Moderna will develop mRNA vaccines for some of the world’s worst diseases
singularityhub.com
singularityhub.com
I think this quote sufficiently answers your curiosity slightly. Not a lot, but slightly.
I’m not sure how mRNA vaccines get around that, but I imagine they have a plan, it would be interesting to hear it.
The issue with dengue in particular is a bit of a special case. Infection with a single serotype weakens the body against infection with other serotypes. Now. This poses a challenge to vaccination, as you need to find a way to get all four.
Currently, we have dengvaxia, which does do that. However, an interesting effect is that the vaccination is only useful if you already have a history of dengue. If you're dengue naive, the vaxx increases the risk of severe disease instead.
I was concerned about this potentially being a thing with Covid at one point. Thankfully not the case, but yeah...
Dengue has multiple strains. The initial infection with one strain tends to be not so bad and you may acquire immunity to it. However, it triggers a much worse, often hemorrhagic outcome if you acquire one of the other strains.
Vaccines, afaik mirror that property, changing the risk calculation by removing the less risky first infection.
First a WHO link.:
https://www.who.int/news-room/questions-and-answers/item/den...
>There is an increased risk of hospitalized and severe dengue in seronegative individuals starting about 30 months after the first dose.
TL;DR vaxx good if you've been infected before, but if you're dengue naive, it might raise the risk of severe side effects
Now, on the topic of an actual immunological phenomenon with a name out of /pol/'s fever dreams: An In-Depth Analysis of Original Antigenic Sin in Dengue Virus Infection
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014204/
TL;DR: Original antigenic sin describes a situation where the body's first exposure to an antigen shapes it's future response. This ends tragically in the case of dengue, where the response trained on a serotype is unfortunately overfit. Upon exposure to a different dengue serotype, the immune system defaults the response fit to the original infection, resulting in a response dominated by an inferior antibody. The outcomes are thus worse.
From what I'm seeing in more recent publications this model of dengue infection still seems to be the general consensus.
As to why I dug into this area in the first place, I live somewhere where dengue was quite the bugbear, and the "second time kills you" story was mentioned quite a bit. Turns out it's a pretty interesting area, since it clashes with the layman concept of immunity. I'm no expert in this domain though, so if I've missed out some progression on the science here, I'd really like to know.
Edit:
As others have also pointed out, there's also the case where the antibodies even enhance the infection process.
Since the immune response is for the older versions of the virus, getting the updated vaccine still ends up having the same effectiveness of the original vaccine.
[1]: https://arstechnica.com/science/2022/02/monkey-study-casts-d...
Effectiveness of the original vaccines against Omicron infection, in particular, is essentially zero after a few months:
https://www.medrxiv.org/content/10.1101/2021.12.20.21267966v...
It should be noted that the vaccines appear to remain highly effective against severe illness, even without boosting. The mRNA vaccines, in particular, seem to raise a robust, long-lasting cellular immune response, even though antibody levels rapidly fall. One of the downsides of the unusually rapid approval process for the Covid vaccine was that it was impossible to see this pattern in a randomized trial that lasted only a few months. This led "experts" -- people who really should have known better -- to oversell the shots as a form of sterilizing immunity. They are not.
There are good reasons vaccines take a long time to develop.
Updated vaccines are being looked into, but the original ones still work well enough that there is not the push to expedite the process we saw with the original one. With the virus slowing down to herd immunity, it is likely we won't see another such a push for this pandemic.
my understanding is that going from something in the lab to something that is produced at scale requires significant chemical engineering work, similar to, but likely harder than hardware which is based on parts availability and cost.
all warp speed did was release money and allow process development and testing phases to overlap, is my understanding.
There's a prioritisation issue. There are so many diseases, and many more proposed treatments. Without a good reason to jump the queue there are bound to be delays.
There's also the efficacy testing issue. Your phase 2/phase 3 test subjects are mostly young european males (Uni-students). Without deliberately exposing them, how likely are they (and the control group) get infected? It could take years for a statistically significant number of the control group to catch the disease.
