Current RNA vaccines protect against worrying coronavirus variants
nature.com
nature.com
The actual article said "modest antibody evading capabilities“
I hate that the internet has become this way
I have an appointment to get my first jab in 43 hours from now and I am bouncing back and forth between getting it and cancelation.
Five years ago I would not be having these doubts but it seems like everyone has alterior motives.
I wish the social media giants would just stop all the censorship and allow the discussions to take place. I appreciate that they are trying to stop disinformation but I just can't think of one time in the past that the ones stifling free speach have ever been on the right side of history.
The key thing you should notice about the COVID vaccine detractors is their inability to distinguish between vaccines and the wildly different technology between the different vaccines, alongside their inability acknowledge the geopolitical hurdles for any of their conspiracies. If a German-company made vaccine is part of an insidious plot, then should you get the Oxford one developed in the UK? If Bill Gates is influencing vaccines in some strange scheme, does the conclusion mean you should trust the Russian Sputnik vaccine more instead due to the geopolitical impossibility of a Bill Gates plot being involved? The absurdity basically cancels itself out, just get the shot you are offered.
Each of those vaccines come from a UN/WHO member country.
Geo politically power is wielded by globalist financial elites. These elites generally believe the world is overpopulated. Bill himself is well known for his this belief. Bill as an example runs a charitable foundation that only ever seems to make money.
These conspiracies are not constituted of a flat earth and aliens. They are of human hierarchies, corruption, and psychopaths.
If your idea is based on the existence of psychopathic financiers controlling organizations that every country on the planet is part of, and every vaccine production as well in those countries which use completely different technology, then you have left no oxygen in your mind for disproving anything. You've now exempted China from any scrutiny, in exchange for psychopathic financiers that would have much difficulty in collaborating with the party and maintaining status with them. You've replaced that with an insidious plot that makes zero sense and at the best requires opportunists to simply seize onto the reality. But that makes zero sense because the mRNA vaccines were sequenced within a week of getting samples in January 2020 because the technology is simply impressive and is the lifetime work of the Hungarian researcher. Ah, so many problems with this idea.
Now you want to talk conspiracies to conceal or coverup how the virus came to be, I'm all for that but I don't think billionaires want to kill off all their neighbors just so they can have the earth all to themselves. They enjoy the power and control over people and policy too much for that.
It's because social-security/pension systems are a pyramid schemes that can't sustain themselves without ever growing population. I consider many Western EU countries overpopulated (UK, Italy, etc), Google Maps satellite images also do a pretty good job at portraying at just how overpopulated the earth is. Pop growth every decade is still insane.
So you'd be fine with a Taiwanese vaccine then? That's the only country I know of that has significant medical R&D and is one of the few countries not in the UN or WHO.
My main concern at the moment is: Just as the virus can mutate during it's replicatative phase and produce variants why can't the spiked protien during it's production or the cells producing it mutate also?
If these production cells can mutate or the spiked protiens themselves mutate is it reasonable to assume an autoimmune diseases may result as the cells or protiens accumulate in my organs, limphnodes, fat cells or other areas?
This is an honest concern that I am hoping can be resolved, rather than be dismissed or attacked.
As every medical expert has been saying for months now, the vaccine doesn't effect your DNA.
The immune response is what causes the side effects, and the immune response is stronger with the second dose (this follows intuitively from immunity being more robust after 2 doses).
The first one, some of your cells get told by the mRNA/adenovirus vector (depending on if you had Moderna/Pfizer or J&J/Oxford) to make some 'rona spikes. Your immune system amped up a little bit and your cells feel bad for a bit because of having to spew out spike. Your immune system, which is a little amped up, sees all this and starts to formulate things to kill the spikes (antibodies) and starts to send out other immune cells that clamp down on the cells that are making the spikes.
The second shot? Your cells get the call from the mRNA/adenovirus vector and start spewing out spikes. Your immune system recently saw this so it _really_ starts spewing out more antibodies to get rid of the spikes and more of the other cells to get rid of the spike producers. It it is really ready for the fight and wants to make sure you're ready for the fight in the future too.
The negative side effects are your immune system causing parts of your body to do things it doesn't usually do (like raising your body temperature to help kill off cells that are making these "rogue" spikes).
The mRNA molecules in the vaccine just contain the instructions for the spike protein. https://berthub.eu/articles/posts/reverse-engineering-source... has a good breakdown of what specificly it makes.
To use an analogy to a computer - DNA is like the hard drive (long term storage but slow), RNA is like RAM (short term, degrades easily, but easy to transport and gets info where it needs to go), ribosomes are like the CPU (executes the code in the RNA, outputs a protein). Normally, DNA gets copied into RNA, which instructs the ribosome what protein to make. The vaccine is like inserting a fake message. The ribosomes see RNA and follow the instructions, but the RNA came from the vaccine instead of the cell's DNA. This is one of the reasons why the vaccine is so safe, because RNA just naturally breaks down very quickly in the body.
Booster generally causes more side effects, because the body has seen the spike protein before (from the first vaccine) so it recognizes it faster and mobilizes a more robust response. In a certain sense, its already done a practise run, so the body kicks things into high gear right away.
[IANAD]
After I read it, I noticed that it was the first time anyone had ever tried to explain _exactly_ how these new vaccines worked, like down to the molecular level.
Most explanations I had seen were usually extremely high level (literally just "the RNA gets read by your cells, which then produce the spike protein, then the RNA is destroyed") or used analogies (as you have done here).
I don't consider myself a conspiracy theorist, but I admit I had been harbouring some concerns/fears over these new vaccines. This link is the only thing I have read that actually allayed those fears.
