Talk:RNA vaccine/Archive 1

Archive 1

Archive 2

Archive 3

mRNA

mRNA should be spelled out at first occurence. — Preceding unsigned comment added by Gerdami (talk • contribs) 07:22, 24 April 2020 (UTC)

Grammar Issue

I'm not a subject expert so I do not know how to fix the incomplete second sentence in the second paragraph. Any ideas?

The RNA sequence codes for antigens, proteins that are identical or resembling those of the pathogen.

DavidHarkness (talk) 03:04, 3 August 2020 (UTC)

RNA sequence is the subject, codes is the verb, antigens is the object, the sentence is fine. ~ (Just some rando...)

Yes, this grated with me the first time I read it too. "Codes" is used here as a verb, which can read a little oddly if you are unused to it. Tedmarynicz (talk) 12:38, 9 November 2020 (UTC) (Not a rando...)

Yes but. I didn't pause over the sentence in context, but see it now as problematic. Edit to: The RNA sequences are the molecules that code for antigen proteins that are identical to or resemble those of the pathogen.

Approved for human use

The article states: "Currently, there are no RNA vaccines approved for human use.". I think Russia's SARS-CoV2 vaccine is an RNA vaccine ([1]) and they approved it for human use ([2]) 212.51.129.95 (talk) 09:49, 15 August 2020 (UTC)

Gam-COVID-Vac is not an RNA vaccine but uses the viral vector method.--Pontificalibus 16:10, 9 November 2020 (UTC)

History

The lede says this is "a new type", but it alludes to "clinical trials in the late 1990s", and there is no history section. What does "new" mean, what is the timeline here? int21h (talk · contribs · email) 19:54, 15 November 2020 (UTC)

I have added a history section and clarified the clinical trials from the 1990s were on aminals.

cf Cold chain and efficacy - What does this mean?

The lead currently states: "The fragility of the mRNA molecule requires cold chain distribution and low temperature storage, and may impair long-term efficacy.[1][4][5]" I find this confusing. Is this talking about problems of delivery and distribution? Or are we talking about the persistence of immunity? The vaccine mRNA does not need to persist long term for the development of long-term immunity. --Robert.Allen (talk) 21:38, 20 November 2020 (UTC)

I don't think it needs the term "long-term". The issue is that because mRNA degrades so fast, by the time somebody gets an injection, the mRNA present in the solution may be very low, thus impairing the effective efficacy. Probably also use "effective efficacy", as it obviously does not change the theoretical efficacy. 109.255.90.188 (talk) 12:46, 21 November 2020 (UTC)

Thanks, I think it's now clear. --Robert.Allen (talk) 19:02, 21 November 2020 (UTC)

vaccine not blue high lighted?

I'm trying to reference the vaccine page and the results are NO blue highlight. I suspect that the RNA vaccine is interfering with the blue highlight because of the vaccine in the similar headings. — Preceding unsigned comment added by Bgordski (talk • contribs) 08:26, 6 December 2020 (UTC)

You are not making any sense - the vaccine link in the paragraph above is blue-lined? You have made changes to the "accessdate" parameter in several refs in the article that is now appearing as red-lined (which will need to be fixed). You should not make technical changes in WP if it is not familiar to you; check out the WP:TEAHOUSE for help. thanks. 109.255.90.188 (talk) 11:23, 6 December 2020 (UTC)

FWIW: my screed on balance

The use of RNA in a vaccine has been the basis of substantial misinformation circulated via social media, wrongly claiming that the use of RNA somehow alters a person's DNA, or emphasizing the technology's previously unknown safety record, while ignoring the more recent accumulation of evidence from trials involving tens of thousands of people.

It's bad form to tell any group of people what they are ignoring when they advance an opinion, however silly it might appear to be, even from a relatively objective swoke perspective (swoke = science-woke):

Russell conjugation:

• I discern
• you discount
• they ignore

Very bad form.

———

Furthermore, the use of the word "accumulating" makes scientific process should like a rumbling train of inevitability.

Hardly. Because the world is a messy place, and this same scientific tradition has no shortage of historical black marks.

The completed studies were reasonably large, but they tested:

• a specific mode of production
• a specific mode of distribution and application
• a specific mode of collecting and evaluating reports of adverse outcomes
• over at most a short to moderate time horizon.

———

This mRNA delivery technology is a radical departure from traditional approaches. On paper, it looks like advantages all the way down, but ordinarily caution would reign in introducing a technology as substantially new and different as this technology.

We do not yet know that scaling up product at the drop of a pin to hundreds of millions of doses won't prove problematic.

We do not yet know whether the various national and regional health authorities can reliably duplicate the mode of distribution and application that the studies seemed to validate as safe.

The fact of the matter is that we've judged the global pandemic as severe enough in human cost to justify learning the rest of these lessons on the fly, using the general population as a massed pool of Guinea pigs.

For various reasons, some inherent in the new technology, odds are exceptionally good that this is a wise trade-off in pursuit of global health outcomes.

Nevertheless, it's rude beyond belief to seemingly accuse hesitant skeptics of simply ignoring what evidence we now have, as if anyone regards the evidence we now have in hand as entirely sufficient or ideal.

———

What we have in hand is a spectacularly good result, both in terms of efficacy and safety, from a rushed development project with few direct parallels in the whole of human history.

Our modern understanding of infectious disease goes back to the invention of the microscope, circa 1674, when we discovered 'animalcules' swimming around in common fluids, shortly after postulating that eggs are fertilized by tiny sperm.

Most of the current human population is on board with sex causing babies.

Not quite as many are on board with the infectious model of disease transmission—at least not enough to participate in a global public health response by covering their cake and snot-holes in public venues with a thin piece of cloth. We've been studying these little booger-buggers for 350 years now. It's hard to fathom how The Bad News Bible could deliver its cognitive payload quite this slowly, but apparently the bleat goes on.

Darwin's smaller claim, that species evolve in physical form through the incremental accumulation of hereditary change is perhaps now the most thoroughly supported major hypothesis in human history.

His larger lemma, that incremental hereditary change explains nearly all of the modern diversity of life has about a billion times less direct evidence (you can't print this kind of evidence out by the terabyte with automated sequencing machines). A five-million-year longitudinal study of genetic change and drift over wide range of plants and animals would be extremely useful—but still incomplete—in placing Darwin's larger lemma onto a secure footing. (We do have plenty of indirect evidence, this largely of the form that biologists have so far always seemed clever enough to concoct a story where evolutionary history such we have managed to observe just might have been entirely self-propelled by the mechanism of random mutation/selection via genetic heredity alone—or mostly alone, depending on your stance toward epigenetics.)

