What makes them new and different is that instead of growing a lot of virus and killing it, or growing a lot of spike protein and purifying it, and using that as the basis for a vaccine, the mRNA prompts some cells to make spike protein.
The adenovirus vaccines are very similar, but use an engineered virus instead of raw (well, encapsulated in a tiny ~plastic bag) mRNA to do that.
It’s a really neat idea. Very clean. But what it presents the immune system isn’t especially novel.
One thing that was novel is that they “broke” the spike protein slightly. The natural one has an open form and a closed form. And the open form is what actually attaches to your cell receptor, so the closed form can possibly evade the immune system. The version coded by the mRNA vaccines doesn’t close, so the “active” part is exposed to the immune system. And there were thought to be limits on how much that active part could mutate and still work.
But it seems that nature was clever, and the spike mutated anyway, and works even better than before.
It may be true that the vaccine can confer better immunity than a very mild case. But most studies have found that infection-induced immunity is better than a dose or two of vaccine, and pretty much every study that’s looked at hybrid immunity (from both a vaccine and a breakthrough case, or a case followed by vaccination) is better than a vaccine alone.
I mean, it’s worse in that not everyone who catches covid recovers. And some who recover have long-term damage. The vaccine is way safer. But those who DID fully recover from a case of covid have decent immunity as a result.
So I’m pretty sure that comments in the press about vaccines still working refer to protection from serious illness, and don’t mean that the vaccine protects better than s prior case does from symptomatic illness.
I thought the spike protein was the delivery mechanism, and not the virus itself. The mRNA vaccines elicit an immune response that targets anything using that spike protein as the delivery mechanism.
A traditional vaccine works just like the immunity you get from prior infection: your immune system recognizes the disease itself and remembers how to fight it.
This is my rudimentary understanding, corrections welcome.
From the New York Times COVID email newsletter today:
How often can I be infected?
Early on in the pandemic, experts thought that immunity from vaccination or previous infection would forestall most reinfections. The Omicron variant dashed those hopes. Some scientists now fear that the future of Covid may include infections two, maybe three times a year, my colleague Apoorva Mandavilli reports.
The central problem is that the virus has become more adept at reinfecting people. Already, those infected with the first Omicron variant are reporting second infections with the newer versions of the variant — BA.2 or BA2.12.1 in the U.S., or BA.4 and BA.5 in South Africa.
Those people may go on to have third or fourth infections, even within this year, researchers told Apoorva.
“The virus is going to keep evolving,” said Juliet Pulliam, an epidemiologist at Stellenbosch University in South Africa. “And there are probably going to be a lot of people getting many, many reinfections throughout their lives.”
I mean, right … but this is just like rhinoviruses, enteroviruses, and scores more.
Are they saying that basically we’re living in a virtual “Groundhog Day” circa March 2020 forever more? That for all intents and purposes, our collective immune system is ever naïve to COVID? That SARS-CoV-2 will always be especially dangerous to humankind, no matter what, no matter when?
I don’t have the science or the data to back it up … and yet: I find that hopelessness very hard to accept. There’s something they’re missing, or not saying. Or getting filtered out in the popular media. Things are not as they’re saying they are … not completely.
This is precisely why they chose to make the spike protein for the vaccine. They thought it was either less likely to mutate, or that if it mutated very much, it might not cause Covid anymore, because the spike protein is the key to get inside our cells.
The spike protein is a part of the virus. It sticks out, and acts as a key to get into our cells. If it changes very much, it might not work as a key anymore, and if so, the virus would become pretty much harmless because it can only reproduce inside our cells.
I think they’re saying it will be a bit like influenza, and also a bit like the common cold. Sort of the worst of each.
Covid can be severe, and deadly, like influenza.
Severity of illness will depend on the variants that are circulating, like with influenza. Vaccines might be a good or less good fit for those variants, and the same with prior infection.
There’s more likelihood of catching it than influenza, like the common cold. And like with a cold, prior infection won’t likely confer lasting immunity, so people can get infected multiple times per year.