I think there is a lesson here.
I have a feeling that everyone fears stuff they don't understand, at least a little bit.
I know that the high level explanation is technically correct, but here's the problem: Many conspiracy theories are actually _extremely_ detailed. I have personally seen covid conspiracies that appear to be backed up by scientific papers.
This is what the truth is competing against. A basic, high level "ELI5" explanation is never going to convince a conspiracy theorist who is looking at a stack of science papers.
So I think this link is very important, more people need to read and share it.
BTW: different people have different immune systems, and their body reacts differently. I got my first dose in the morning. By afternoon I just felt tired and wanted sleep (I felt like I didn't sleep the previous night). I went to sleep and next day felt normal. For 2nd dose the same thing happened, except I felt like that one extra day. My vaccine was Pfizer.
Everyone says the second dose is worse although.
Not to detract from people who did have side-effects, merely pointing out that it's possible to have none.
The nurse was a talker, and distracted me from watching what she was doing. I didn't see the shot go in, and I felt absolutely nothing. I only realized it was done when she said I did not bleed at all and didn't need a bandage.
Every other shot I've ever received I felt, but every other one I was also watching when it happened. Now I'm wondering if feeling them was imaginary, something my brain made up because I saw the jab and expected to feel it.
The mRNA in the vaccines have been engineered to resist degradation in the body, and stick around for as much as 2 weeks. Also, they degrade to nucleotides.
That's incorrect, in the sense mRNA does not alter your genetic material.
> why can't the spiked protien during it's production or the cells producing it mutate also?
They could, but they only exist for a short while and don't create new things. When the virus mutates, it can pass the mutation on to the new "child" viruses. Mutations that make things worse (for us) are super rare, so it only matters if there is also some method to preserve the mutation, select the ones useful to the virus, and make more of them. With the vaccine, it only acts for a short time and cannot "spread", so any mutation is immediately lost.
> If these production cells can mutate or the spiked protiens themselves mutate is it reasonable to assume an autoimmune diseases may result as the cells or protiens accumulate in my organs, limphnodes, fat cells or other areas?
Probably not. There is no method for the mutation to become dominant and take over, so you would have a single mutated cell which isnt enough to affect anything. Ignoring that, the vaccine acts for a short time, so stuff wouldn't generally accumulate because of the short time frame where the vaccine is causing spiked proteins to be created. After the vaccine is used up in your body, no more spiked proteins are created.
Note: I am not a doctor, my understanding may be flawed.
A list of the variants and their DNA code? Or whatever makes them vary.
A solid explanation of how these variants are more infectious, not just saying that "The numbers show it" but instead what is the real world physical change in the shape or attack vector that makes them more dangerous, or admiting it is unknown but being studied.
True numbers of deaths caused by covid and vaccines, you can't have it both ways and say "They tested positive for the virus and died so it was covid" then at the same time say "yes they got the vaccine but people die all the time, it wasn't nessisarly the vaccine."
A genuine record of which vaccines the well to do have recieved. Eg: Celebrities, Politicians, Billionaires. I suspect there are a lot more Pfizer going in their arms but they are telling the rest of us to take what we can get.
Maybe drop the racist, sexist, political anti white, anti male, anti Trump bullshit for a while in the media, because fighting the pandemic is just so much more critical right now. Instead of being opportunistic assholes and pushing those adgendas while everyone is scared, locked down and having their loved ones die alone?
IDK there is more, like the stuff comming out about Faucci signing off on funding banned research in Wuhan or the 2015 chinese report on weaponizing coronavirii but I think the first couple items on my list would go a long way. And before I catch a bunch more hate Ill leave it there.
Why a mutation improves transmission takes a lot of investigating to understand. I am not sure why you were under the impression that we know the mechanisms. If you type something like “E484K molecular dynamics” you can find a lot of computer simulations trying to investigate the mechanism, this is standard biological research. Of course we E484K you have a mutation from a negative to a positive residue, so that might give you a hint why it’s harder for the antibody to stick.
I can assure you that here in Japan we do not care about Trump. Perhaps we should be more grateful to his good support for the Pfizer vaccine, which is the one we are now deploying at scale (after the government here did their own review of the evidence).
You're the one who is asking SOCIAL MEDIA companies (i.e. Facebook and twitter) to educate you more. "I wish the social media giants would just stop all the censorship and allow the discussions to take place."
Maybe that's the issue all along. Shouldn't have random people and nefarious state actors provide your education, but maybe go out there and read reputable sources, read peer reviewed trial data (The Lancet), read about the success of vaccinations in countries such as Israel.
Not Facebook and Twitter.
okay you're just a troll. Got it. Fun...
I am still not 100% convinced but a decision needed to be made and based on the information, a large amount recieved here I chose to get the jab.
So now you have a slightly different protein produced by one particular cell for about 20 minutes. Big deal.
The tumor cells in your body right now are already doing a lot worse.
Bill Gates on the other hand says these vaccines are too complex and that safety and security issues[2] make it impossible for anyone else to produce these vaccines.
The media keep saying "even mRNA vaccines that are new don't enter the nucleus or alter DNA." Guess which could do that? The viral vector vaccines that have custom DNA run in the nucleus, which then produces the mRNA. This MedCram video[3] explains it better than me. Everything around the messaging for vaccines in mainstream media is so misleading if you look at the science. I don't know how someone couldn't be at least a little suspicious.
I have longcovid btw, I'm not getting the shot. People repeat BS to me like the vaccines will cure longcovid. They offer no proof whatsoever, no plausible method of action, and go off the media narrative how it "could help some people." I'm on longcovid forums, I trust the anecdotal experiences there than anything in the media.
