This body of research is expanding far quicker than I would have imagined pre-pandemic. A true silver lining, I have to say. mRNA vaccine breakthroughs are occurring in cancer research, too. Human trials happening soon! https://www.futuretimeline.net/blog/2021/09/13-mrna-future-c...
I have to say that we’re all being pretty highly optimistic since the first production grade mRNA vaccine looks like it doesn’t really give resistance for a long time to Covid.
>looks like it doesn’t really give resistance for a long time to Covid.
Easy to measure correlates of protection like antibodies wane over time, as expected from any vaccine. T-cells say a lot more about long term protection but are harder to measure. Generally, alarmist antibody research makes the headlines instead. I recommend the TWiV podcast by virologists and immunologists, which notably existed before covid.
Its worth noting that a 2x reinfection rate of a very,very,very small number is still a very,very,very small number. The difference between the high dose modern a approach and the low dose approach of other manufacturers seems to be pretty strongly significant, moderna appears to be working quite a lot better for longer.
It’s also important to note that for a first try, on an accelerated dosing schedule, 95% efficacy was incredible and blew all of the estimates out of the water. Falling to ‘merely’ 80% efficacy after several months and a major mutation still leaves you in a very good position.
Reinfection/breakthrough is exactly in line with what the parent poster is claiming, which is that it is due to antibodies waning naturally, either from vaccines or from natural infection. However, the B-cells remain and continue to recognize SARS-CoV-2 antigens, causing a rapid production of neutralizing antibodies within hours, as opposed to close to a week in the natural infection case. This leads to greatly reduced hospitalizations.
> There are numerous bodies of data supporting waning immunity at this point.
Why that happens is less clear though. Is it a fault of mRNA tech itself? Or the dosing schedule? 21 days is very close together for a 2 dose vaccine, most are 6 months or years apart.
Using 21 days was a good way to get the trials done fast, if they'd used 6 months we'd be where we were 5 months ago, but this was one of the risks. Canada, which spaced doses out further, isn't seeing nearly as high of a rate of breakthrough cases.
I'm not saying we can conclude definitely that dosing is the problem, but it's a question worth investigating before coming to any firm conclusions that mRNA vaccines aren't good enough.
Agree it seems likely that dosing plays a fundamental role.
Moderna while still seeming to suffer from this problem seems to be suffering less than Biontech, they are very similar in general, biggest difference is Moderna having already a longer minimum waiting period between the shots and a way bigger dose of mRNA per shot. So this may already be a hint.
Also currently it looks like a third shot is giving a really great boost compared to the second one, at least in the short term. Same with using mRNA as a booster shot after a vector based vaccine.
It’s weird that there is so little mention of natural immunity as a cause of declining measured “effectiveness”. The vaccine effectiveness should trend towards 0 as the unvaccinated population acquires natural immunity. That doesn’t mean the vaccine isn’t working.
Imagine a study where half gets vax and half doesn't. If population is pristine at outset at end of study VE is 1-ratio between people who get COVID in the two arms.
Now, if there is any prior exposure to the disease among participants (this isn't always known, esp. for something like COVID), and if there is any natural immunity that accrues, this will pull that ratio towards 1 (VE=0)
Probably the worst part about Covid-19 is that Sars-CoV-2 was a totally new Virus with a high attack rate, on top of the danger to the individual patient. If most of the population has seen "something like" it, even very distant variants will not be as bad.
J&J and AZ aren't really traditional either. They're Adenovirus based vaccines. Research has been out for a while, but I think there have been many production use Adenovirus based vaccines.
AZ is conceptually similar to the mRNA vaccines actually. They all target the Spike protein.
The Chinese vaccine is an inactivated virus kind of vaccine. That's what you would call traditional. Low protection from infection, but supposedly high protection from dangerous disease onset.
Not necessarily. As I understand it, several common viruses cause more serious disease further down the line. Even if you didn't develop warts, you wouldn't want HPV because some strains can develop into cervical cancer, for example.