But the whole point of the mRNA vaccines is that they give you immunity without ever exposing you to any viral material at all. If the spike protein is part of the virus, then the mRNA vaccines do expose you to viral material, right? Namely, the spike protein viral material.
What is the viral material they’re saying you’re never exposed to with an mRNA vaccine? And how is that different from the spike protein you are exposed to?
Well, I think they are saying its not viral material, I guess, because it was made by your cells, and was never part of any actual virus. But it is the protein (or one form of it) that is found on the surface of SARS-CoV-2.
Our immune systems can recognize a pathogen in multiple ways. Recognizing a surface protein is one way. The spike protein is one surface protein.
People vaccinated with the mRNA vaccines, who have not had Covid and who have developed antibodies, will have antibodies based on the spike protein, but no other part of the SARS-CoV-2 virus. People who’ve had Covid will have additional antibodies based on other parts of the virus. People who’ve only been vaccinated will only have been exposed to the reproduced piece of the virus.
I don’t know where you get that idea from. To develop immunity you need to train your immune system to recognize and neutralize an attacking virus. We do this by exposing the immune system to part of (or all of) the infectious agent in a way that does not cause disease.
Some parts of the virus are more recognizable than others. In the case of COVID-19, it is the spike protein, which is also responsible for mediating viral entry to a cell for infection. We know that for many viruses, it is surface antigen antibodies that are mainly responsible for immunity. However, some viral infections do require an immune response to both a surface and a core antigen for complete immune response. Hepatitis B is one example that requires multiple antigens to clear infection. Immunological assays early in the COVID-19 pandemic identified antibodies to the spike protein as a primary response to infection. So it wasn’t just chosen at random - it was the logical primary target for any vaccination.
Once suitable protein targets for a vaccine have been identified, production of the target protein is the next challenge. If you can find a benign virus similar enough to the infectious agent (such as cowpox vs smallpox) you can use that. You could breed generations of the virus, hoping to find one that is weaker than the original virus - this is the so-called attenuated viral vaccines (such as polio). You can grow viruses and then inactivate them with chemical or radiological treatments, leaving inactive shells. Any method that starts with or relies on live virus has some problems - finding a suitable growth medium for the raw materials, and making sure that the virus does not change in some way (reversing attenuation or resisting inactivation).
With modern genetic engineering techniques, it became obvious that with some gene splicing, it was easy to insert the DNA for a protein into a suitable host (a yeast or bacteria) and get that host to churn out copies. Then you have to just purify the target protein - we know how to grow and manage yeast. Other processes use plants or cells from moths. You can even use larger chunks of DNA to build whole viral shells that have everything except the viral DNA needed for replication.
However, the cellular machinery present in yeast and other cells still isn’t exactly like the human ribosome. So why can’t we use that? Practically, because it is hard to grow human culture cells in bulk. But if you give a human cell some simple instructions (which is what a virus actually does) it can build those parts - no problem. So researchers learned to use a harmless human adenovirus to insert DNA or RNA into a cell to build a protein. This is the basis of the Oxford/AstrZeneca Covid-19 vaccine. The adenovirus itself cannot infect a cell or replicate - it can only insert the spike protein DNA into the target cells to make spike proteins.
Finally, the mRNA vaccine researchers figured out a way to get mRNA directly into a cell - it’s just code for the protein, and once it is in, the cell will follow the instructions until the recipe falls apart in a couple of days. And then it is gone, but the immune system still knows about the spike protein and will continue to respond to it.
In summary - the spike protein was the easiest and best target for initial vaccines. We still don’t know it other antigen targets from the virus are worth investigating - there doesn’t seem to be much good evidence, and I don’t know if there is currently enough for Pfizer/Moderna/etc to invest more millions in adding to the current vaccine. I hear that Moderna seem to be close to an Omicron-specific vaccine, but last I heard Pfizer was back to the lab as the benefits of the new vaccine over the initial vaccine was not sufficiently compelling.
In the same way, some of the late-comers (including those with a full-virus inactivated vaccine like Valneva) are struggling to make headway, which I do not think would be the case if their product was substantially more effective than the existing vaccines, particularly against current variants.
I still don’t understand this quoted claim, or how it relates to your post. Are you saying that you do get exposed to viral material when you get an mRNA vaccine?