[1] https://en.tempo.co/read/1445856/16-million-sinovac-vaccines... [2] https://www.indiatoday.in/technology/news/story/bill-gates-b... [3] https://www.youtube.com/watch?v=13qT7wLxkvU#t=1m30s
Both I and my wife had the J&J vaccine a couple months ago. We had a period of about 12, maybe 18 hours of feeling like we had a light case of the flu, and fine since. The J&J and AZ vaccines also use your cells produce spike proteins but do it with a different way (adenovirus vector) than the mRNA vaccines.
Sorry, what is the downside to getting the vaccine in your mind?
We are at the the point where society needs people to receive a vaccine, or it will stop functioning. How much are you willing to personally sacrifice so that someone near you has the option to avoid getting a couple of shots that a billion other people have already received?
Factories can't run at full capacity until people are vaccinated. Our food supplies, specifically meat, are at risk until people are vaccinated. We are going to keep this society of scarcity until ~90% of people are willing to get two shots.
You'll get a sniffle/fever for a few days and then be immune.
Don't put an experimental drug into your body for no reason.
Anyone who says variant or strains are a problem has merely to look at over 50% of the United States with no covid restrictions for months who are at record lows of infections and with minimal vaccines.
The variant or strain problem is a nothing burger.
Viruses that we've developed vaccines for, that have eventually been rendered inneffective due to a mutation? Is it a common occurence?
Another way of looking at this is that they're not new mutations that we scramble to develop and test vaccines for, we just roll out the same tried and tested vaccines, but we have to cobble together a different blend some years.
If the above is correct, then I guess the Flu example to answer my question would be: How often is a new variant of Flu (HxNy) discovered that necessitates a new vaccine being developed?
Generally the vaccines are moderately effective, but it's because we update them every year. If we didn't, they wouldn't be.
That being said there are efforts underway to make vaccines that would be more broadly effective against the flu and will be less susceptible to variants escaping ("universal flu vaccines"), and so this may not always be true in the future.
In the meantime, mRNA vaccines will likely be a huge aid for fighting the flu, because they can be manufactured rapidly for specific strains. Currently there's a six-month or longer lead time for inactivated- or attenuated-virus vaccines — which is what flu shots generally are — and sometimes new variants pop up or are discovered to be more infectious in between the manufacturing start date and that year's flu season.
Moderna apparently plans to make COVID booster shots that are also flu shots, although they may not be ready this year.
OK, this is the part I wasn't aware of. I assumed (dangerous, I know) that each year's 'new' flu vaccine was really just a new 'blend' of existing proven vaccines, for the most prevalent strains that year.
Edited to remove badly conceived question. New Question: How often do we have to develop novel vaccines for new Flu variants?
As I understand it predicting which flu strains to vaccinate this year is particularly hard because mask wearing/isolation/social distancing has reduced flu levels enough that they don't have a lot of data to base their predictions on
That being said, the process generally doesn't change — you still grow and kill (or grow and weaken) viruses the same way, you just start from a different base strain. For already-approved inactivated-virus flu vaccines, the FDA does not require new clinical trials for strain updates, and for already-approved attenuated virus vaccines, they only require very minimal trials (300 adults to prove adequate attenuation) [2]. So they're not novel in the sense of the COVID vaccines, which needed large scale clinical trials to prove efficacy — the flu vaccines have generally already proved efficacy, so for strain updates the most they need to prove is safety.
Only certain variants have been studied against certain vaccines.
Yes we have obviously not tested every combination of vaccine and SARS-CoV-2 variant. But so far, the evidence that we have supports the working assumption that all vaccines drastically reduce, or in some cases eliminate entirely severe COVID-19 symptoms.
I mean, for transparency, we've only tested a very very small subset of the combinations, so it's not very indicative of anything.
The "double mutation" is L452R and E484Q. L452R is the defining feature of the B.1.429 variant (California). E484Q has been seen in derivatives of B.1.429 and in bunches of other variants in the US. It has some antibody evasive properties, but not enough to render vaccines ineffective. Yes, the E484K mutation seen in B.1.351, P.1, and P.2 has been more studied, but E484Q has been studied too.
Double mutant makes it sound like it is something entirely novel that is going to murder us all.
That could mean it's likely the virus is running out of useful mutations?
I've actually seen it referenced as the "triple mutant"!
That is the totality of information.
https://www.washingtonpost.com/nation/2021/05/10/coronavirus...
https://www.biorxiv.org/content/10.1101/2021.05.04.442663v1
I don't have access to the FT article as it is paywalled, but some less meaningful sources have summarized it and use the "modest evading" phrase.
As I don't care for the conversation as I lost all energy going over this stuff last year when the same thing happened, a preprint is not peer reviewed and is necessary to become peer reviewed. Hundreds of thousands of people will die before that happens. Make your own decisions.
This generally means that a pseudovirus built with the mutated spike escapes some monoclonal antibodies and has reduced neutralization titers against convalescent sera, which is fairly normal and doesn't add up to an escape mutation.
When it mutates enough to form an actual escape mutation that will probably come at a cost to the virus for transmissibility/virulence/viral load because it will need to escape at ~20 different epitopes. And still cross reactive T-cells will likely identify the new strain enough and active your immune system to contain it so that it acts more like a common cold than COVID-19.
Booster shots are probably still not a bad idea though, the more it gets boxed in by our immune systems, the more it'll have to make those costly evolutionary choices and become less virulent.
Do you have some sort of medical education or this is a regurgitation of some sources you’ve read as a hobbyist?