When there's a pandemic on you might hit those numbers in a few weeks.
In the future they might prepare a wide number of vaccines targeting common coronavirus ahead of time so there can be quick response when an outbreak appears.
Think of COVID as a human being. The mRNA vaccine teaches your immune system to recognize and destroy hands instead of a whole person. As a result your immune system can detect all shapes and sizes of people as long as they have hands. It is possible for the virus to mutate to use claws instead of hands, but then it isn't as effective at grabbing cells to infect them.
In the case of an incredibly rapidly mutating virus like COVID-19 it's just not worth it to go through that whole process every time it goes from hands to claws to hooves.
It's not that it's not worth it, it's that this approach doesn't work. Evolution is a remarkable force, and unless there's a good reason for the part of the virus/bacteria/amoeba you're targeting to stay that way, it will change to escape the selective pressure against it. We're more-or-less seeing this with SARS-CoV2, even though the virus is a relative amateur at genetic drift.
OK, you may say "let's target the vaccine against a part that doesn't change"...that's great, except that those parts tend to be so common -- so "evolutionarily conserved" -- that you see them all over the place, including, often enough...your own body. Train your immune system to (over)react against common antigens, and you're going to cause problems.
The primary reason that vaccine development is difficult is because you have an extremely high bar for effectiveness, coupled with an extremely low bar for side-effects. And even if you find such a unicorn target, you have to make sure it stays magical over time. The mRNA technologies are great and do accelerate things, but ultimately, the speed of the Covid vaccine development process was more about our willingness to throw huge money at the problem and eliminate all development and liability risk, than it was about any particular technology platform.
Nope, the Moderna vaccine was designed in 2 days after getting a full DNA sequencing of the virus. Very rapid design is a particular feature of mRNA vaccines (with the caveat that sequencing to find the right proteins is required).
Said differently: the slow part of creating a vaccine is doing the trials to make sure you have safe and effective target.
The conclusion said it is less effective.
The messenger RNA (mRNA) boosters were highly effective against symptomatic delta infection, but they were less effective against symptomatic omicron infection. However, with both variants, mRNA boosters led to strong protection against Covid-19–related hospitalization and death. (Funded by Weill Cornell Medicine–Qatar and others.)
Don't get me wrong, I believe in the vaccine, but I think we are still far away from one vaccine that kill all the the mutations.
In this study, mRNA boosters were highly effective against infection with the delta variant but were less effective against infection with the omicron variant. However, these boosters led to strong protection against Covid-19–related hospitalization and death due to both variants.
We vaccinate in order to prevent severe disease, hospitalization, and death. The original vaccines, per the link you shared, are extremely effective at this.
There seems to be a pervasive thought that our leaders ought to somehow become superhuman and obtain clairvoyance about how to solve any problem we have. They are no different from any of us, who think a bug has a simple solution before we spend a lot of time figuring out more complicated things were happening under the hood.
The new information, that the world is globalized, with many countries not being able to afford vaccines and also many militant anti vaxxers around?
How was wiping out covid, a realistic goal in the first place?
Similarly, a lot of people have been claiming we're evilly withholding patents from the world, but that can't be a real issue or China and Russia would just have stolen the IP from us. They literally can't produce them any faster even with the rights.
The CDC needs to be explicit and clearly admit that it was wrong or the data changed, and that vaccinated/boosted people can and will get sick or even spread disease to others. The new 'deal' is that they will likely not be hospitalized or suffer severe disease if infected.
Far too many people are still walking around thinking their shots and booster, now nearly 6 months old for some, are an impenetrable force field against any sickness.
I remember last year when this news hit, that bit about 90% effective *against infection* was amplified and played nonstop for the public. The message was clearly get vaccinated and you will not get sick.
It was not until July and the CDC MMWR report on the Providence, Rhode Island, bear week festivities that lead to unexpected breakthrough infections that the CDC admitted the vaccines were not 90% effective against infection anymore. Unfortunately this updated message has never been clearly told to the public, at least not as clearly or loudly as the original 90% protection against infection message.