From the page you linked, which has that quote, later it says this:
They are, as I said, distinguishing between a piece that was once part of a whole virus, or the virus itself (“viral material”), versus a protein that matches the virus’s spike protein, manufactured inside your own cells (not “viral material”). It’s not written very well – it’s confusing how it’s worded – but I think it’s pretty clear that’s what they mean.
Yes, very simplistically the “spike protein” is the bit of the virus that allows it to attach to cells and gain entry to it. Once in it can do its replicating and cause the cell damage.
The mRNA vaccines don’t teach the immune system to recognise and attack the whole virus, instead they use just the part that codes for the spike protein. This is introduced to the body, the body replicates the spike protein, the spike protein is not dangerous by itself but it does give the immune system chance to learn and respond to it so that when the spike protein appears as a part of the actual virus it can be attacked quickly.
So with an mRNA vaccine the body doesn’t experience the actual, full “viral material” as such, in that it doesn’t get to see the bit of the virus that causes the damage but it does get to see one small part of it, so technically I can see why someone might consider that “viral material” as well.
When the vaccines were developed, they thought the spike protein would be more stable than other surface proteins. There was some surprise when some of the successful variants showed up with multiple changes to the spike protein.
We’d really need an experienced epidemiologist to address, but:
What confounds me is that it would seem like the spike protein could only change so much before it lost the ability to grab onto/infect human tissue. Instead, the spike protein mutates like mad and gets even more infectious. Has any other human pathogen – ever – shown the ability to mutate their latch-on “devices” that gainfully?
One of the things that has given me solace throughout the pandemic to date is that in the end, SARS-CoV-2 would still be a virus. It would act like a virus is expected to act and have limitations similar to all other known viruses. I mean, we’d still have to research and learn SARS-CoV-2’s specifics, yes – but that SARS-CoV-2 would eventually run up against whatever rules and limits all other viruses work under.
Epidemiology, for the moment, seems beat back by SARS-CoV-2. In some ways, it’s not merely a novel virus, but a novel biological entity. However, I refuse to believe that SARS-CoV-2 is biologically “magic” and will continue to successfully counter whatever science throws at it for the rest of time. We’ll beat it. I don’t know how – it may happen all by itself via a natural mechanism we don’t see coming – but we’ll beat it.
Well, I don’t think we can say, “Instead, the spike protein mutates like mad and gets even more infectious.” (My bold.)
Rather, I think, we have an unusual situation where there are so many people infected, and so many (globally) infected people remaining sick for long periods of time, that loads of mutations are having the chance to show up. Naturally, we don’t see the unsuccessful ones much if at all, because they are unsuccessful. The ones that are an “improvement” on the original spike protein or other aspects of transmissibility outcompete other strains and become dominant. It’s pretty textbook evolution, it seems to me.
One thing I’m mildly concerned about is that the vaccines which target the spike protein could inadvertently target the similar spike protein that is on our normal cells. The COVID virus gets into our cells because its spike protein is able bind to the place on our cells which accepts that kind of spike. But then what about the spikes that we have on our normal cells that the COVID virus is mimicking? Will our body start to think that our normal spikes are also foreign invaders and start attacking them?
I cop to bowdlerizing. Everything you posted is certainly understood.
Specifically on the part I just pull-quoted from you:
Surely that kind of thing has happened many times throughout human history. What kept the viruses that (say) cause polio and smallpox from running through mutations and hitting upon something that escaped vaccine-induced immunity?
For that matter, what the heck happened to SARS-CoV-1?
This is going to happen whenever a disease organism is not optimally adapted to infecting human cells. And since SARS-CoV-2 is originally a bat virus, it obviously isn’t. So during the many infections, it’s reproduced trillions (if not quadrillions) of times and probably billions of variations of the spike protein have been produced. The vast majority of those spikes are less efficient at invading human cells and you never hear about them. But a few are better. Those few out-reproduce the strain they come from and become the new dominant strain.
As for whether this has happened before, yes it’s certain it has. I’m afraid I don’t know the details of other diseases enough to cite examples.