There remains a large segment of the human population who continue to choke on Darwin's smaller claim like a sharp chicken bone. Terabytes of genetic sequence data continues to pile up, and yet it seems to make hardly any dent on this insular subculture.

As for Darwin's larger lemma, it's already compelling in some lights, but actually I think many working biologists ought to temper their faith in this one pending actual direct evidence. It sure is a pity the first solid installment is going to take roughly 5 million years (though we might already have some tantalizing hints after the first 1000-year preamble).

So there it is: for every express train of human comprehension, there's also a milk run that circumnavigates Siberia. Trendy passengers in fancy business suits pull down the shades and believe too easily, while others clad in practical dungarees have yet to notice that the window mechanism contains such an incomprehensible modern accessory, and so they sit there dazed and blinded by the sun.

———

So where are we on modern vaccination technology?

• Forbes: Why Aren't Vaccines Given Intravenously? — 7 November 2017

Local responses to IM injections of vaccines aren't readily visible and haven't been systematically studied. Few animal model studies bothered to examine muscle tissue after an IM vaccine jab and the few that did found signs of intense, even long-term inflammation.

However, this issue remained both under-researched and unaddressed for decades, in hindsight seeming to await the revitalization of research into the innate immune system, something that only got galvanized in the late 1990s.

In the meantime, IM injections took firm root in vaccinology while modern medicine also took shape over the same time period and again, from convenience, IM became established as a predominant injection route and thus we reach present-day when most vaccines are IM jabs.

...

'Depot' effect: How this immunological dogma got started and brief assessment of its impact

Though practical and cosmetic considerations helped IM injections dominate vaccinology, another element absolutely crucial in doing so was a dogma that also explains why the IV route became a non-starter for vaccines.

Apart from discovering the adjuvant effects of aluminum salts, currently the most widely used adjuvant in human vaccines, Glenny's legacy looms over vaccinology and even immunology itself in the form of the dogma called the 'depot' effect.

No question, immunology was in its infancy in Glenny's time. Key players such as T and B cells were still decades away from being discovered.

The question still had to be answered though.

How to explain why adding aluminum salts to purified toxins such as diphtheria and tetanus vastly increased the immune responses (measured as antisera) they elicited?

Given the limited understanding of the immune system in the early 20th century, consensus soon coalesced around a physical explanation, namely, that the crystalline aluminum salt and its adsorbed antigen(s) remain at the site of injection as a depot, which would allow the antigen(s) to be released slowly over time to serve as continuing stimulus for sustained antibody production.

Clearly, IV injections couldn't sustain a 'depot' effect so they were never seriously considered for vaccines.

A mechanistic link between antigen-adjuvant 'depot' and robust immunity was challenged almost from the very beginning when animal model studies summarized in a 1950 book showed that strength of the immune response remained unaffected even if the injection site nodules containing antigen-adjuvant were surgically excised a mere 14 days after immunization.

However, with no other satisfactory answer forthcoming, the 'depot' effect took root and vaccinology more or less slumbered for decades, at least as far as trying to figure out how aluminum salts and other adjuvants boosted immune responses to the antigens conjugated to them.

The decades-long Rip Van Winkle-like slumber over how adjuvants augment immune responses got jolted in 1989 when Charles Janeway wrote a hugely influential article about, among other things, the immunologist's 'dirty' little secret, a play of words alluding to the fact that immune responses to purified antigens typically tend to be muted or non-existent unless accompanied by 'dirt', by which he meant adjuvants such as CFA (Freund's adjuvant) in animal models or aluminum salts in human vaccines.

Janeway's hypothesis was invigorated and validated by the discovery of the first mammalian Toll-like receptor (TLR) by his lab in 1997 followed in short order by discoveries of CLRs (C-type lectin) and NLRs (NOD-like receptor) and other pattern recognition receptor (PRRs) discoveries that offered a biological explanation for the adjuvant effect and opened the door to a molecular basis for understanding how the innate immune system operates and how it co-ordinates with and/or controls the Adaptive immune system.

Is the 'depot' effect important or even necessary now?

Though considerably weakened by the discovery of PRRs, it still retains some of its hold as an immunological dogma to explain the role of even PRRs since we don't yet fully understand how strong and long-lasting immunological memory forms nor how adjuvants work.

However, regardless of the need for antigen 'depot', today IM vaccine injections remain a mainstay.

So there it is (supplementary lemma): The history of vaccination is not precisely littered with vaccinologists entirely having their shit together on every sharp ramification.

———

Moral of the story: One or two hasty studies of thirty- or forty-thousand people, however brilliant the results, does not suffice to settle all pertinent concerns and worries over a novel vaccination technology. — MaxEnt 17:47, 17 December 2020 (UTC)

Hence, WP:FORBESCON. SandyGeorgia (Talk) 17:51, 17 December 2020 (UTC)

And the 1,500 word "essay" is not helpful. Why not simply suggest an edit? Graham Beards (talk) 18:31, 17 December 2020 (UTC)

@SandyGeorgia: exactly. As to the kvetching over the word "ignoring" - the assumption is that our readers are intelligent and rational; we are not attempting to persuade antivax loons through rhetorical finessing (indeed, the evidence is ignorance is so powerful, that would be futile anyway - people have literally died from COVID-19 insisting the disease is a hoax). So we neutrally report what the antivax loons are up to, and readers can pick the bones out of that! Alexbrn (talk) 18:35, 17 December 2020 (UTC)

Too COVID-19 centered?