Btw, I’ve had both shots, had COVID and will get the booster.
That is unfortunate that we switched to directly getting mask policies etc. from them, because it's not their job to consider tradeoffs and they aren't good at it.
> Walensky was referring to a new CDC study of nearly 4,000 front-line workers, some vaccinated and some not, who tested themselves weekly for COVID-19 infections between December and March.
> But more data is still necessary to say so definitively, which is why researchers are recruiting thousands of college students across the country to find out more about the likelihood of asymptomatic spread of this virus among vaccinated people.
The article is explicit that the CDC was talking about the findings in a new study, and that more research still needed to be conducted before being sure of their findings.
> It was not until July and the CDC MMWR report on the Providence, Rhode Island, bear week festivities that lead to unexpected breakthrough infections that the CDC admitted the vaccines were not 90% effective against infection anymore.
Because of the new delta variant that those very same festivity goers helped the CDC with[1], and that changed the CDC's guidelines:
> The speed of the investigation — and the exceptional participation from the mostly gay men involved in the outbreak — helped the CDC learn new information about the delta variant. And it was that new information, in part, that prompted the agency to change its guidance for how vaccinated people should keep themselves safe at this stage of the pandemic — including a return to masking indoors.
[1] https://www.npr.org/sections/health-shots/2021/08/06/1025553...
That's a direct quote from the head of the CDC, it does not get more official or more of a primary source than that IMHO.
1. It's still pretty effective against COVID
2. Clinical trials showed variant specific versions weren't that much more effective
3. Protecting against the granddaddy strain has a much broader effect than protecting against a new strain.
Well, besides imagining, we're also doing science, so what does the data that you've seen say?
Perhaps there is a reason the original vaccine would be expected to be more broadly effective, as my parent said. It's not intuitive to me, but that doesn't mean it's wrong. Hence my question.
Specifically I was objecting to "Given X, we wouldn't expect Y to happen" aspect of your argument. Its never so simple with the human body! It works in many other domains, and so as a former programmer myself I have to catch myself trying to apply such reasoning to biological systems which can't be modeled like that.
https://www.technologynetworks.com/vaccines/articles/the-hun...
Perhaps there's a fear that an Omicron targeted vaccine would allow a more deadly variant to take over again
[1] https://www.cnbc.com/2022/02/28/pfizer-covid-vaccine-was-jus...
Delete your comment to save face?
The problem as I understand it is that it isn't profitable for either company to take a risk on producing these boosters at scale. They have to take a bet that the variant they target for the booster will be the one to dominate in the next months, and right now with variants like omicron mutating and growing at astounding rates it is quite risky. If they target the wrong variant that's a whole lot of completely wasted vaccine doses and they have to start over again. As I understand it their production lines are limited too and can only produce one specific type of vaccine or booster at once (i.e. wild type or new variant, but not both).
Honestly we need operation warp speed again. It needs to just never stop, at least while we are in such a critical stage and massive amount of virus spread. We need the government and the billionaires/trillionaires to bankroll parallel development of all major variant boosters at once.
This makes sense defense-wise, as well, because the arms race in vaccine development is also an arms race in producing vaccines for diseases you intend to use as weapons. A disease a group has a vaccine or cure for, but no one else does, could be weaponized.
For the initial wave of COVID-19, it was an absolute necessity, but unless our backs are pinned metaphorically to the wall, is it really worth taking a short cut? In the best case, COVID-19 will become endemic (prevalent every season, but not as harmful for the majority of the population)... so wiping it out by way of universal uptake of a given vaccine is not (and never was) on the tables.
A weaponized virus would inflict untold suffering, but there is nothing to stop another Operation Warpspeed. Having OW active all the time? I don't see that being a good thing.
IIUC: This means that they would essentially be supplying the new pressure and stressors required for the virus to be forced into mutating more and more since its current environment is not suitable for its current arrangement. Every time it replicates there is a chance for mutation, but greater stressors increase that chance of mutation. Depending on the stressors, the mutation may or may not occur in tandem to that stressor. I.E. Vaccines increase immunity? Virus gains ability to breakthrough easier.