I ask this because you seem to talk from a place of authority and fact and i respect that but typically thought of Ycomb as a place comp sci folks usually congregate.
Otherwise, it's easy to find plausible-sounding papers that have failed to reproduce in subsequent studies, that use too low samples compared to similar studies with different conclusions, that were later retracted etc.
Unless you've studied the domain in question in depth, it's not like you could use the citations in any other way. Trust, as a heuristic, is fundamental to advanced research as much as it is for everything else in society.
Meta-studies have found that, depending on the field, up to 70% of published papers can't be reproduced. I'm not sure its possible for considering that a crisis to ever be "overblown".
As to old papers, go back to the 1950’s and plate tectonics was still being debated. What do you think the other geological papers where based on? When you read a specific older paper it’s generally because it stood the test fo time, but that’s just selection bias.
I'm sure it's not your intention, but this phrase might be mistaken for an offensive, negative critique of the OP's abilities, which may make the OP hesitate to respond, or respond defensively.
If you are purely seeking information, without prejudice, then your question would be more effective if you ended it before the 'or'.
Yeah, and they mostly keep their mouths shut except to confirm what everyone is already saying because trying to correct the narrative or dispel a popularly held belief on a site with a voting mechanism is an exercise in futility. Nobody will read your comment when it's dead so why bother.
But, it would be ideal if we could also find proteins on the surface of virus that are less likely to mutate (than other proteins in the virus) that we could teach our immune systems to look for.
Why would evolution select for less virulence in a virus like this? Given covid doesn't rely on symptoms to spread like the common cold seems to, it would seem like the evolutionary pressure would be the opposite. Rather than moderate symptoms, instead jack up viral loads in the host as quickly as possible to spread before the immune system gets involved.
/not a biologist
Every mutation runs the risk of reducing its binding affinity to ACE receptors to get inside cells - or might impede cell entry functions.
Given the amount of infection out there, whatever "easy" mutations might've been available to it clearly haven't been very useful in increasing its rate of spread - and haven't touched anything the vaccines target.
So it's quite likely that whatever needs to happen to evade the vaccines is otherwise deleterious to its virulence.
But it is doing that in response to evolutionary pressure because when a good fraction of the people are recovered or vaccinated then an R0 of 3.0 doesn't work as well when its chasing after those remaining susceptible people.
There'll be an upper limit to how much it can increase its binding to ACE / viral load / R0 though. Once you hit that point infections should fall off a cliff. Then the virus will start to come under pressure to achieve immune escape.
To really achieve immune escape the virus should have to make costly mutations. It shouldn't be able to pick the most optimized spike conformation, it'll have to pick a spike conformation that immune systems don't recognize.
It can't be ruled out that the virus has so much "room" to mutate on the spike protein that high virulence total escape mutants could be formed, but probably not. There are estimated to be 20 epitopes on the spike that the immune system recognizes and to really escape it needs to mutate sufficient to change all of them. Some of them are likely to be expensive to the virus. And if we get booster shots like I said to box it in more, then it should run out of room and start to mutate more towards stealth and less towards virulence.
And there's historical parallels to 1918. At first the H1N1 virus came back in waves that became more virulent. Then once more than half the world had been infected it started to come back as seasonal influenza and spread endemically in humans until 1957. Some of that is likely partial immunity from previously infected individuals, some of that is probably that the virus stated to favor evolving to escape detection and not for virulence and transmissibility.
The H1N1 pandemic is an interesting historical model, and the more deadly later waves indicate that more virulent variants were produced in that pandemic as well. He seems to be arguing that vaccines are causing the variants and that natural herd immunity is better, which is bullshit.
First of all the vaccines are 80-90% effective, even against variants, which greatly reduces the number of people that the vaccine can use to mutate new variants. When there are vaccination failures the vaccines prevent symptoms, prevent viral load and shedding and transmissibility. That cuts down on the production of variants as well.
There's also considerable cross protection in the human immune system since immunity isn't binary like an on/off switch. As a historical example the people born before 1957 were exposed to H1N1 and had cross reactive T-cells to the 2009 H1N1 pandemic. So after mutating in pigs for 50 years the human immune system still recognized the H1 envelope protein sufficiently to take the edge off of that pandemic to make it essentially nothing. And we vaccinated younger people (with I.M. flu vaccines) and didn't see the emergence of hugely virulent H1N1 variants.
The variants are arising now because there's a decreasing fraction of the population which is 100% susceptible to infection and the virus is chasing after that decreasing fraction by increasing transmissibility, viral load and virulence. The vaccines will be effective at taking people out of that 100% susceptible pool even though they're not absolutely perfect. The virus will eventually run out of that 100% susceptible pool and will have to start optimizing for costly immune escape variants which will lower its virulence in order to try to get around vaccinated and recovered individuals immune systems.
This right now, with the evolution of more virulent variants is the WORST time to be playing the natural herd immunity card. Everyone needs to get vaccinated to protect themselves and to put the virus under more pressure to make costlier mutations than it has been able to make so far. Spreading this idea that the vaccines are producing the more lethal variants is literally going to get people killed by having them skip vaccinations and wind up contracting one of the most lethal variants the pandemic is likely to produce. That is optimizing for the worst possible roll of the dice for yourself.
So yeah, he should be banned off of social media and you're killing people by spreading this misinformation.
Cheers.
You're arguing to ban critical thinkers having a conversation, perhaps instead you should be ban off social media for wanting to censor intellectuals/critical thinkers?
Especially since you're seemingly giving a well-thought out response but you immediately admit you skimmed it, and then wrongly claim they're pushing for herd immunity.