There's a separate article for COVID-19 Vaccine. This article should be about mRNA vaccines, which don't always apply to COVID-19. It's a method that's been around for over 2 years. — Preceding unsigned comment added by Scuba Penguin (talk • contribs) 04:18, 20 November 2020 (UTC)

The COVID-19 vaccine article covers multiple types of platforms (established and novel). Outside of the COVID mRNA vaccines, there are no other rna vaccines, so it is important to mention them as practical examples (as well as the theory). 109.255.90.188 (talk) 08:27, 20 November 2020 (UTC)

Yes, obviously there is no problem mentioning the Covid-19 vaccines, but there are also several potential cancer vaccines currently in clinical trials, and for a while these were almost totally overlooked here. --Robert.Allen (talk) 20:47, 20 November 2020 (UTC)

Agreed. Have always shied away from editing on candidates that are too experimental as it can be wasted. There is lots of stuff from Moderna especially, but much of it went nowhere, although there is at least one exception that could have promise. 109.255.90.188 (talk) 12:49, 21 November 2020 (UTC)

Yes, it looks like they've already removed some of the candidate cancer vaccine trials from their website. --Robert.Allen (talk) 19:00, 21 November 2020 (UTC)

References

Life time of of RNA vaccines in cell?

I think this page is missing an explanation that mRNA used for such vaccines are usually not self-replicated and became quickly inactivated in the cell, as described in Messenger_RNA#Degradation. Otherwise, they would produce viral protein to infinity. Was anything published about the life time of COVID-19 vaccines in human cells and what types of cells?My very best wishes (talk) 16:19, 30 November 2020 (UTC)

It is a good point but the data from Moderna and BioNTech is pretty minimal at the moment (in fact, the article has commentary from Margaret Liu - one of the leaders in this field - wondering if the mRNA is really working and whether the 94% efficacy is really from the immune system moving to DEFCON #1 due to the injection of the vaccine. Why people who have just overcome the flu, are less likely to get serious COVID infections. If I see definitive refs on the mechanism of action of these vaccines, then will add. 109.255.90.188 (talk) 00:19, 1 December 2020 (UTC)

I hope they will be forced to disclose all molecular details, such as the exact sequence of their RNA vaccines, the composition of lipid nanoparticles, and why exactly these two vaccines require so different temperatures for keeping. My very best wishes (talk) 03:14, 1 December 2020 (UTC)

It will be interesting to see if the FDA publish this - Moderna are very protective over their lipid system (Moderna’s Mysterious Coronavirus Vaccine Delivery System), but it is hard to see how they could approve a vaccine for such large distribution (and likely no peer review), without such disclosure. 109.255.90.188 (talk) 10:39, 1 December 2020 (UTC)

I have moved your edit to the body until we know what happens here - have been looking for refs on what happens to mRNA that was encapsulated in lipids and nothing so far. There doesn't seem to be any timeline/information on any interim peer review of the newest mRNA vaccines (which is not optimal given yesterday's EUA in the UK). It is hard to push the article much further until we have such data imho? 109.255.90.188 (talk) 10:56, 3 December 2020 (UTC)

[3] (edit summary) - I presume RNA is no longer coated within the cell - as the Figure on this page shows. It should not be coated to be able to translate. But of course we need some published data about it. My very best wishes (talk) 16:20, 3 December 2020 (UTC)

Karolinska Institutet

• Various new editor accounts (could be the same person) keep pasting the following (in various versions) into the History section:

Use of RNA as a tool for vaccination was first published using mouse models by Berglund and Liljeström at Karolinska Institutet back in 1994 and 1998.

None of the references in the history section reference the Karolinska Institutet or Berglund and Liljeström? Even the Three decades of messenger RNA vaccine development, just published last year in Nano Today? Perhaps the editor(s) in question could provide independent evidence on this from a non WP:PRIMARY source. 109.255.90.188 (talk) 10:16, 2 December 2020 (UTC)

• I have moved this content to the talk page that was inserted by User:Pberglundvax:

Use of RNA as a vaccination tool for generation of antibody responses in vivo was first published by the Swedish scientists Berglund and Liljeström at Karolinska Institutet in 1994. NIH researchers Nicholas Restifo and Wolfgang Leitner in 1999 wrote about this work that "A single intramuscular injection of a self-replicating RNA elicited antigen-specific antibody and CD8+ T cell responses". This technology resulted in significant investments by pharmaceutical companies including Novartis Vaccines and Diagnostics, later acquired by GlaxoSmithKline, who under the leadership of Dr. Jeffrey Ulmer, one of the inventors of Plasmid DNA vaccines, spearheaded the industrial development of RNA vaccines based on self-amplifying mRNA.

I have read through the attached references (one is behind a paywall that I cannot access), and cannot find a reference to Berglund and Liljeström as being important in the history of mRNA vaccines, and in particular not in this important peer-reviewed 2019 article on the history of mRNA vaccines: Three decades of messenger RNA vaccine development. You cannot use WP:PRIMARY references to make statements that Berglund and Liljeström are important in mRNA vaccines, you MUST have reliable, quality, independent secondary sources (ideally ones discussing the history of mRNA vaccines as used in the article) (per WP:42) that support your statements. Otherwise, they will be taken out. 109.255.90.188 (talk) 11:45, 6 December 2020 (UTC)

• User 109.255.90.188 keeps removing any references to the seminal works on RNA vaccines that began in the early 90s, including the first study of the use for RNA as a vaccination too to induce antibody responses. This work was quoted in numerous early peer-reviewed review articles, including "Messenger RNA-based Vaccines" by Pascolo in 2004 (reference added). The paper from 1994 is indeed referenced in the 2019 article Three decades of messenger RNA vaccine development, see the graphical history figure.

What you have now added is now more consistent with Three decades of messenger RNA vaccine development, thanks. 109.255.90.188 (talk) 10:44, 7 December 2020 (UTC)

Thanks for pushing this in the right direction. — Preceding unsigned comment added by Pberglundvax (talk • contribs) 20:28, 7 December 2020 (UTC)

You are welcome, and thanks for responding to the requests for amendment. 109.255.90.188 (talk) 01:00, 9 December 2020 (UTC)

References

Article focus is skewed

The focus of this article is oddly skewed. The title says it's an article about RNA vaccines, but the actual article jumps directly to analysis of COVID-19 vaccines.

Either the article should be renamed (perhap "RNA Vaccines for COVID-19"), or else the general discussion of RNA vaccines (currently at the very end of the article, in the "history" section) should be at the front, not the end.

I moved one general section up to the beginning, so that there's some discussion of mRNA vaccines before the article jumps directly to COVID-19, but the article really should be refocussed. Skepticalgiraffe (talk) 13:55, 14 December 2020 (UTC)

The article is in bad shape still (discussed at WT:MED#Scary vaccines), but I think we do need an article on RNA vaccines so the solution is probably to add more material on that topic in general. Of course, it may turn out for the next few years the preponderance of sourcing for RNA vaccines is COVID-related anyway ... Alexbrn (talk) 14:05, 14 December 2020 (UTC)

Sloppy edit on 11 December 2020 that incorrectly summarized key point from cited source

I'm referring to this edit on 11 December 2020 by User:SandyGeorgia.

