The new mRNA covid vaccines are all offering really high effectiveness. Much more effective than any flu vaccine, for example. Are they effective because they’re mRNA based, or is it just luck that the vaccines for this particular illness are this effective? If it is because they’re mRNA vaccines, could we use the same method to make more effective flu vaccines?
There were several other mRNA vaccines that were worked on before now, but they all failed. If they’ve ironed out whatever issues caused the previous vaccines to fail, is it possible that we’ll see other vaccines soon that use mRNA? I mean, does this new technique succeeding potentially open the door to more effective and safer Lyme disease (for humans - the last human LD vaccine was discontinued due to severe side effects), malaria, Zika, or even adenovirus or norovirus vaccines and/or a vaccine against some of the 200 rhinoviruses that cause the common cold?
In short, just how excited should we be about the mRNA breakthrough(s)?
I wouldn’t say that mRNA vaccines previous to this one all failed, but it was the case of ‘if it ain’t broke, don’t fix it’. Conventional vaccines have a good long term track record, coming out with an entirely new class of vaccines without that long term history is a hard regulatory battle. It just was not economically feasible to get it approved to market. But it was developed and was developed because it had great potential for fast development but also when a major pandemic came along (which was always expected at some time), a fast track to market would open (and it happened everywhere in the developed world, the US version was named operation warp speed, but other countries also fast tracked it without having to give it a fancy name) - we just came up with a fancy name for it, and some got it to their population faster then us. So they knew if and when a pandemic came up they can use this to develop and thus open the door to mRNA.
I’m having trouble finding information about where previous (recent) mRNA vaccine research failed, or even if it did, but I suspect the lack of success previously is due to a combination of these factors:
Vaccine research is underfunded due to low profitability.
Some of the key solutions used in the new COVID-vaccines are relatively new, so other vaccines utilizing them, which aren’t being rushed through and funded like this COVID push, are still moving slowly through the regular glacial pipeline, or have been shelved due to uncertain future profitability.
Specifically in comparison to the flu vaccine: The flu vaccine is created ahead of the seasonal epidemic by guessing which strain(s) of the flu virus will dominate that year. Some years it is highly effective. When it isn’t it’s more that people are vaccinated against a “cousin” of the dominant virus, than it is that that vaccine is inefficient against the specific virus it was designed to work against.
And we might still get smacked in the face by COVID pulling the flu move on us and have substrains the vaccine is ineffective against cause reemergence and new surges. Fingers crossed that won’t happen.
I have not followed vaccine research until the mRNA vaccines. But have previous vaccines ever been developed and deployed that used the cell marker method? I am referring to the technique in the mRNA vaccine where the vaccine consists of the molecular piece used by the virus to enter the host cell. Essentially the key that allows it to get inside the host cell. By targeting this one piece of the COVID virus, the vaccine doesn’t care about the mutation of the virus, as long as the virus has that key it will trigger an immune response. And if the key mutates, then it is likely (but not impossible) that the virus will become less infectious. Sounds like a great idea. Has it been used before?
As to the OP, I am curious as well. Even more than how the vaccine works, the high speed development, testing, and approval process holds great promise for the future. Assuming there are no significant failures or negative consequences to the development and approval process for the mRNA vaccine, if we can use this model of vaccine development in the future we can make great improvements to public health.
If I correctly recall Moderna has been working on mRNA vaccines/treatments for the entirety of its existence as a company, and the covid vaccine is to date their only success.
ISTR that several of the companies currently producing mRNA COVID vaccines were already working on that sort of vaccine prior to COVID, and basically repurposed their existing research for COVID.
So sort of a lucky break, in that it’s not like they spun up a mRNA vaccine out of nothing, but rather had essentially figured it out with SARS and/or made very recent breakthroughs in vaccine research, and were able to adapt it to COVID extraordinarily quickly.
So ready were they to adapt the existing research, that in fact, that the Moderna vaccine was designed BEFORE there were confirmed cases in the US- not quite one year ago on January 13th.
Early on I read somewhere that Moderna (whose name means "something"RNA) had developed an RNA vaccine against ??? (maybe Ebola) but couldn’t afford to test it and that if they had they would have been able to hit the ground running. But the funding from Warp Speed made it all possible. Meantime, Pfizer was a huge company that could afford the testing didn’t get any direct funding (just a guarantee to sell 100 million doses).
I am slowly learning to search Youtube as often as Google. On the tube there are several great explanations of modern vs traditional vaccine development and production that clearly explain the how and why. My explanation above is mostly correct, but have a listen to the following for a better explanation:
I think it’s important to notice that vaccinating against cancer is a fairly new idea overall and that mRNA-treatments encounter a lot more issues than a vaccine does, because you generally have to use much larger doses.
That leaves the Zika vaccine, which isn’t so much an example of failed research as it is of incomplete research. To quote from the link you supplied:
Moderna’s initial candidate vaccine for Zika virus, for example, was well tolerated in people but failed to provoke much of an immune response. With funding from the US government, Moderna went back to the lab, optimized the vaccine sequence and developed another candidate that is, according to Zaks, “at least 20 times more potent” than the first-generation product in mice and monkey testing.