Yeah, true the mRNA SARS-COV vaccines aren't all that effective after many months however, it could work better for things that don't mutate as much as Coronaviruses. It could still be magic. We just don't know yet it's all relatively new tech medically speaking and this is the current vaccines using the tech are the first ever widespread usage of the tech. We'll see how it goes long-term No one really knows how well or not it's going to go.
Yes it's way too early to draw conclusions. Think currently mRNA vaccines still stand strong compared to what else is on the market. Also one of the big promises of the mRNA technology is increased development speed so it might especially be helpful for things which mutate fast.
Can it pose a risk of making other mutations? and adding too much variation that ecosystems are not ready to defend against? All the arguments of the GMO, repeated (although it seems the GMO argument is settled).
The GMO argument is settled ? This surprise me. AFAIK, it is settled in Europe, but not in America where it is still authorized. Maybe I am wrong, I am not american.
Uhm the HSV vaccine pipeline seems to have changed. Excision had clinical trials scheduled for 2021 a few years back, if I'm not mistaken. There are about 4 billion people infected with HSV worldwide*. Excision could prioritize and deliver the HSV vaccine and have the company well-funded for other causes.
I recently found a great subreddit with a table in their stickied thread about the latest research on HSV cures and treatments. There are several cures under testing and we may see the first people cured of HSV in 2024:
Clinical trials are expensive so unless you're massively well funded (like Moderna and BioNTech are at the moment, and basically nobody else in that space) you have to prioritize for whichever is the most promising based on prelim data. This is a problem trivially solved with money, but for some reason all the promising biotech developers are massively underfunded compared to branches such as killing people or selling advertising.
hsv may have a broader market, but there is clearly a greater social benefit and urgency to new hiv treatments. hsv infection is essentially a minor annoyance compared to hiv which can be life-changing and lethal.
HSV is, iirc, one of the most significant causes of serious conditions like viral encephalitis. I wouldn’t be surprised if the net impact were similar to or greater than an HIV cure, considering that about 5,000x more people have HSV than HIV (order of magnitude estimate from a quick look at some stats I found online). Of course, the PR of an HIV cure is much better.
hsv encephalitis incidence is like 2 per million which is absolutely incomparable to hiv infection which has rates as much as 1 in 5 in some high risk populations and 4930 per million globally. the net impact of a new effective hiv treatment is indisputably more significant.
> hsv encephalitis incidence is like 2 per million
This can’t possibly be correct. It’s the most commonly diagnosed etiology for viral encephalitis, which definitely occurs more than a single digit per million. It’s also going to be underdiagnosed because the diagnostics are bad (fewer than half of encephalitis cases are assigned an etiology). I see several sources saying in the range of 2-4,000 confirmed HSV encephalitis cases per year in the US (which are usually extremely severe, leading to brain damage or death), compared to 5,500 “HIV-related” deaths per year in the US according to the CDC. So at the very least they seem similar in magnitude.
HIV is very manageable with drugs, and life expectations are very high. Whilst the disease is horrible, and we should be seeking a cure, its manageable. HSV is emerging as one of the biggest contributors to dementia. That is itself a disease that kills - just over a longer time span. Unfortunately for HSV there is little long term strategy for management that can address this issue. The *ciclovir drugs primarily target viral shedding, and not the rest of the infection cycle.
It takes non trivial logistical efforts to deliver HIV drugs to people. Think folks living in slums in south africa, homeless drug users in the USA, etc.
Is this the front leader in using CRISPR at the moment? The Radiolab podcast a few years back was saying that many labs started researching things so I imagine there's going to be a lot more biotech companies popping up soon.
Just like the renaissance that came after the dark ages.
Doesn’t that render every application of this tech net negative. I’ll cure you BUT give you many other incurable diseases. Imagine git had “git ai fix“. It fixes bug but also randomly changes code in entire code base and God knows how many runtime bugs now exist.
I wonder how much of this recent development can be attributed to the Covid pandemic—whether it's helped clear up a lot of red tape or whether the development has been largely unaffected negatively or positively.