You also reference cross immunity, however those weren't using mRNA vaccines afaik, and so the mechanism and spread that the immunity will cover for variants won't be the same.
I was wrong, you're not as rational or thorough of a person I thought you might be based on your initial explanation that I responded to.
When you see articles about antibody evading or antibody escape the research is not dealing in absolutes. It's perfectly possible for there be some antibody escape but the overall immune response is perfectly adequate to quickly deal with an infection.
With the variants of concern so far we've seen a similar pattern, sometimes there can be a reduction in efficacy of the vaccines (remember all efficacy endpoints are measured against preventing symptomatic disease), but at the same time they mostly provide a very high protection against severe disease and hospitalization.
So the two headlines are both perfectly correct, the current variants of concern have the ability to demonstrate antibody escape at a slightly higher rate than the original variant, but the current vaccines still protect people against sever disease.
My understanding is that at this point we don't know yet. The actual testing would probably require a vaccinated person to be exposed to that strain.
Chances are that vaccine is probably still fine.
The real immunity comes from the T cells which will create new antibodies when needed, and may adjust those to variations in the strain.
It’s just a glass half full or half empty statement.
The current hysteria has really opened my eyes in regards to mass media. We all know mainstream reporting is bad in fields we're experts in, but with the many crazy and often self-contradicting things that are currently reported you don't even have to have any expertise to see the problems in the story.
However, a measure of immunity like neutralizing titers isn't a 1:1 function of immunity.
So a simple example (with made up numbers) would be that a particular strain sees a 6x reduction in neutralizing titers compared to the original strain, but it doesn't mean much because there are enough neutralizing titers provided by the vaccine that even a 15x fold reduction would provide strong protection. In this case you could say that the strain has modest antibody evading capabilities AND that the vaccine provides strong protection against it.
I think most media outlets tend to overemphasize the "evasion" angle in headlines, either due to incompetence or for clickbait purposes. Given that almost every single one I've read has a quote from a physician along the lines of "This isn't anything to worry about, it still provides protection" buried a few paragraphs down, I'm assuming its the latter.
https://theconversation.com/new-coronavirus-variant-what-is-...
Mutation causes random changes, the selection process eliminates those that render the mutated version less fit. The focus on the spike is because most random changes to the spike also make it useless, the virus becomes impotent. Such mutations won't thrive of course, and so we hardly see them at all, but they are happening.
In contrast, many random changes elsewhere might not prevent the virus from working. They might say, make it less able to survive outside a body, which would give it a disadvantage against variants that don't have that change, but if they also mean the immune system of a previous host doesn't recognise them, that's a big advantage to counteract that. We see lots of these variants because they "work", but since the spike is the same existing vaccines ought to be effective.
So this is why it made sense to focus on the spike, even though as this article shows it isn't a magical panacea.
[1] A glaring counterexample to your hypothesis is Brazil (Manuas) where prior infections (as high as 60%) didn't stop the P1 variant from ripping through.
Do you have a source for that?
"Natural exposure induces a dominant Ab response against the nucleocapsid protein (NP), but since NP is not in the vaccine, there is no vaccine induced response against it. In this way vaccinated people who had a prior natural exposure can be classified because they have Abs to NP."
Simply looking at one aspect of immunity - detectable antibodies in the blood - is a very incomplete way of looking at the overall level of protection. For example, it's well known that mucosal immunity is important, and injected vaccines have a hard time inducing that kind of immunity: https://theprint.in/opinion/why-a-mucosal-covid-vaccine-has-...
It's also concerning that there is evidence that while people who have been vaccinated are much less likely to be infected. If they do get infected, they are more likely to be infected with one of the variants than unvaccinated: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA728463
The immune response developed to our vaccines is quite specific - they only generate the spike protein - which leads to a much less diverse response than a natural infection.
Finally, the study you quoted can't really compare apples to apples anyway, as it's defining prior infection as simply having some level of antibody response, without considering how mild or severe those infections actually were.
I have not seen an actual credible claim that injectable vaccines can’t produce mucosal immunity. IIRC the HPV vaccines seem to generate strongly protective mucosal immunity. The opinion piece you linked seems off, too: the mRNA vaccines and (possibly to a lesser extent) the viral vector vaccines do seem to prevent most infections.
But it’s definitely true that antibodies in the blood are an incomplete picture. There are also memory B cell and all kinds of T cells.
I'm nowhere near as concerned about a variant infecting my upper respiratory tract as I am with being unvaccinated and having any of the variants attack my heart, kidneys, lungs and blood.
The use of spike was also not a mistake. Attempts to produce vaccines against NP for SARS-CoV-1 produced signs of ADE, so that is why everyone is using spike-only (other than the few inactivated virus vaccines).
That's not "concerning"...it's a truism. You've made those people immune to the wild-type strain. If they're going to get infected, it's going to be to a variant. You're still missing the denominator (i.e. how often does it happen?) and the most important question: how serious is it when they do get infected?
So far, the answers are "not often", and "not serious", respectively.
>Simply looking at one aspect of immunity - detectable antibodies in the blood - is a very incomplete way of looking at the overall level of protection
You seem to have no idea what you are reading. Of course vaccines aren't going to have antibodies against the nucleocapsid -- they only generate antibodies against the spike! The vaccines only ask the human body to develop immunity to the spike!
And you know what actually neutralizes the virus? Mostly antibodies against the spike because that is where all the important parts of infecting a cell originate from.
>For example, it's well known that mucosal immunity is important
You are right about mucosal antibodies -- but your statement is also proving to be false as more research comes out. The latest research shows IgG antibodies from vaccination in the mucosal regions too. Apparently our nose is not just waiting for IgA from a natural infection (https://www.medrxiv.org/content/10.1101/2021.05.06.21256403v...)