Now that may be a rather simplistic understanding of it, I admit; but this does seem to coincide with what is essentially happening so far this past couple years.
1. New variant emerges. 2. More people get vaccinated. 3. Old 'new' variant dies off 4. New 'new' variant picks up. 5. More people get vaccinated, or re-vaxxed. 6. Old 'new' variant dies off, again. 7. New variant emerges, or a subvariant, or double mutation. Repeat.
Eventually we will all be vaccinated 3 times or more, easily. Or at least a very large majority of us. What happens when some super variant emerges and has the capability to breakthrough all that resistance?
More vaccines?
You do see where this is going, right? Doctors and scientists were concerned about a very similar situation with anti-bacterial resistant bugs. Stuff like H.Pylori in hospitals if I remember correctly. Well, now we have the same situation potentially occurring on our hands.
We can only hope that the mRNA vaccines or something better is/are able to keep ahead of the game. The only way we are beating this thing out, is by completely snuffing it out. And that's going to require removing all its potential hosts.
That means we might have to vaccinate wild animals, because deer have been catching it for instance. And apparently spreading it in some cases. Once so far for sure is confirmed I believe. So yeah, Deer-vid is a thing now. Hooray?
It's going to be either a lot of animal vaccinations going on out there... or a huge culling. Of all sorts of animals. Or letting them catch it and suffer through it for better resistance for a time being; and then hoping to snuff out the virus finally at that point.
I'm sure you can see how hopeless this all is at this point. It's part of why the politicians are now saying "we need to learn to live with Covid."
And I agree, I guess. Not really much choice at this point. It's here to stay in its current forms, and further. For now at least.
So, huge advantage? Sure, maybe. Depends on your goals.
And the hospitalisation rates for Omikron are still way too high compared to how fast it spreads, at least for most healthcare systems.
I hope I get better without having to visit a hospital.
What should I get tested for after getting better?
Did you go for this as routine checkup or after some symptoms, or you wanted to see what damage was caused by COVID?
I'm gonna do an electrocardiogram next week, and based on that the GP might do some other tests. So you should listen to your body and try to have little stress, no drinking, no hard sports for a few weeks, and contact your GP if you don't feel good.
Now fever is down. My 5th day of symptoms today. I’m going to repeat CRP and then additionally do a chest CT scan today. She will see whether all is well or almost well with me or do I need specific care as of now or later as part of recovery. I think I technically I am still a covid patient.
And god, why is it difficult for every doctor out there to understand and accept that my “normal body temperature is below 98.6 F”!!
However, it does seem like it's not necessary to make people get 2-3 vaccines if they caught it.
> The large majority of the cost (about $850) was the peptides
If we could produce just the peptides at scale then everyone is free to produce local vaccines. Not sure if the peptides themselves have the same extreme storage requirements as the vaccines do. If we can give every country the techniques to build their own vaccines we wouldn't depend on mega-corps and some of the "anti-vax" arguments would become moot.
The answer is a "pancoronavirus" vaccine that'd work against all of them, but it seems that using mRNA or not doesn't actually help with that.
The article (and its linked source) mentions Chikungunya, Crimean-Congo hemorrhagic fever, Dengue, Ebola, Malaria, Marburg, Lassa fever, MERS, and COVID-19. Reading through the articles in depth also reveals mentions of Nipah, HIV, and Tuberculosis. That's 12. So what are the other 3?
The thing with dengue is the first time sucks but catching a second variant is often fatal.
edit: The best i can tell its Bayers take on the topic, gene/cell therapy being bad PR. https://youtu.be/OJFKBritLlc?t=5850
It probably helps that there's now a well develiped framework for mRNA and adenovirus vector vaccine approval, but ultimately any new antigen could certainly be unsafe and future candidates are going to require every bit as much testing and won't get most of the expeditiory benefits the first generation of COVID vaccines experienced.