The previous text was mostly accurate in conveying the key point of the Stat article: that while still at Stanford, Dr. Rossi read Dr. Kariko's paper in 2005, recognized it was groundbreaking work, and looking back fifteen years later with the advantage of hindsight in 2020, said that it was worthy of a Nobel Prize in Chemistry. Anyone with basic training in close reading can immediately discern that from the face of the Stat article (specifically, the clause "he now says"). User:SandyGeorgia completely mangled that by implying that Dr. Rossi presciently arrived at that second conclusion in 2005. Any objections before I clean up this mess? --Coolcaesar (talk) 21:36, 14 December 2020 (UTC)

I haven't looked at the edit, but I object to your tone. Please asumme good faith and stop this personal attack. It's not a good look. Graham Beards (talk) 21:44, 14 December 2020 (UTC)

You might also want to read WP:TPYES and WP:TPNO, and remove my name from the section heading. Yes, I object to you cleaning up what you call a "mess" and suggest that you leave that to another editor on this page-- there are plenty of them who understand what is and is not excess detail and off-topic for this article. SandyGeorgia (Talk) 21:49, 14 December 2020 (UTC)

It's neither excessive detail nor off-topic to convey an accurate distinction between what Dr. Rossi thought in 2005 versus what he thought in 2020. In 2005, he recognized Dr. Kariko's work to be groundbreaking; in 2020, "he now says" (to quote from the cited article) that she deserves the Nobel Prize in Chemistry. As opposed to what you actually wrote on 11 December 2020, which implies he thought of both points in 2005 (in other words, your edit makes him sound incredibly pompous by being so prescient as to be able to foresee 15 years in advance that it was Nobel Prize-worthy work), and which is not what the Stat article says. It should be obvious at this point that I'm trying to do you a favor--before Dr. Rossi or someone close to him sees this article.

Look, if you didn't take the time to fully cross-check your edits against the contents of the cited sources when you edited this article, that's okay. You don't need to get so defensive about it. We all screw up sometimes. I've made my fair share of bad edits on WP. But if you really do not understand that you materially misstated the contents of the cited source, then that's a problem. Whenever you write about statements by living people, whether on WP or elsewhere, it's extremely important that you accurately summarize or restate what they actually said. It looks really bad to stuff words into their mouth. --Coolcaesar (talk) 22:33, 14 December 2020 (UTC)

The bigger question, on this particular article, is why we care what one individual's speculative opinion was about another individual. Other than that, when you approach a talk page with such a lack of AGF, I hope you understand that I am disinclined to engage further, but leave instead the sorting to someone uninvolved. Have you read WP:COI? Because this all seems rather related to the companies involved and more appropriate to those articles.

By the way, the article before I trimmed the off-topic content said: "In 2005, Harvard stem cell biologist Derrick Rossi read their paper, which he recognized as "groundbreaking", and for which he told Stat, Karikó and Weissman deserve the Nobel Prize in Chemistry." None of the distinction you say was there was actually there, when I trimmed the off-topic that looked like promotional content about the companies. You may find that approaching editing without impugning others will yield a faster result. Using the format: the article now says X, I would like for it to say Y is helpful. SandyGeorgia (Talk) 23:22, 14 December 2020 (UTC)

Just figured this out. That sentence was inserted in this edit by anonymous editor 109.255.90.188 on 30 November 2020. Traceroute reveals that's an IP address on a Virgin Media network in Ireland.

To me, the distinction was implicit in that the sentence was citing a 2020 Stat article (and was thereby implying that Dr. Rossi was commenting to Stat in 2020), but I personally would have not worded the distinction in that fashion because it's so easy to miss it that way (as apparently occurred here). It looks like 109.255.90.188 may be a non-native English speaker. In hindsight, I was able to pick up the distinction only because I read very widely, and have seen other non-native English speakers actually make that same error of burying the thing distinguished against in a footnote citation (they do it in other WP articles all the time). As a native English speaker, I would simply state the distinction clearly without assuming that the reader will infer it from the attached footnote.

So that's why I got so irritated earlier and I apologize. I thought you had missed something really obvious and perhaps it wasn't so obvious. --Coolcaesar (talk) 04:12, 15 December 2020 (UTC)

Thank you for the apology; appreciated and accepted. I make more stupid typos and editing errors than the average bear, and am happy to admit it, but just didn't quite see what had upset you so :) I am still concerned that we are giving undue weight to opinions in that whole section, which is why I only worked on trimming it, not even attempting to write it to a higher standard. Since I then posted to WT:MED for review, I actually expected someone to cut most of that. I would be happier cutting even more of the company-specific content or moving it to the company articles, but please do repair what is left there now as you see fit. Regards, SandyGeorgia (Talk) 04:21, 15 December 2020 (UTC)

Adverse Effects and Risks

This section had inline text

"References need to be added that discuss the unintended immune reactions and their frequencies. References need to be added that discuss all risks and adverse effects of RNA vaccines and their delivery systems."

(I'm about to replace that with an appropriate template, but the template needs a talk page section to refer to.) Lavateraguy (talk) 07:22, 18 April 2020 (UTC)

I replaced the phrase "should be avoided" with "needs to be circumvented" wrt the evolved mechanism to prevent incorporation of foreign nucleic acids. Evolution cannot be avoided, but can be circumvented.

