; nitrogen; and oxygen. Would you ingest it?<p>It could be strychnine (poison) or glycine (an amino acid). You have no way of knowing.<p>Likewise, the physiological effects lipid nanoparticles (LNPs) are still mysterious. First, the exact composition isn&#x27;t known or even revealed in the FDA filing (thus the &quot;most likely&quot; above). Second, even given known composition, there&#x27;s no way to know how large, how stable, or how aggregated these particles are or what any of that means.<p>The model for LNPs that gets most widely discussed is an artificial cell membrane. There&#x27;s a water-filled center surrounded by a bilayer of lipid (grease). These particles may show variable sensitivity to degradation depending on how administered, composition, size, shape, trace impurities, and so on. For example, Moderna&#x27;s vaccine contains cholesterol, presumably for the same reason our cells do - to modulate membrane fluidity. It&#x27;s not clear just yet how persistent LNPs might be and what effects they might show, separate from the RNA payload.

So one of my takeaways from all of this is we cannot wait long enough based on current methods anymore. This virus is just one and it is likely to get worse. We need to invest now into large scale computer simulation of vaccines or things will become much worse. There is risk here, however I feel strongly that if we do need to move faster or today will become normal and that cannot become the normal! I read that most of the vacancies only took a few weeks for the scientist to create, however the current testing methods are why we are nearly 9 months to delivery. We as a society have to invest on new methods to move forward creation to delivery faster.<p>I am not claiming any expertise here - I majored in Biochemistry but never finished (moved to tech). I do have 14 doctors &#x2F; geneticist &#x2F; infection disease specialist in my family that share this view.

&gt; The new vaccines were 90 percent and 94.5 percent effective, said Mr. Paul, Republican of Kentucky and a trained ophthalmologist. And “naturally acquired” Covid-19 was 99.9982 percent effective, he claimed.<p>This is a good point, since you can&#x27;t get COVID a second time if you&#x27;re dead.

How do they classify something like this as safe for the long term if long term experiments are not conducted? Is there any substitute for time trials for drugs other than these new vaccines? These are the questions my relatives are asking me and my answers are I don&#x27;t know, I don&#x27;t. The scientific community needs to do a better job of communication. Why are we confident that a trial of only three months is sufficient when the only efficacy test for long term effects is long term trials?

Should I get vaccinated if I have already been infected with COVID?

&gt; For both products, adverse events elevated in the vaccine arm of the trial included ..., lymphadenopathy, nausea, erythema, Bell’s palsy and appendicitis.<p>If those are the bad side effects of the two vaccines that didn’t make the cut yet, what about the two that did?

&gt; Unlike DNA vaccines, mRNA vaccines do not have to cross the nuclear envelope, they pose no risk of genomic integration, and they work in both dividing and non-dividing cells.<p>This reads too much like a whitepaper &#x2F; marketing material.<p>Of course mRNA doesn’t cross the nuclear envelope. It doesn’t mean that it’s not a potential danger to the cells, though.<p>I’m not anti-vax. But, I don’t want to gloss over the danger with vaccines that were fast-tracked and now will be given to a few billion people.<p>What could go wrong? Lots, but if we don’t take it, that could be much worse.

Can someone with a good understanding of virology and a passable understanding of code explain to me how mRNA vaccines are not a regex, and don&#x27;t have the hazards of a regex?<p>What I mean is if the mRNA vaccine causes antigens that respond to a partial match of c-19 dna segments, which is how it is effective against even yet-to-be-developed spike proteins, isn&#x27;t it necessarily associated with the hazards of fuzzy matching we have with regexes?

They just need to get a hold on the allergic reactions..

correct me if I&#x27;m wrong but haven&#x27;t all the mRNA vaccines skipped human studies &#x2F; have &#x27;emergency use&#x27; certification

I think the incredibly historic accomplishments of these vaccines are unfortunately dulled quite a bit in this moment by the practical issues of how badly the US government and states are still bumbling the distribution of the vaccines.<p>I&#x27;m not talking the mundane details of the logistics of shipping, etc. getting those boxes out. That&#x27;s well understood. I&#x27;m talking strategy of who gets vaccinated, how they find out, how they get in line to receive the vaccine. How government tracks and ensures that the population is getting to an effective level of immunity.<p>I have not seen a whiff of that information and management system being put in place. We&#x27;re still random walking our way through this crisis. CVS has more information on the vaccination status of people in the country than the government does, for fuck&#x27;s sake.<p>It&#x27;s almost as if we&#x27;re leaving it to everyone to figure it out themselves, or on a voluntary basis.<p>Do <i>you</i> know how you&#x27;re supposed to get the vaccine? Has anyone contacted you or given you information? Have you seen any information on when <i>you specifically</i> are to sign up to receive the vaccine?<p>A more contagious&#x2F;virulent variant of the virus was just detected in Colorado, today. And we&#x27;re still letting a patchwork of counties figure it out as it comes.

It&#x27;s ok. If you start to suffer from a persistent autoimmune reaction, I&#x27;m sure there&#x27;s a therapeutic you can take for the rest of your life that only costs about 30k a month.