>It's also concerning that there is evidence that while people who have been vaccinated are much less likely to be infected. If they do get infected, they are more likely to be infected with one of the variants than unvaccinated
You also completely misrepresented this (and frankly, it's disappointing you couldn't even link to the actual publication -- it's https://www.medrxiv.org/content/10.1101/2021.04.06.21254882v...). The framing of this is disingenuous. Vaccines provide nearly complete protection against the non-variant form of COVID-19. They provide a little less protection against variant COVID-19s. Your non-protected human body is the same way -- it's more likely to get a variant too. It isn't that if you get infected after vaccination, it's because you were more susceptible to variants, it's that everyone is more likely to get one of the variants. Your risk is still minimized way more than than if you weren't vaccinated!
> The immune response developed to our vaccines is quite specific - they only generate the spike protein - which leads to a much less diverse response than a natural infection.
Which tells me that your response of:
> You seem to have no idea what you are reading. Of course vaccines aren't going to have antibodies against the nucleocapsid -- they only generate antibodies against the spike!
is wholly inappropriate as they clearly know what you are using as a rebuttal and makes me wonder if you are the one with no idea of what you are reading!
Perhaps take a second to read the person's comment more thoroughly before being rude, which I see you've continued with in the rest of your comment. It's a discussion, not a fight, try to add your thoughts in a better way, please.
This says nothing about the strength of a previous infection. It very plausibly just says that R > 1.7, ie it is infecting the remaining 40%.
The prior infection estimates for Manaus were simply wrong. They were based on a paper that "adjusted" the observed seroprevalence rates upward by a factor of ~3x. The parsimonious conclusion is that these corrections were too aggressive and ended up over-estimating infections. See Figure 2a in the paper, here:
https://pubmed.ncbi.nlm.nih.gov/33293339/#&gid=article-figur...
It is a "glaring" example only of how the low editorial standards of major journals during this pandemic has led to a wave of confusion amongst the public.
Apparently they're using 40% Astra Zeneca, 60% Sinopharm; hopefully the issue is simply the latter being ineffective. But as all the success stories with vaccination have also had very significant numbers of deaths with covid, we may need significant levels of natural immunity in conjunction with vaccine immunity to actually get cases to decline.
New Zealand had zero community cases without vaccination, during 2021 its vaccination programme has only covered some front line workers and very high risk people, and it still has zero community cases. Is that "success"? Is it "not success" ? How would you tell?
Whereas in my own country about two thirds of adults have had at least one jab, but still people are dying every single day from COVID-19, just much fewer than an the height of the pandemic here. Is that a success? Not a success?
One of the reasons New Zealand was so slow? With zero cases they had no reason to do Emergency Authorization. So they didn't. The Pfizer vaccine they picked got the full (albeit accelerated) approval process that any other medicine would get. This behaviour would be crazy in a country like the US with thousands dying, but it made sense in a country where most citizens have negligible risk day-to-day.
I think you're reading my comment incorrectly. I'm not promoting a criteria. I'm just stating the facts: we may find out that vaccines alone simply can't stop covid from infecting - and maybe even killing - large numbers of people.
Obviously, if that is true to a sufficient degree, lockdown may prove to have been pointless.
> How would you tell?
New Zealand will most likely find out how successful their vaccination program was when they open their borders to the rest of the world.
> The rest had either had a single dose or were unvaccinated.
So ~66% of the cases were from partially or unvaccinated people.
The Seychelles is still 40% unvaccinated. Even people who are vaccinated have some chance of getting infected, though if they get infected, their chance of showing symptoms is lower, and their chance of ending up in the hospital is much lower. It looks like the people testing positive in the Seychelles are mostly unvaccinated, and that the people ending up in the hospital are even more likely to be unvaccinated. But there's not enough information in the BBC article to judge just how effective the vaccines have been in the Seychelles.
The BBC article does contain one falsehood:
> In April, China's top disease control official said the efficacy of the country's Covid vaccines was low, although he later insisted his comments had been misinterpreted.
George Gao did not say this. He gave a talk at a conference on vaccines which was blatantly misconstrued by a "researcher" at an American think tank, the Council on Foreign Relations. That misrepresentation then got spread by the media. All George Gao actually said was that researchers should consider ways of increasing the efficacy of vaccines that have lower efficacy. He didn't name any specific vaccine or any specific country. He proposed the same sorts of measures that are being considered for other vaccines, such as the AstraZeneca shot: delaying the second dose, mixing vaccine doses, etc. This got twisted into an "admission" that Chinese vaccines have low efficacy. It's too bad to see that the BBC is still repeating this false claim, weeks later.
I see 67% effectiveness of preventing symptomatic cases for Sinovac. I'm not sure where the 80% comes from, they could be talking about AstraZeneca.
> A large multi-country Phase 3 trial has shown that 2 doses, administered at an interval of 21 days, have an efficacy of 79% against symptomatic SARS-CoV-2 infection 14 or more days after the second dose.
There are two different Sinopharm vaccines, but I think that BIBP is the one being used in the Seychelles. And yes, as you note, the Phase III studies were conducted outside of China. In order to conduct a Phase III study, there has to be community transmission of the virus, meaning that Phase III trials are impossible in China right now. You would get the same result for the vaccine and placebo arms of the trial: no infections.
1. https://www.who.int/news-room/feature-stories/detail/the-sin...
Seychelles just reported 1800 cases for the last week or 1.8% of its total population. This equates to 6 million cases in the US or more than 800k per day, a number never approached.