Elsewhere, "lipid nanoparticles" are the only mention of a means to get around the extreme lability of naked RNA molecules when introduced at the cellular level. This is the aspect of RNA vaccines that, as a molecular biologist, I have been asked about and can't explain properly. Smcewincarr

Much of this section references outdated secondary sources (i.e. old articles in Science magazine). For example, hepatotoxicity is mentioned, based on an article in Science magazine from 2017, which is itself based on older nanoparticle technology. This whole section is fairly speculative. — Preceding unsigned comment added by Mcmastc1 (talk • contribs) 04:35, 9 December 2020 (UTC)

@Mcmastc1: Agreed. I have raised this at WT:MED#Scary vaccines. Alexbrn (talk) 10:34, 9 December 2020 (UTC)

MEDRS

I'm very concerned about the addition of biomedical claims not supported by WP:MEDRS-compliant sources, especially as this article is subject to general sanctions. For avoidance of doubt, I'm prepared to issue sanctions against any editor who is aware of the general sanctions and adds biomedical content that isn't supported by MEDRS sources. --RexxS (talk) 17:09, 9 December 2020 (UTC)

I'm disappointed to see that pre-clinical speculation about autoimmunity from a 2018 review article has resurfaced at the top of this section. This whole section is hand-picked speculation. Mcmastc1 (talk) 03:47, 22 December 2020 (UTC)

Mcmastc1. I'm trimmed the very worst. What specifically is bothering you in what remains? I don't like the look of that news (?) piece from Science either. Alexbrn (talk) 06:01, 22 December 2020 (UTC)

Changing names

Iztwoz I don't agree with obscuring the INN names here. SandyGeorgia (Talk) 00:13, 22 December 2020 (UTC)

I tend to take the side of the general reader who will know them by their common names. Would it be acceptable to include each INN name in brackets?--Iztwoz (talk) 08:36, 22 December 2020 (UTC)

MEDRS compliant

If there was ever a time to adhere to MEDRS compliancy this is it! There is so much conspiracy theory circulating seems we should be including only content that adheres in the strictest way possible to our own protections against such stuff. Just sayin'. Littleolive oil (talk) 20:41, 22 December 2020 (UTC)

Clarifying the "mechanism" section

Thank you to everybody for putting up with my questions and my clarify tags. Couple of follow up questions.

• When a dendritic cell uses phagocytosis on, say, a random virus in the human, do its ribosomes start producing viral antigens? Trying to figure out if this is something special to RNA vaccines, or something that these cells always do when they consume something containing mRNA.

No. As the article says, the vaccine mRNA is modified to ensure it is translated. And, viruses are too small to be "randomly" phagocytosed; they have to be coated with antibody first. Also, only a few viruses have positive sense RNA in any case. Lastly, mRNA is transient and does not linger in cells.You need to read around this subject more. Start with mRNA. Graham Beards (talk) 08:26, 24 December 2020 (UTC)

• Somebody added an awesome diagram. In it, there is a fork, and the entire left side is a workflow for non-dendritic cells. Does the RNA vaccine affect more cells than just dendritic cells? edit: Oh, I think I get it now, I guess "any cell" includes dendritic cells.

–Novem Linguae (talk) 08:06, 24 December 2020 (UTC)

Plenty of good sources on mRNA vaccines

See here

https://www.nature.com/articles/nrd.2017.243.pdf

Given all the anti-vaxx hysteria at the minute, this article needs to get sorted PDQ.

I came to wiki to find information because a family member has been told mRNA vaccines will lead to huge health problems in 2-3 yrs for those having it for Covid. There are numerous anti-mRNA videos on the web peddling horror stories. — Preceding unsigned comment added by 2A00:23C4:2682:3C00:FC6D:518E:D13F:9FF5 (talk) 13:56, 2 January 2021 (UTC)

In general, that kind of stuff is found more at Misinformation related to the COVID-19 pandemic, although the RNA vaccine misinformation is also dealt with here in the Society and Culture section. Alexbrn (talk) 14:00, 2 January 2021 (UTC)

Last paragraph of introduction is of low quality

The last paragraph of introduction is too biasing and tends to be subjective. The arguments are social-media level. It triggers doubts more than it answers. B.yanis (talk) 13:15, 5 January 2021 (UTC)

Misinformation is a minor but important aspect of this vaccine, as covered by RS. A mention is WP:DUE. Alexbrn (talk) 13:21, 5 January 2021 (UTC)

I agree with Alex but would be even stronger: Misinformation and identifying it per the research we have is a critical aspect of understanding this vaccine in the midst of a world wide pandemic. Littleolive oil (talk) 19:40, 5 January 2021 (UTC)

The advantages ...

Quote from article: "The advantages of RNA vaccines over traditional protein vaccines are superior design and production speed, lower cost of production, and the induction of both cellular as well as humoral immunity." Great. Then why wasn't it produced before the Corona-era? — Preceding unsigned comment added by Koitus~nlwiki (talk • contribs) 16:40, 8 January 2021 (UTC)

The "History" section should answer that question but does not. It mentions "poor results" up until 2020 and "serious side-effects". It should also mention the much better results in 2020. Tozinameran, for example, says, Trials began in April 2020; by November, the vaccine had been tested on more than 40,000 people.[21] An interim analysis of study data showed a potential efficacy of over 90% in preventing infection within seven days of a second dose.[17][18] The most common side effects include mild to moderate pain at the injection site, fatigue, and headache.[22][23] As of December 2020, reports of serious side effects, such as allergic reactions, have been very rare,[a] and no long-term complications have been reported.[25] mRNA-1273 does not have a summary of test results, but should have.

Also, I doubt that Operation Warp Speed had even "indirectly" funded the Pfizer/BioNTech vaccine. The source given does not mention that. --Hob Gadling (talk) 12:36, 9 January 2021 (UTC)

Issue with the article claiming RNA and mRNA vaccines are the same

RNA vaccine is not the same as mRNA (messenger RNA) vaccine as not all RNA is messenger RNA although the current vaccines use mRNA but its not the same as RNA and there is a difference in effectiveness as mRNA is more effective then RNA and that is why the first vaccines use mRNA not regular RNA and why the regular RNA vaccines failed — Preceding unsigned comment added by 71.169.166.208 (talk) 11:19, 23 January 2021 (UTC)

They are the same. See this Nature Research article. Graham Beards (talk) 14:13, 24 January 2021 (UTC)

Efficacy section not balanced

The "Efficacy" section reads as very skeptical and mostly consists of opinions expressing doubts about the COVID vaccines. I would think the section should start with known information about efficacy: successful trials of the COVID vaccines and whatever else is known about the efficacy of other RNA vaccines. Then to balance, add some positive quotes/opinions along with the skepticism that is currently represented. Sgtbilko99 (talk) 19:53, 8 December 2020 (UTC)

There was more text in this section but it seems to have been edited out and what remains is not that coherent. Ultimately, we have press statements from the companies, but we still await published data from the regulators (which is unusual but these are unusual times), and of course, the results have not been able to be peer-reviewed (which is what we really need, but I suspect something will happen here in the near-term given the scale of the distribution - even if it is just provisional). However, I will come back tomorrow to this to fix back. 109.255.90.188 (talk) 01:00, 9 December 2020 (UTC)