There are still other steps that take time. You need to figure out what is the mRNA you want, then you need to test a new vaccine candidates for adverse effects.
The best explanation I've heard for it; is that given by Stephane Bancel (Moderna's CEO) to the (excellent) Bio Eats World podcast in the episode "The Machine That Made the Vaccine" (https://bio-eats-world.simplecast.com/episodes/moderna-covid...)
His explanation goes something like this [0] ...
1) If developers have target protein(s) they know they need to get the body's cells to synthesise to fight disease. Then the key advantage of mRNA technology is that it makes activating this a _turnkey_ operation.
2) With Covid-19, humanity got lucky, the target protein(s) were identified very early in the pandemic, and they have remained useful [1].
These, combined, allowed them to construct a viable vaccine quickly (days) before they had any physical access to the virus. [3]
These new announcements are for diseases where targets are similarly well-identified (and promising from a therapeutic pov). I think the potential for this technology to improve the human condition is, to put it mildly, incredible.
[0] I'm an SW engineer, and it's been over a year since I listened to the podcast, so apologies to anyone if I mangle this.
[1] For some diseases, this is apparently not the case, e.g. AIDS
[3] Of course it then needed the same standard, thorough acceptance process, albeit accelerated by running parts in parallel, before being released to the general public.
I live in a country where dengue is a horrible threat, so that would be amazing.
The article goes into this with more clarity, depth and accuracy than my capsule summary above.
See also https://pubmed.ncbi.nlm.nih.gov/33194810/ .
Basically people develop antibodies that make future infections worse by potential infections the infectious proteins.
The challenge is not creating a vaccine that stimulates an immune response, the challenge is avoiding a response that makes things worse.
> The challenge is not creating a vaccine that stimulates an immune response, the challenge is avoiding a response that makes things worse.
Agreed. This is probably always true, there’s just more concrete evidence of this potential outcome with dengue.
Antibody response is not necessarily the same, even in the same person with the same antigen.
The immune system basically creates a ton of random antibodies and when they “hit” on the previously unseen antigen, they are amplified.
Now once someone has had an immune response and generated memory cells, then yes, very similar antigens (that somewhat bind to the exist ones the body made prior) will tend to “narrow down” the antibodies generated to varieties of the original one (the immune system basically says ‘these old antibodies are close, so let’s create variation off them to optimize the new ones’).
Then the other thing to consider is that there are different strains of dengue - so you could get type A, generate a response, but then exposed to type B where your type A antibodies activate the infection mechanism rather than disable it.
I’m thankful I had access to good healthcare, otherwise I wouldn’t have had good luck with it.
I also had Chikungunya virus once when I was little. Not fun. We need to eradicate these diseases for good.
The main problem with producing vaccines is not principally the delivery platform, but the difficulty in generating a sensitive, specific, and effective immune response to your target bug. This problem has plagued immunology for decades (and is a bit of a black art), and sadly may not be solved simply by using mRNA.
Nevertheless, promising news. Presumably this is funded at least in part by the significant profits Modena has generated from the COVID vaccine.
but was it successful? the covid vaccine loses effectiveness after 8-12 weeks. i don’t know if this is specific to sars-cov-2 and it’s mutations or the mrna delivery platform.
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.
I would love to get a safe and effective HIV vaccine, but I wouldn‘t take it if it could give me a heart attack!
It won't surprise me to hear down the line that something subtle went wrong in a sizeable proportion of injectees, and that maybe we rushed into this without taking the time to gather longer term data. Think long term immune disorders, which are difficult to diagnose, especially early on.
It wouldn't exactly be the first time we've screwed up.
Umm,no.
I guess live vaccines are kind of like that, but its still a misleading description, and most "traditional" vaccines aren't live vaccines.
A “diluted viral load” is a very unsafe vaccine. “diluted” means “less of” and basically means infect ourself “with less of the virus” and hope for the best. The virus by definition is an unsafe mRNA payload (sometimes the virus will first burrows into our DNA which then creates the mRNA) that will hijack our cells and reproduce itself until there is a large enough viral load that can trigger immune response.