And a lot has happened in the past 5 years already. From theory to human trials (curing sickle cell, liver diseases) to FDA approved treatment for blindness (Luxturna) and spinal muscular distrophy (Zolgensma). And its not just labs in America doing it.
This is in labs and startups all over the world. It's like a gold rush right now.
All this will do in mid and long term is they'll jack prices up even higher because they can, just went government did to college loans.
I was reading somewhere where people linked price growth to growth of medical insurance, the point was that add soon as people stopped print from their own pockets they stopped caring and started to take whatever doctors said and the companies started marketing to doctors and making agreements with then and so on and do on. Can't find the link unfortunately.
I won't try posting from my phone every again :picardfacepalm:. Because the edit button is gone now, I'll just re-write it in a readable way.
All this will do in mid and long term is that they'll jack prices up even higher because they can, just like what government did to college loans.
I was reading somewhere where people linked price growth to growth of medical insurance, the point was that as soon as people stopped paying from their own pockets they stopped caring and started to take whatever doctors said and the companies started marketing to doctors and making agreements with them and so on and so on. Can't find the link unfortunately.
I mean, I would pay $350 to have the peace of mind that I am immune. I don't engage in any risky behaviors, no drug use, monogamous relationship, but if my $350 protects me from a stay blood transfusion or freak accident and helps cover the cost of at-risk populations getting protected, then that would be fantastic.
That's not exactly true. Vaccines don't tend to be highly profitable, and R&D is often subsidized by the government. Salk's polio vaccine was developed in a university lab and never patented.
I oppose vaccine mandates yet believe, backed by good evidence, that the mRNA vaccines dominate any other COVID vaccine available. The two should not be related.
I can agree with you. I am not trying to press antivax or for vaccines. I am trying to highlight how terminology was changed to allow covid mRNA to qualify under the FDA.
I also was taken aback by the full on defense of 'capitalism' as it relates to the covid shots.
That was not a freemarket driven choice. It was paid for by the US government via tax payers. To conflate them because of social purpose, or whatever ideology people want is just wrong.
They stand to make decades of profit and it wasn't some high moral road. It was only for money.
Thats not how this works. Extra money goes to investors who then choose to do what they want with it.
Rather, seek subsidies and use the success to chase government grants and reinvest that money for the greater good.
It amuses me to imagine, how grandparent imagines investors cash out of biotech: buying a large pool of gold and swimming in it?
If you make a billion dollars on biotech... it has to go somewhere (banks are for chumps!), so it's going back into either the public market, or venture capital. And if you made a billion on biotech once....
Perhaps if PrEP were free so that it could be effectively used in developing countries, where, to my knowledge, at least some people still believe that having sex with a virgin cures HIV.
Yea but like, is everyone going to take PrEP all of the time? It’s great I’m sure if you’re planning on doing otherwise risky behavior, but in my experience, risky sex is never especially premeditated. It’s just a “just this once”, and then suddenly you’re buying plan B.
If you're the sort of person who does risky things you tend to know. Hooking up every night in the Castro isn't something that just happens, even if the acts aren't particularly premeditated.
Dunno, I think self deception is a powerful thing. I certainly have taken a number of sexual risks that, in retrospect, were really stupid, but I was able to rationalize at the time.
There are long-acting (e.g. 8 weeks) injectable versions that are outperforming[1] the daily pill so that approach shows some promise. Not that anybody enjoys injections…
Once every 8 weeks is entirely more palatable and manageable than a daily pill in my mind. Daily pill forgetfulness leads to things like unplanned kids. Unplanned kids are life altering, but generally not deadly, unlike a communicable disease like HIV.
I don't want to downplay the severity of contracting a life-altering disease like HIV, but with modern antiretroviral therapy the life expectancy for HIV positive people is actually about 70-80 years, though not that ART is side effect free...
Compliance can definitely be a challenge with pharma in pill form, but even with a modest amount of effort, it would radically reduce transmission throughout a population as those who are able to adhere to the dosage schedule would act as a firebreak in the greater population. Like those who are vaccinated against high transmission communicable diseases.