The efficacy of 90-95% is not backed up. The New Scientist cite note only mentions the 90% figure, and even that is not referenced for a source. What is 90% of what, for example? Did they try to infect vaccinated people with actual COVID-19? — Preceding unsigned comment added by 51.9.80.20 (talk) 12:51, 18 January 2021 (UTC)

Greetings from Belgium - as you know we were a region with a lot of infected people and it is a.o. in Belgium that a lot of the testing and production of the vaccines were done because we have a big pharma research sector here. So there was no need to infect people who participated in the trials on purpose with COVID-19 - part would have it, part would get infected during the trial. It is Prof. dr. Isabel Leroux-Roels who is one of the persons responsible for all these trial studies. Here you can listen to her on flemish TV - https://www.vrt.be/vrtnws/nl/2020/06/11/honderden-kandidaten-om-proefpersoon-te-zijn-voor-coronavaccin-i/ , cheers, SvenAERTS (talk) 09:39, 2 February 2021 (UTC)

"Before the COVID-19 pandemic, no mRNA drug or vaccine was licensed for use in humans." ?!

This is a quote from the article. Can anybody help check that as it is a big reason here in the dutch speaking region why people do not want to get vaccinated. Enfin, here the claim circulates that mRNA vaccines are still experimental and new, whereas "The use of RNA vaccines goes back to the early 1990s." Thy and greetings from Brussels :), SvenAERTS (talk) 09:50, 2 February 2021 (UTC)

Go read the Stat article already cited in the article as the basis for that statement (the footnote is attached to the sentence after the one you just quoted). The article specifically says: "Although relatively easy and quick to produce compared to traditional vaccine-making, no mRNA vaccine or drug has ever won approval." That article explains most of the difficulties encountered in bringing mRNA vaccines and drugs to market. Quartz has published its own article which explains the other major difficulty involved: developing an adequate delivery system for mRNA. --Coolcaesar (talk) 15:56, 2 February 2021 (UTC)

Also, Derek Lowe at Science Translational Medicine has just published a blog post which explains at length and in plain English why it is so hard to scale up the manufacturing of mRNA vaccines. --Coolcaesar (talk) 17:33, 3 February 2021 (UTC)

"traditional protein vaccines"

Is this referring to https://en.wikipedia.org/wiki/Subunit_vaccine ? Shouldn't "traditional" be either https://en.wikipedia.org/wiki/Attenuated_vaccine or https://en.wikipedia.org/wiki/Inactivated_vaccine as these have been around the longest? I would add a link but not sure which one is being referenced (maybe all of the above?) --Melarish (talk) 02:39, 10 February 2021 (UTC)

Semi-protected edit request on 18 March 2021

NOT a VACCINE ......Gene Therapy . A vaccine has some of the attenuated live particles within the vaccine to provoke an Immune response . 199.247.74.137 (talk) 17:46, 18 March 2021 (UTC)

WP:COMMONNAME applies. — Preceding unsigned comment added by ScottishFinnishRadish (talk • contribs)

Speed at which vaccine was produced

I remember the media crediting Trump for speeding up the process for this vaccine by eliminating regulatory barriers, etc., but I failed to see any mention of that historic action in the article. History would be more accurate were there a mention of this fact when discussing how the vaccine was ready and available so quickly. Facts are facts and matter! 74.219.95.99 (talk) 18:35, 17 March 2021 (UTC)

...except that RNA vaccines for Covid-19 were produced quickly in multiple countries, most of which Trump had no control over. It isn't news when politicians assign anything good to their policies and anything bad to their opponents policies. --Guy Macon (talk) 10:33, 28 April 2021 (UTC)

Presenting whole spikes

The article contains the phrase "display spikes on their surfaces". The source only talks about presenting fragments of spikes. Can whole spikes be presented? Wain2 (talk) 08:34, 14 May 2021 (UTC)

To add confusion, there's an explanation by Moderna from 2017 with an image showing antigens exiting a cell or sticking to a cell surface without being broken down and without involving MHC. Are viral antigens in general able to do that, but spikes specifically aren't? Wain2 (talk) 09:35, 14 May 2021 (UTC)

Add paragraph about host cells dying?

If I'm understanding it correctly, RNA vaccines inject mRNA, which then goes into human cells. The human cells then start producing antigen proteins and put these on their cell membrane. I imagine this causes the human's antibodies to target these vaccinated human cells and kill them. In other words, many human cells will be killed.

This article could use a paragraph specifying how many human cells are killed by a typical RNA vaccine, and whether this presents any danger to the human. Or if I am misunderstanding this completely, a sentence somewhere mentioning that this does not happen and it actually works X way would be helpful. –Novem Linguae (talk) 16:17, 15 December 2020 (UTC)

No, you are mistaken. See Antigen presentation. Graham Beards (talk) 18:49, 15 December 2020 (UTC)

Thanks for clarifying. I made a small edit to include this info. –Novem Linguae (talk) 03:42, 16 December 2020 (UTC)

Graham Beards, are we 100% sure the vaccine doesn't cause the host cells to die? I found two pieces of information that may suggest it does.

From major histocompatibility complex wikipedia article: The presentation of pathogen-derived proteins results in the elimination of the infected cell by the immune system.

From an article I googled [4]: The finding that these vaccines cause their target cells to die by apoptosis is an added safety feature that also seems to increase efficacy. –Novem Linguae (talk) 05:35, 17 December 2020 (UTC)

That's not a reliable source. 06:08, 17 December 2020 (UTC)

You sound like you understand how it works. Feel free to share details, and then we can adjust the articles to make those details clear. Right now, the articles appear to contradict each other. (Example: that MHC article saying that the host cells die, but the RNA vaccine article saying they don't). –Novem Linguae (talk) 06:35, 17 December 2020 (UTC)

There are dangers in oversimplification. I suggest you read Macrophage. Pus is full of spent (dead) leukocytes. Host cells, particularly those of the immune system, die all the time - vaccine or no vaccine. I think the direction your heading is tantamount to scaremongering. Graham Beards (talk) 06:59, 17 December 2020 (UTC)