I would be cautiously optimistic about the potential that mRNA treatments offer, and skeptical about any specific claims of what they will actually do absent of clinical trial data.
One of the really desirable things about mRNA vaccines is that they can be highly targeted; the vaccine is literally just a string of messenger RNA which codes for the desired antigen protein and inserted into a lipid nanoparticle for delivery to cells that will then replicate and express the antigen for the immune system to develop a response. Because the mRNA contains only that specific protein(s), and they can be sequenced directly, making a novel mRNA vaccine or modifying one in response to mutation of a virus or bacteria is ‘easy’ (for generous values of ‘easy’).
In contrast, an active or attenuated virus vaccine is selected that expresses a protein similar to the desired antigen or has the necessary gene sequence inserted into its genome. In the adeonvirus-based SARS-CoV-2 vaccines, for instance, a sequence to produce the proteins necessary to make up the spike protein containing the receptor binding domain. The transcribes the DNA, produces its on mRNA, and produces the antigen that is presented as above.
In the case of the mRNA vaccine, the potential for any kind of cross-contamination with an unexpectedly interoperative virus is minimal. This has actually been a problem in the past; a significant percentage of early oral polio vaccines were contaminated with SV40 due to the rhesus monkey kidneys used to produce the vaccine. On the other hand, such vaccines have very limited persistence in the body; essentially, once the lipid nanoparticle enters the cell and delivers its mRNA package, it is done. Obtaining a more robust immune response may require one or more boosters; both of the mRNA vaccines for SARS-CoV-2 have a second booster shot in their protocol with a 21 or 28 day interval, but how good of a long term immunogenicity that will provide is still unknown. There was also some concern about potential reactions to the lipid nanoparticle early on but I haven’t seen anything recently and as far as I can tell the lipid is just a normal molecule that the body should be able to break down.
Active or attenuated viruses may have a greater degree of persistence and therefore require a smaller dosage, and furthermore the presence of a virus, even if not itself pathogenic in humans, may stimulate additional immune response. The Johnson & Johnson vaccine protocol only has a single shot, although again, the long term immunogenicity is an unknown. The active and attenuated viruses are also more robust than the lipid nanoparticle-containing mRNA vaccine, and thus, don’t require being stored and transported at cryogenic temperatures. This is a boon for the anyone dealing with the complex logistics of getting vaccines from production to arms even in industrialized nations, and absolutely crucial to get vaccines to developing countries.
One thing that should be pointed out is that in both the Pfizer and Moderna vaccine trials, antigen testing for infection was only performed on symptomatic people, while in the Oxford-AstraZenica trial that was run in the UK, all participants were repeatedly subject to antigen tests. Therefore, infected but asymptomatic subjects would show up as positives in the latter but not in the former. I don’t know if this statistically bridges the difference between the effectiveness of the mRNA vaccines versus the adenovirus-based O-AZ, but given an assumption of half of all infected people are asymptomatic you could reasonably reduce the effectiveness of the mRNA vaccines to somewhere closer to 85% to 90% (which is still quite good). All vaccines appear to have reduced morbidity substantially (no hospitalized patients in any of the trials except for a few allergic reactions which are a potential for any vaccine or medication trial) and have effectively eliminated pathogenic mortality in the study population. Hopefully that holds for later age populations as well.
Anyway, mRNA treatments have a lot of potential beyond vaccines, provided the stability and delivery issues are addressed but when it comes to the immune system and cellular metabolism there is still a lot of trial and error. Bringing a new treatment to market is often the work of a decade or more of research and clinical trials, and many fail, either because they lack the desired efficacy or because the company runs out of money to complete research even if the treatment itself has no safety issues. In theory, a robust mRNA vaccine infrastructure could pump out new vaccines in weeks of sequencing a new viral genome and identifying the target antigen, but you’d still have to run many months of safety and efficacy trials before a vaccine would be approved for broad use, and that isn’t going to change any time soon because the potential of a harmful vaccine would undermine vaccine campaigns and public health in general.
So what’s the advantage of introducing into the body the mRNA for a single specific protein, vs. introducing into the body that single specific protein itself?
The spike protein by itself floating around the bloodstream will probably elicit no immune response, or at most a transient response like exposure to an allergen. By encapsulating the mRNA in a lipid nanoparticle it ensures that it is absorbed into an antigen-presenting cell (APC) which activates the adaptive immune cell.
I have an interest in anifrolumab, a lupus drug which it’s backer hopes is a breakthrough. From the name, it’s a ~monoclonal antibody, but I’m unable to decode ~frolu~ or ~lu~ .
~u~ may mean human.
Anyway, I’m wondering if there is going to be an mRNA variant of the drug soon, which is why I was wondering what the mAb technology is: presumably if it’s a ~human~ technology, there’s less incentive to upgrade the drug to an mRNA version.