> It looks like the people testing positive in the Seychelles are mostly unvaccinated
It stated that 1/3 were in fully vaccinated and the rest were in partially vaccinated or unvaccinated. There are now 60k that are fully vaccinated, leaving just 8.5k first-dose only. The article was written before the 1800 cases dropped a couple days ago.
More data is needed for hospitalizations and deaths, but as it stands now, it does not look convincing for the vaccine. It's likely more cases will continue to come over the next few weeks, even more than the record breaking prior week.
Seychelles and other island nations that had no major covid outbreaks before vaccine launch (only 500 cases prior and 7.5k since) are the best real life settings we have for vaccine efficacy. For much of the rest of the world, a huge number of people were already infected before vaccine launch, making it difficult to separate out the effectiveness of the vaccine.
Covid can wreck havoc on your body and leave it in a weaker state.
Let me change the perspective: when I get the flu because I stupidly did not get the flu shot that year, I don’t rush out and get the flu shot after the fact. I’m wondering why I would do the same with this vaccine when there are lots of evidence that first rounders are not likely to be infected even by variants (assuming low viral load)
The best answer I've heard is: it will give you "extra immunity".
Which begs the follow on question, if we're so concerned about topping off our immunity, why shouldn't people get vaccinated and revaccinated every month or two?
The vaccine produces antibodies to a specific stretch of the spike protein. So everyone who has the Pfizer vaccine has a similar (but not identical) group of antibodies.
Those infected with Covid-19 have a more diverse set of antibodies that may or may not protect as well against varients.
Now, of course the excellent chance of becoming immune to a respiratory infection that's killing loads of people is a much better offer than a Coke. So I agree people should take up this offer, get yourself vaccinated - but we shouldn't claim "literally no downside".
> no downside to receiving the vaccine if you've already had COVID
So I assume that this means that there is no difference in potential unwanted effects between persons who have already had COVID and who have not.
to be fair, you could have scheduled your shot at a different time so the kebab shops would have been open amirite
I honestly hoped I had more side effects! You know you’re not getting sick, so a mild fever? Kind of a perverse pleasure.
Unlike the mRNA platforms, these vaccines use an existing virus to make the spike proteins. Specifically, an Adenovirus (so the sort of thing that might be implicated in some colds) but which ordinarily thrives in Chimpanzees instead of Humans, so they can have confidence you aren't immune to it already. The virus is altered to tell human cells to make the protein chosen by the engineers (for COVID-19 this was the spike protein from the SARS-CoV-2 virus); and not more copies of itself, once the copies in the vaccine injection are cleaned up (typically a few hours to a few days) the virus is gone, so you can't "catch" the virus.
But of course your immune system has no particular reason not to destroy this (harmless) Chimp virus meanwhile, it shouldn't be in your body, so it's every bit as much a target as the spike proteins we want immunity against.
Thus, it's certainly possible any fever one particular patient suffers is a side effect from their immune defence against this poor harmless chimp adenovirus, and nothing to do with SARS-nCOV-2 or its spike protein. No way to tell for sure I believe.
On the other hand, there is some concern around the phenomenon known as "original antigenic sin". Its unknown if it is or will ever be an issue with Covid, but it essentially means that for some viruses (such as the flu), your immune system imprints on a virus the first time it encounters it, and more heavily relies on immunity for that particular virus than new antibodies for variants of that virus later on. This leads to the body mounting a sub-optimal defence against new strains of the virus (which is in part why we have yearly flu vaccines that don't offer amazing protection). There is some concern that there is a possibility that over time covid will continue to mutate and those whose initial infection was natural won't have as protective immunity as those who were vaccinated first, precisely because the vaccine only targets the spike protein and not the entire virus:
"Still, Hensley isn’t worried about imprinting — or at least not among people who have been vaccinated with mRNA vaccines. The very strong immune response generated by the Moderna and the Pfizer-BioNTech vaccines should override any imprinting impacts as SARS-2 mutates, he said. Hensley worries, though, that people whose immunity to the virus comes from infection, not vaccination, might have more difficulty handling variant viruses because of imprinting effects.
David Topham, an immunologist at the University of Rochester Medical Center and director of the New York Influenza Center of Excellence, also envisages that possibility.
He noted that, in the earliest stages of SARS-2 infection, the immune system mounts a response to a portion of the spike protein called S2. Later, the immune system focuses its attention on other parts of the spike, notably the part of the protein that attaches the virus to cells it invades, known as the receptor binding domain.
It’s not yet known if the early focus on S2 — which doesn’t change much from virus to virus — will blind the immune system to the changes elsewhere in the spike protein, the changes updated vaccines would be trying to teach the immune system to respond to, Topham said.
Topham doesn’t think this will be a problem in vaccinated people, because of the way the vaccines in use have been designed. The spike proteins they trigger production of appear to hide the S2 region, he said. The immune system can’t fixate on something it doesn’t see.
For people whose immunity comes from infection, Topham sees three possible scenarios. “It can be a problem, because the immune cells specific for S2 outcompete immune cells against other components of the spike protein that you really need in order to get protection. It can be inconsequential in that eventually the responses to the other parts of the protein catch up and it doesn’t matter. Or it could actually be a benefit because it gets the immune system revved up more quickly.”[0]
[0] https://www.statnews.com/2021/04/16/next-generation-covid-19...
https://www.cnbc.com/2021/05/11/india-covid-explainer-what-w...
The reality is that vaccines target multiple proteins and one protein mutation usually does not even evade that specific protein from matching (much).
It's a sliding bumpy scale with each mutation reducing the effectiveness of the vaccine some small random amount.