Hey Iztwoz. Thanks for your edits today and for adding good info to the article that satisfied my clarify tag. You seem pretty knowledgeable about this topic, maybe you know the answer to the question I asked above. The question is, "what happens to human host cells that take up these mRNA molecules"? When the human host cells express these viral proteins, are they in any way attacked by the innate immune system, or later on by the adaptive immune system's antibodies? I feel this is a question that a layman article reader such as myself would have when reading the article, and that it is not really covered in the article yet. Thank you. –Novem Linguae (talk) 15:22, 20 December 2020 (UTC)

Really, I know nothing. All I can do is read relevant material, try to understand it and relay it in hopefully a comprehensible way.--Iztwoz (talk) 17:08, 20 December 2020 (UTC)

Graham Beards and soupvector are the relevant topic experts. SandyGeorgia (Talk) 17:45, 20 December 2020 (UTC)

I have already answered the question. Graham Beards (talk) 20:08, 20 December 2020 (UTC)

Graham Beards, Sounds like you think cells targeted by RNA vaccines are not in any way harmed by either innate or adaptive immune system. But I still do not understand why. Do you know and would you be willing to elaborate a bit? I did read portions of the articles you linked, and this is still not clear to me. My layman, simple understanding of how this all works is that the immune system will attack cells that have an antigen, yet somehow these are not attacked? Again, the following quote from the MHC article seems to contradict the idea that host cells are not harmed. The presentation of pathogen-derived proteins results in the elimination of the infected cell by the immune system.

Also, I'm not sure what was up with your "scaremonger" comment. Asking good faith questions on a talk page does not seem like scaremongering to me. But that is why I didn't choose to follow up/ping you about this. But you're back, so I will try again to communicate and get understanding of this topic. –Novem Linguae (talk) 21:28, 20 December 2020 (UTC)

Novem, I am sure that if Graham had a free moment to answer your question in greater depth, he would. (I understood his answer.) I hope you understand what it is to be pulled out of retirement and pressed to the front lines of this pandemic in the UK, as is Graham. Please be patient; I, for one, appreciate every word he finds the time to type here. SandyGeorgia (Talk) 21:39, 20 December 2020 (UTC)

SandyGeorgia, I'm happy to conserve his time if you want to take a stab at answering. Or if this issue is too sensitive, we can just drop it completely. –Novem Linguae (talk) 22:02, 20 December 2020 (UTC)

I don't find it sensitive at all, but I cannot expand beyond what Graham has already stated (pus is full of spent (dead) leukocytes. Host cells, particularly those of the immune system, die all the time - vaccine or no vaccine). SandyGeorgia (Talk) 22:06, 20 December 2020 (UTC)

Oh. Are you saying the mRNA only targets/goes into a certain kind of immune cell? I assumed it was all cells, or a non immune cell. –Novem Linguae (talk) 22:15, 20 December 2020 (UTC)

The vaccine is picked up by Dendritic cell which are macrophages. It doesn't "target" any cells. There is a good review article here. [5]. Graham Beards (talk) 08:39, 21 December 2020 (UTC)

This is from CDC

"COVID-19 mRNA vaccines are given in the upper arm muscle. Once the instructions (mRNA) are inside the immune cells, the cells use them to make the protein piece. After the protein piece is made, the cell breaks down the instructions and gets rid of them. Next, the cell displays the protein piece on its surface. Our immune systems recognize that the protein doesn’t belong there and begin building an immune response and making antibodies, like what happens in natural infection against COVID-19." (My bolding)

The DC cells eventually die probably by apoptosis, but these cells along with thousands of other cells of the immune system are dying everyday: vaccine or no vaccine. I think the problem we seem to have here is that the article, in an attempt to be layperson friendly, is just saying cells. Now, clearly we don't mean hair cells, skin, or cells that make toe nails, but perhaps we should be more specific. Graham Beards (talk) 14:08, 21 December 2020 (UTC)

Thanks for the detailed reply. I think I get it now. I had a faulty assumption that the mRNA went into non-immune cells. Looks like the mRNA goes precisely into the exact immune cell that it needs to in order to start building adaptive immunity. Pretty clever, actually. Kudos to the developers of this technology platform.

The cell death part isn't even important now that my base assumption has been corrected, since DC's aren't "infected", per se. Rather, having and expressing antigens is normal for them, and nothing to be concerned about.

Some things to add to the article at this point might include "how does this technology platform target only dendritic cells?" Does this mRNA end up in all cells, but only dendritic cells express it on the cellular membrane? Does this mRNA only go into dendritic cells?

I'll read your Nature article and probably do a little more copy editing for clarity. Hopefully I can help polish away some of these layperson vs technical issues. Thanks for your time. –Novem Linguae (talk) 14:41, 21 December 2020 (UTC)

Below is a link where Bali Pulendran at Stanford says the vaccine does enter non-immune cells, but less efficiently. I assume it is the same as the DC cells, and not killed. Would be nice if the article could clarify, when the immune system sees spike proteins, how does it distinguish between infected cells it needs to kill versus vaccinated cells that it leaves alone? https://scopeblog.stanford.edu/2020/12/22/how-do-the-new-covid-19-vaccines-work 68.34.140.215 (talk) 03:46, 30 May 2021 (UTC)

Molecules are neutral entities, just sayin'

The article and probably several like it refer to mRNA as "molecules". Of course they are ions, but maybe there is no better term and efforts to be more precise would just confuse readers and ruin readaibility. --Smokefoot (talk) 21:42, 27 June 2021 (UTC)

Extended-confirmed-protected edit request on 28 June 2021

Why was the history of the discovery removed? It had sources and now the article is misinformation Fluridil-god (talk) 19:46, 28 June 2021 (UTC)  Not done sources still used. Alexbrn (talk) 19:57, 28 June 2021 (UTC)

Epitranscriptome studies need to be talked about

The transcripts for protein spike of long non-coding mRNA needs to be added to the page. It’s unable to be edited, but the research is clear that general population using mRNA tech is not as efficacious for transcription as promoted. Chemical modifications when translations are doing the one job of addressing the reason of design, but that same message (transcript) is being sent elsewhere.