For an effective and safe “old-school” vaccine we would need a “dead or disabled large viral load”. “dead or disabled” typically means “can’t reproduce” and/or “can’t produce the problem viral proteins” and basically means the amount of virus in our bodies at all times is roughly the amount in the injection. This has to be a large enough “viral load” to trigger immune response.
The new mRNA vaccines are attempting to be safe mRNA payloads pretending to be the unsafe virus by using very small parts of the unsafe virus (e.g. only the spike protein) but this safe mRNA payload will “reproduce” inside our cells creating a lot of spike protein. They create a large enough “viral load” to trigger immune response.
There is no body without mRNA and there are basically no viruses that don’t leverage mRNA and therefore all previous vaccines used mRNA we just didn’t have good technology to use it directly.
I hope this helps clarify that “diluted viral load” is an incorrect oversimplification for old/new vaccine science. To understand “old school” vaccines, you would be better off with “boiled viral load” or “cooked viral load” as the oversimplification.
First off, no, these vaccines are not like standard vaccines, standard vaccines do not introduce the formation of a pathogenic protein in both quantity and quality to that of the pathogen itself which it is attempting to provide protection against. Standard vaccines also do not hijack cellular functionality to produce these pathogenic proteins in both quantity and quality equivalent to that of the pathogen itself. Secondly, you cannot say the vaccines are this or that compared to anything else as these experimental vaccines are not uniform in either their viability or their consistency as a breakdown of batches from the VAERS data reveals 5% of vaccine batches are responsible for 90% of all adverse reactions across all vaccine manufacturers. And if by efficiency you mean having the cells of sensitive organs expressing an overabundance of pathogenic proteins on their surfaces which induces the immune system to engender cellular damage and oxidative stress leading to apoptosis— all incidences which have been documented by the pathologist Dr. Arne Burkhardt—then you need to reconsider your definition of efficiency. We, even to this day, are still not fully sure of how a spike protein interacts with the human organism and the evidence which has come out over the past year shows that the spike protein can affect human cells in multiple different ways which were not taken into consideration by the vaccine manufacturers. The only difference between the complete viral protein and the vaccinal proteins are the inclusion of prolines which supposedly lock the vaccinal spike protein in a state of prefusion but with 1.2 million adverse reactions recorded in VAERS and 25,000 vaccine-associated deaths it's safe to say the prolines don't work as expected and that the vaccinal spike proteins are just as pathogenic as spike proteins which are expressed by SARS-CoV-2.
But your flaccid argument not only fails medically it also fails legally. Even legally these vaccines fall under a completely different set of laws that prevent compensation to those who have been injured. These experimental vaccines are not being treated in the same fashion as standard vaccines as there is a judicial process available for standard vaccine injury where patients are compensated for a vaccine-induced injury as determined through a court procedure which has an appeal process. Compensation for injury or death from these vaccines are instead subject to the heavily restrictive Countermeasures Injury Compensation Program (CICP) instead of the much more robust National Vaccine Injury Compensation Program (VICP):
https://www.hrsa.gov/cicp/cicp-vicp
There is no judicial process for people injured by Covid-19 vaccines through the CICP as is stated on the HRSA website.
Your entire comment is ignorant and I have only begun to dissect it. But it shows you how two seemingly innocuous sentences can hide an entire underbelly of wrongdoing. Remember, when you point the finger you have several other fingers pointing right back at you.
If you are reading this and are at all interested in what I've written here you can read my full argument against these vaccines and their mandates here where I go into these ideas and many more:
What is your typically tend to source?
The human body is in delicate balance and there's a lot that can go wrong. Medical science unironically has only come so far - we just recently discovered the glymphatic system, and that's orders of magnitude in larger, in scale and energies, than cellular level chemical dynamics. Within and without our cells is a soup of thousands of subtlety interacting compounds which is poorly understood.
The immune response drops off relatively quickly hence the need for boosters. If the vaccine was cooking the immune system we would've started to see evidence of that long ago.