The non-mRNA COVID-19 vaccines that targeted the entire virus rather than just the spike protein generally produced somewhat more durable immunity even after many mutations. In principle it might be possible to make mRNA vaccines that work in a similar way, so I don't think it's a fundamental weakness in the technology.
It's more that sars-cov-2 is just a nasty virus with exceptionally good skills at evading the immune system, not that mRNA vaccine tech doesn't work after a few months. From what I understand covid-19 can suppress the immune system response and replicate before your body can really detect or react to it. It's only if you have a recent supply of covid-19 spike protein antibodies floating around your blood, like if you were recently vaccinated/boosted, that your immune system can get a faster alarm and head start at clearing a real infection.
So really any vaccine mRNA or not that's targeting the spike protein is going to see similar waning efficacy against infection. We see this with the Johnson and Johnson and Astrazenica shots which don't use mRNA tech for example.
Not mRNA vaccines, COVID vaccines (all of them, doesn't matter the type). To be specific Coronaviruses are known not to produce lasting immunity, COVID is no exception.
They failed in their primary goal: Creating lasting immunity to this disease. They succeeded in a secondary goal: Reducing severity of infection.
The trouble with failing in the primary goal is that COVID is here forever.
I'm unfamiliar with anything in this line of research -- the Covid mRNA vaccines haven't provided longer-term immunity, but that's not at all due to the mRNA, but due to the nature of coronaviruses, how quickly they mutate and how many different mechanisms they have for cell entry. "Traditional" vaccines were actually performing worse for Covid19.
I'd be curious to read more about long-term immunity issues if you have some links?
They were wildly effective for a few months after being given. We don’t know how well they would continue to work in the absence of mutation.
But it’s worse than that: the revised vaccines appear to be nowhere near as effective even against strains closely related to those which they target. As a somewhat plausible mechanism, repeated doses have been shown to induce IgG4 production, which non-mRNA vaccines don’t seem to do.
Measles and Chickenpox are both airborne, although they’re not respiratory the way Covid is. But their respective vaccines are vastly more effective.
I’m not saying that I know, or have strong evidence, that mRNA vaccines are weak. But I do think it’s fair to say that we have no evidence that they can be comparably effective to earlier vaccine technologies.
Interestingly, the mRNA vaccines produce superior immunity compared to getting infected, due mainly to the two dose regimen. For similarly long-lasting natural immunity you'd probably need to get infected with covid twice.
The current vaccine is only 64% effective, but new safe and effective mRNA vaccines can be made on a very short timescale compared to other vaccines (as seen by the initial COVID-19 vaccines themselves).
The problem isn't having a vaccine available that's protective enough... it's getting enough holdouts to actually take it before another mutated variant takes over.
When mRNA vaccines were invented, I was told that it had the advantage that a mRNA vaccine can be easily modified so as to be effective against a mutated virus. Yet after so many mutations of covid, all we have is still the original version of covid mRNA vaccine. Why?
Not an expert, but couldn’t the mRNA vaccine target only part of the virus genome that’s stable across mutations/variants? That would give you a broad vaccine resistant to mutations
You're completely wrong about robustness against strains. Via mrna vaccine your body only learns how to target the spike proteins that (inadvertently) break off the cell membranes and travel throughout your body. On the other hand actually getting covid your body explores various vectors against the virus not just spike proteins.
For me the most convincing argument regarding safety is that mRNA vaccines essentially do the same thing that the virus does, just extremely limited in scope (producing just one protein instead of a bunch of them, and not reinfecting more cells).
So, even if producing the proteins turns out to be somewhat harmful long term, it cannot possibly be as harmful as the whole virus.
Assuming that covid infection is inevtable without a vaccine, we really have a choice between getting a little bit of mRNA injected into our cells, and a ton of mRNA injected.
No one in this thread knows anything about vaccines or infectious disease. Each organism is different and requires a detailed understanding to see what the potential for the vaccine is. You can't just take COVID-19's performance and project that onto another disease. mRNA allows the targeting of specific proteins. The efficacy of the T-cell and B-cell responses are going to be highly dependent on that protein's structure, its importance and level of conservation in the pathogen, and other factors.
COVID-19 seems to require a persistently high level of neutralizing anti-bodies and the T-cell response seems to be less important (and also plays a role in auto-immunity). On the plus side, the wild-type vaccine has continued to be fairly effective against even highly mutated Omicron which is surprisingly good even if strategically, it is suboptimal that the virus has continued to mutate and evade the vaccine to ever greater degrees.