More info: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713356/

KG90Learns (talk) 02:06, 29 June 2021 (UTC)

Extended-confirmed-protected edit request on 4 July 2021

The history section needs to be much improved. RNA vaccines date back at least to the 1970s. Venneman, et al. in Immunogenicity of Ribonucleic Acid Preparations Obtained from Salmonella typhimurium. Infect Immun. 1970 Jun; 1(6): 574–582 used whole cell purified RNA from Salmonella typhimurium to immunize mice and showed protection against infection upon challenge with Salmonella. Likewise, ribosomal fraction RNA vaccines date back to at least the 1960s. 134.56.31.244 (talk) 03:50, 4 July 2021 (UTC)

 Not done Would need secondary sources saying this was so. Alexbrn (talk) 03:55, 4 July 2021 (UTC)

Try to find the sources. I hear Malone is still visible in the 1989 references and this is giving ammunition to the anti-vax crowd. It's better to be flexible if necessary, don't you think? 46.10.181.145 (talk) 08:57, 4 July 2021 (UTC)

Not really, WP:V is a core policy for a reason. Alexbrn (talk) 09:03, 4 July 2021 (UTC)

Extended-confirmed-protected edit request on 4 July 2021 (2)

No mention of Dr Robert Malone who invented the technology and holds the patents.

Please rectify or clarify the discrepancy. 37.155.61.207 (talk) 17:58, 4 July 2021 (UTC)

Please read the rest of this page to see why we will not be doing anything as a result of this request. -Roxy the grumpy dog. wooF 18:02, 4 July 2021 (UTC)

Jon Wolff unique contribution?

Just wondering- why name Jon Wolff specifically, as opposed to just using 'researchers at the University...' or naming all of the involved scientists? The first citation used for this uses 'Wolff et al.', (which then cites the paper attributed to "J.A. Wolff, R.W. Malone, P. Williams, W. Chong, G. Acsadi, A. Jani") and the second is a citation directly to the paper.

Were there any contributions made uniquely by Jon Wolff to give him higher naming priority? 2601:249:8180:28D0:686E:C59D:A30F:2945 (talk) 17:38, 4 July 2021 (UTC)

The first named author in multiple author papers is normally the corresponding author. -Roxy the grumpy dog. wooF 18:04, 4 July 2021 (UTC)

Is the Wikipedia article on RNA vaccines an attempt to correspond to the author of that paper? Isn't the purpose, at least in part, to properly credit the discovers and inventors? — Preceding unsigned comment added by 105.160.36.116 (talk • contribs)

Malone deleted?

The following discussion is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

---

This is an obscene elephant in the living-room. He used to be in this article, but wacko revisionists ghosted him after June 12th, 2021 when he reported the systemic transport problem identified through the Japan FOIPOP and Dr Bridle. Kashmiri simply erased this petition to include Malone as the DOCUMENTED inventor of mRNA as if the world doesn't already know. See the real history at https://www.rwmalonemd.com/mrna-vaccine-inventor — Preceding unsigned comment added by 24.138.33.183 (talk • contribs) 10:33, 6 July 2021 (UTC)

There are at least two discussions about the same topic above. Adding the third one here is of no help. — kashmīrī ^TALK 10:40, 6 July 2021 (UTC)

Yes it does. You keep deleting the rationale and his documented academic history. https://www.rwmalonemd.com/mrna-vaccine-inventor

His prior art is a fact of scholarship. — Preceding unsigned comment added by 24.138.33.183 (talk • contribs)

Between 2017 and recently an account has existed purely, it seems, for the purposes of adding Malone's name to multiple articles on Wikipedia.[6] On 8 June this year the account added Malone's name to this article.[7] Such additions were not backed by the sources cited; in fact no reputable source identifies Malone as the "inventor of RNA vaccines", or even as a significant figure. The account was blocked for self-promotion/spam and the article returned to its longstanding form and improved in other ways. Meanwhile, on social media and in the scummier parts of the web, a lie has been spread that "longstanding" information on Wikipedia was scrubbed. Some people have been suckered in by this. Alexbrn (talk) 10:44, 6 July 2021 (UTC)

It is a published fact. In as much you accuse Malone of self-promotion, you are anti-promoting Malone. Facts are facts. — Preceding unsigned comment added by 24.138.33.183 (talk) 10:49, 6 July 2021 (UTC)

It is only claimed by him. Nobody agrees. To show otherwise, produce an independent, reliable, source. Alexbrn (talk) 10:55, 6 July 2021 (UTC)

His laboratory notebook, was signed August 29, 1989. Signed and dated notebooks are the legal standard for priority.

Wikipedia reflects accepted knowledge in reliable, published, sources. If you want to engage in overturning that, go somewhere else to do it. Without such sources, nothing can change. Alexbrn (talk) 11:03, 6 July 2021 (UTC)

US law is the standard. Not your opinion. Signed and dated notebooks are the legal standard for priority. First to Invent as a legal principle was the standard for priority date until that was changed under Obama to First to File. All US courts recognize contemporaneous notes signed by the author as factual evidence for priority date. See https://en.wikipedia.org/wiki/First_to_file_and_first_to_invent

"The standard" is what is published in reliable sources. An enyclopedia is just a summary of such sources. If you're here to WP:RGW you're wasting your time. Alexbrn (talk) 11:09, 6 July 2021 (UTC)

The most reliable source in US Patent Law is the inventor's signed and dated laboratory notebook. There is nothing more reliable than that. You wont even look at the jpeg. This is the exact problem that has lit up the news. Wiki editors ignored glaring published facts. And yes, the notebook has been published in the USPTO in the "file wrapper" for all his subsequent USPTO submission because patent law required him to do so. All the court documents are a mater of record. Your dislike of Malone is showing. It is getting kind of silly.

The discussion above is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

Here is wikipedia's article on the relevance of the laboratory notebooks reliable evidence. https://en.wikipedia.org/wiki/Inventor%27s_notebook — Preceding unsigned comment added by 24.138.33.183 (talk) 11:41, 6 July 2021 (UTC)

efficacy

this sentence "This fragility of the mRNA molecule is a hurdle to the efficacy of any mRNA vaccine due to bulk disintegration before it enters the cells, which could lead people to believe, and act as if they are immune when they are not" is only supported by a journalistic source from Nov 2020 which is a long time ago and is pure speculation, mashing up the stability of mRNA with efficacy and people's behavior. None of this is supported by any MEDRS and the sentence should be removed. --hroest 15:14, 6 July 2021 (UTC)

Removed, thanks. Whoever wrote it, has misunderstood the Cambridge Uni source. mRNA fragility refers only to naked mRNA, that's why no current vaccine uses naked mRNA. — kashmīrī ^TALK 20:37, 8 July 2021 (UTC)