mRNA vaccines — a new era in vaccinology

land on one side of the political spectrum. I know some. It's everything from "it's the mark of the beast" to "I'm not so sure about this". What really underlies it is a deep, irrational selfishness that doesn't want to do a damn thing, even if, and especially if COVID doesn't seem that risky for that person. That whole line of reasoning is a fail. People who want the pandemic to be over know that vaccination is the only way. Sitting on your ass, no matter what is in your head, and being another vessel for this shit to mutate is actively prolonging it. So yeah, I absolutely pounce on ignorant people who are prolonging this.

switching sequential steps in the process to be parallel. > We have absolutely no idea if there are any long term side effects of these vaccines. This isn't a meaningful claim for 2 key reasons. There has never been a vaccine that had serious side effects that did show up shortly after vaccination[2]. The history of mRNA treatments began as an experiment in gene therapy, but has largely ben abandoned because the effects never lasted long enough. As of 2020 this is an ongoing area of research[3]. No one has figure out how to stabilize mRNA so that it has long lasting effects. > Both candidates Biden and Harris They're both craven, ignorant politicians, who cares what they said when the other guy was in power. [1] https://www.nature.com/articles/nrd.2017.243 [2] https://www.cdc.gov/vaccinesafety/concerns/concerns-history.... [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076378/ [edit] All that said, I am no pro mandate but seriously you should all voluntarily go get vaccinated IMHO.

sequence. > Or is there a "close enough!" thing in the immune system, where it can be a little different and still be targeted by the immune system? It depends on how different the sequence is. For instance, if it is a little different the immune response should be very similar because, for example, the three-dimensional conformation of the spike protein chain should remain very similar as well. This is why the vaccines can be effective against several SARS-CoV2 variants.

(far from it) but some of them work better than others, and the current lipid nanoparticle ones are the current state of the art – the LNPs themselves activate the innate immune system, but in a way that doesn’t seem to trigger too much of a self-defeating cytokine response. It’s a useful enough effect that they’re being proposed as adjuvant additions to other, more traditional vaccines for that effect alone. Me: Both the LNPs and the mRNA itself stimulate the immune system. Basically the vast majority of work in mRNA drugs for the last decade has been to try to reduce that-- and associated toxicity and unpredictable clearance. Meanwhile, the (right amount of) immunogenicity has been accepted as a feature in vaccine candidates. And in a series of journal articles e.g. in Frontiers in Immunology: https://www.frontiersin.org/articles/10.3389/fimmu.2018.0222... "This was observed in the case of administration of empty PEGylated liposomes, which were able to elicit IgM response in an in-vivo model. (27, 28). Besides their potential to deliver various immune stimulators to the specific sites as well as into the deep tissues where vaccine molecules alone may not able to reach, these NPs have also been exploited as adjuvants to augment immunogenicity of vaccine candidates." Nature / npj Vaccines: https://www.nature.com/articles/s41541-020-0159-8 "Thus, multi-antigen candidates necessitate a significant amount of LNP for a given dose. LNPs are known to have inherent adjuvant properties." Nature / npj vaccines: https://www.nature.com/articles/nrd.2017.243 "Exogenous mRNA is inherently immunostimulatory, as it is recognized by a variety of cell surface, endosomal and cytosolic innate immune receptors (Fig. 1) (reviewed in Ref. 35). Depending on the therapeutic application, this feature of mRNA could be beneficial or detrimental. It is potentially advantageous for vaccination because in some cases it may provide adjuvant activity to drive dendritic cell (DC) maturation and thus elicit robust T and B cell immune responses. ... The immunostimulatory properties of mRNA can conversely be increased by the inclusion of an adjuvant to increase the potency of some mRNA vaccine formats. These include traditional adjuvants as well as novel approaches that take advantage of the intrinsic immunogenicity of mRNA"

packed endothelial cells and may thus contribute to oedema 169. Another study showed that extracellular RNA promoted blood coagulation and pathological thrombus formation 170. Safety will therefore need continued evaluation as different mRNA modalities and delivery systems are utilized for the first time in humans and are tested in larger patient populations.

transcript expression--it's just too hot. CureVac founder and arguably the first person to really drive the idea of an mRNA vaccine into the clinic is Ingmar Hoerr, but his company started before the idea of modified chemistry. He is a fantastic scientist, but ultimately CureVac came too soon and has triple-downed on canonical uridine. Another issue is they likely can't get FTO so they don't really have a choice. As for blogs/twitter accounts, none of the mRNA people are active on social media likely because the stakes are just too high right now. If you're interested in mRNA beyond vaccines, check out Sek Kathiresan on twitter. He's active. He's the CEO of Verve. Worst kept secret of the gene editing (e.g., CRISPR) world is that everyone is pivoting to using mRNA for expression of the editing enzymes (e.g., CAS9, ADAR, APOBECs).