It's very likely that all the current vaccines confer sufficient immunity to all current variants to a degree that will prevent serious Illness and likely even transmissibility.
But the real takeaway here is that, like flu, we are looking at yearly covid boosters for everyone for years to come.
If it protects against the 2 least significant variants, that's less interesting of an article.
Unless it protects against all variants the headline would likely be inaccurate without the "worrying" qualifier.
I could agree with a criticism that "worrying" should be replaced with a better identifier of the specific variants being discussed, but I don't have a replacement proposal. And dropping the word "worrying" seems like it might be factually wrong (it also might not be, I don't know)
Depending on what you mean by “mRNA instructions” that might not be the case. Both vaccine mRNAs encode exactly the same variant of the spike protein.
Not technically, it’s actually the same protein/polypeptide sequence in both cases, 100% identical, including the proline mutations that stabilize the prefusion conformation. You can check that easily by translating and aligning in silico both coding RNA sequences.
> the way it was optimized differs (not by much but it’s different)
I’m assuming that you’re referring to the codon optimization step that the RNA sequences underwent. While both coding sequences were optimized differently, this has no effect on the final protein product.
So far I haven’t seen conclusive information about mixing the vaccines, but I think that will be the reality for booster shots late this year/early next year in the UK.
From what I heard, in normal circumstances is even recommend to give a booster vaccine shot from a different manufacturer.
https://github.com/NAalytics/Assemblies-of-putative-SARS-CoV...
I’m not gonna go into how the virus was sequenced or what the process to generate the vaccine was, but in this case, I believe your claim of being 100% identical is wrong.
I already stated that both coding RNA sequences are different. It is their product, the protein sequence, that is 100% identical in both sequence and structure. The protein that, as you mentioned, is presented as an antigen to the immune system.
If you don’t believe me, and since you already found the FASTA mRNA sequence (or, more specifically, its cDNA equivalent) for both vaccines, you can translate[1] each spike protein RNA section and then align[2] both translated protein sequences.
This is what you get:
#=======================================
#
# Aligned_sequences: 2
# 1: Pfizer
# 2: Moderna
# Matrix: EBLOSUM62
# Gap_penalty: 10.0
# Extend_penalty: 0.5
#
# Length: 1273
# Identity: 1273/1273 (100.0%)
# Similarity: 1273/1273 (100.0%)
# Gaps: 0/1273 ( 0.0%)
# Score: 6727.0
#
#
#=======================================
Pfizer 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHS 50
||||||||||||||||||||||||||||||||||||||||||||||||||
Moderna 1 MFVFLVLLPLVSSQCVNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHS 50
Pfizer 51 TQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNI 100
||||||||||||||||||||||||||||||||||||||||||||||||||
Moderna 51 TQDLFLPFFSNVTWFHAIHVSGTNGTKRFDNPVLPFNDGVYFASTEKSNI 100
...
Pfizer 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSC 1250
||||||||||||||||||||||||||||||||||||||||||||||||||
Moderna 1201 QELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIMLCCMTSCCSCLKGCCSC 1250
Pfizer 1251 GSCCKFDEDDSEPVLKGVKLHYT 1273
|||||||||||||||||||||||
Moderna 1251 GSCCKFDEDDSEPVLKGVKLHYT 1273
Lots of people call all kinds of skewers Doner Kebab even though that's incorrect.
It's speech and sometimes it doesn't fit our nice rules.
The only people who call them that are at least 50. Everyone I know except my grandmother calls them tissues. Things change. Shit happens.
You mean the company that scaled up production to hundreds of millions of doses, ran clinical trials in dozens of countries for tens of thousands of patients, put together all the regulatory documentation for dozens of countries, including negotiations with regulators, then developed a worldwide logistics system to get the vaccine where it's needed. And did all that with few stumbles in less than a year.
So yeah, they are "just the manufacturer".
As for Pfizer, they do nothing at all for me in Hong Kong, see ?
Pfizer did: 1) scaled up production to hundreds of millions of doses, 2) ran clinical trials in dozens of countries for tens of thousands of patients, 3) put together all the regulatory documentation for dozens of countries, including negotiations with regulators, 4) then developed a worldwide logistics system to get the vaccine where it's needed, including to local distributors like Fosun.
Production is a multi-step process involving both Pfizer and BioNTech.
https://en.wikipedia.org/wiki/Pfizer%E2%80%93BioNTech_COVID-...
The government description seemingly tries to credit Fosun with its development: "mRNA technology platform - by Fosun Pharma in collaboration with the German drug manufacturer BioNTech" [1]
On the plus side, HK is one of the few places in the world where anyone aged 16 or over can currently get their choice of free vaccine (BioNTech or Sinovac) at a nearby vaccine center in about 20 minutes with a booking delay of a couple of days (for defrosting).
Unfortunately, few seem to want it, with bookings running at about 10k/day despite 40k/day capacity for BioNTech alone.
https://www.pfizer.com/news/hot-topics/why_pfizer_opposes_th...
Specifically this section:
Which brings me to the second question. Is the proposed waiver going to improve the supply situation or create more problems? And my answer is categorically the latter.
But I'm a tad annoyed that they pronounce it "Bion-Tech" rather than "Bio-N-Tech", the latter was the intended pronunciation by the owners, I think.
>Pfizer Covid vaccine protects against worrying coronavirus variants
It reads as: "Don't be worried, Pfizer has the variant problem solved."
That’s really reading a lot into what is a simple, concise, factual headline. There are a set of currently-worrying variants (about which there had been much public concern about the effectiveness of current vaccines), and the Pfizer vaccine is effective against them.
That headline is very much not a “Mission Accomplished” banner.