The UK is on track to eliminate HIV transmission within the decade [1] [2] assuming PrEP use within and near high risk populations. So, to answer your question ("is everyone going to take PrEP all of the time?"), that seems like a reasonable solution until a vaccine is approved for prevention and a CRISPR protocol is developed for therapy in the already infected. It may even take some time for HIV production to ramp, making prEP even more important so the at risk don't get complacent and an unnecessary bump in infections occurs.
(it's important to note that kidney function should be monitored in those on PrEP)
Oh, cool. I think I hadn’t thought my comment through very well - don’t need to get transmission down to zero, just r below 1. Prep plausibly helps with that
I am somewhat scared of this mRNA/fancy biotech stuff. We are really playing with fire and I dread to think what happens if we screw up. I don't think the way we test this stuff is sufficient. We need some kind of simulated unit testing for drugs.
I read on reddit in a long drawn out debate between to researchers was a concern that MRNa could triggering auto-immunity in case of covid treatment. As errors happen in copying/duplication. And covid treatments are training immune system to attack virus but error could easily train to target to some receptors on human cells.
Like another comment said, cancer, but that's probably one of the better ones on the list of possibilities.
Neurogeneration, mutation of gametes, accidental sterilisation. Let me be very clear - I'm NOT promoting an anti-science viewpoint here or saying that progress is a bad thing. I'm simply stating that we're in possession of powerful new tools and if we aren't careful, we're going to end up with more Thalidomide babies or worse.
Applying this new technology on people and then measuring the outcome is not an appropriate or ethical strategy. It's not appropriate because the consequences could be very hard to detect or not present themselves for decades. And it's not ethical because it's harder to predict what could go wrong.
This is an “anti-science” viewpoint though- you’re providing a bunch of hypotheses but no evidence for them.
And then you’re throwing in unrelated historical situations “Thalidomide babies” to evoke the “think of the children” argument, provoking moral outrage.
Finally you throw up a straw man to imply that science doesn’t generally use ethical practices, of which you provide no evidence for.
You mean 'I've personally seen no evidence for them'. Pharmaceutical companies are science companies big time. They do science and the stack of proven unethical practices connected with them is extensive as a spot of searching reveals. No implication necessary, We know they often don't
conduct themselves in a proper manner and often in a criminal manner.
To which we can add Eli Lilly, Amgen, Astrazenica, Actelion, Purdue Pharma all of whom have been fined upwards of $200 million. And these are only the big fish. Of course most scientific activity takes place such that ethical considerations don't arise. When they do however, it would seem that making a default judgment of their ethical probity is definitely problematic.
When you say "no evidence", what sort of evidence do you expect? The reason we generally run trials for many years is to gather evidence.
There was "no evidence" for the vaccines causing Myocarditis when they were rolled out. Now there's strong evidence and the concerns are growing. This trial reported Myocarditis rates at 1:1000 in a group with median age 33:
As for neurodegeneration, there is a concern that Codon-optimization[2] used for mRNA vaccines[3] can trigger it. It's simply not possible to gather evidence of that in the current approval timeframe, we just assume that the risk outweighs the benefit, come hell and high water. That may be a reasonable assumption for at-risk groups, but not for everyone.
The quality and the ethics of any scientific endeavor are orthogonal attributes. To me it seems that gp is simply stating that they are concerned that the power of these tools to solve problems could push society to adopt them at a rate that doesn’t allow for the longer term implications to be realized.
Thalidomide may be unrelated pharmaceutically, but the EUA for Moderna was issued almost exactly 9 months after the very first phase 1 trial started. How many pregnancies were brought from conception to full-term through that testing? CRISPR has the ability to modify genetic material in reproductive cells, causing heritable germline modifications. How do we test that?
Unfortunately the pandemic is distorting this conversation. There are too many subtexts around widespread rapid adoption, conflict around mandatory vaccination, avoidance of severe societal hazards, etc.