The specific targeting makes it easier to allude the vaccine as only a small part of it has to mutate.
For example, natural immunity recognizes the entire coronavirus, not just the spike as the covid vaccine does. There was a study that natural immunity was more effective against the virus and variants because of this.
You could however have yearly subscription shots like we do now, just mRNA flavored that target the new strains, but there are hundreds.
I don't see the advantage mRNA would have over traditional vaccines for the flu, but for something like cancer or HIV it seems promising. Doing something your immune system can't do by itself.
Are COVID-19 vaccines the first successful mRNA-based vaccines? Seems to me there should be some other successful application of mRNA when it comes to vaccines/medications even before COVID-19. In that case, how much more complex was it to create a vaccine for COVID-19 specifically?
I understand why you think that, and it's true enough for most classical vaccines. But, the mRNA vaccines are different in at least five ways from the actual virus:
1. The spike protein it creates is structurally slightly different; they edited its structure to stop it collapsing in the absence of the rest of the virus.
2. The mRNA that codes for the spike is 'optimized' in ways nature either can't or won't do. In theory the optimized versions and viral versions are equivalent except for potency.
3. The mRNA is obfuscated to hide it from the immune system, which would otherwise immediately destroy it as being too dangerous to allow. This involves pseudouridine substitutions. It's a part of what makes the tech experimental.
4. The mRNA is protected by "lipid nanoparticles". This tech is totally different to what the virus does, and has caused unexpected toxicity problems in the past. In fact it's why mRNA based drugs never launched and why the COVID vaccines were the first outing for the tech despite it being under development for many years. They thought the toxicity wouldn't matter because the nanoparticles only become problematic on repeat dosings which, as everyone knows, vaccines don't require (doh).
5. The vaccine enters the body via a very different pathway, one which is far more likely to result in accidental injection straight into the bloodstream. For normal viral replication it often gets stuck in the nose, mouth, throat or lungs and can't reach e.g. the heart or the reproductive organs.
What are you talking about? No one suggested that the vaccine would prevent infection 100% reliably, and I'm not sure why you think we have a better understanding of the long-term effects of covid than mRNA vaccines (which aren't the only type of vaccine available in the first place).
>Regardless of whether you think vaccines should be required or not, the mRNA COVID vaccines have objectively proven to be both safe and effective.
By all existing measures of safety they're by far the least safe vaccines on the market, and even their apparent effectiveness may have just been the result of their immune suppressive effect: https://www.frontiersin.org/journals/immunology/articles/10.... .
>In support of this hypothesis, Dr. Netea’s group reported dampened transcriptional reactivity of the immune cells and decreased type I interferon responses in vaccinated individuals to secondary viral stimulation (97), while our group described inhibition of adaptive immune responses and alteration in innate immune fitness in mice with this platform (99). The immune-tolerant environment induced by these vaccines is further supported by recent studies that have discovered a correlation between an increased number of prior mRNA vaccine doses and a higher risk of catching COVID-19 (100–102). Thus, these data suggest that these vaccines’ efficacy in decreasing disease severity and death might lie with their previously undiscovered immune suppressive characteristics.
This is only partially true. The mRNA vaccines don’t generate the full protein:
> mRNA vaccines tell our cells to make a piece of the “spike protein” that is found on the surface of the SARS-CoV-2 virus. Since only part of the protein is made, it does not harm the vaccine recipient, but it is antigenic and thus stimulates the immune system to make antibodies.
Additionally, one of the studies referenced in the linked paper also states that negative thromboembolic events are observed in vector-based vaccines but are absent in mRNA vaccines:
> Here, we present first molecular evidence that vector-based vaccines encoding the Spike protein exhibit a problem that is completely absent in mRNA-based vaccines. This is due to the fact that during the vaccination step, the adenoviral DNA enters the nucleus and use the host machinery to transcribe its (trans)genes inside the nucleus.
mRNA covid vaccines are, sadly, in a class of their own. Compare with, e.g., polio vaccine:
> Two doses of inactivated polio vaccine (IPV) are 90% effective or more against polio; three doses are 99% to 100% effective.
> It is not known how long people who received IPV will be immune to poliovirus, but they are most likely protected for many years after a complete series of IPV.
Maybe! The fact that everyone "knows" that doesn't is the 1st concern. Even scientists are not clear on efficacy or long term beneficial/averse effects. Nobody knows why all previous mRNA vaccines were ineffective, yet, the Covid jabs are. Lots of questions still remain.
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