The article I summarize here goes over some of the specific bad vaccine reactions for SARS-1. I expect similar challenges for SARS-2.
Briefly:
In situations where someone took the vaccine, then gets infected by the contagion, they can have a bad reaction where the course of the disease is more severe than if they had not been vaccinated at all.*
Here’s some of what we know about those bad reactions**
Th-2 type immune activation definitely happens
This is an allergy-like immune response
Th-2 reactions happen in severe cases of COVID-19 generally
There might also be a bad complement system related reaction
Complement system means protein complexes that kill cells by poking holes in membranes
Antibody Dependent Enhancement (ADE) might be possible, but is not likely
This is when imperfect antibodies are used as an anchor for the virus to infect white blood cells.
UPDATE: A related thing now strikes me as somewhat likely. It might be fusing with some white blood cells (at least T-cells) and ordering them to apoptose (activate cell-death). Article, h/t CellBioGuy.
* Going off of some other bits of research on this, these individuals probably have lower virus-titer, but higher severity and lethality. A damaging immune response, basically.
** Which vaccine types cause this bad reaction? For SARS-1, any whole-S-protein vaccines were more prone to this bad reaction. Some smaller S-protein fragments didn’t have this issue, hopefully the same fix works for SARS-2. I heard of at least one case where an N-protein-only vaccine attempt also resulted in the Th-2 reaction, though. It’s not totally clear how to avoid triggering it.
So maybe the speed-up you really want is to vaccinate, then deliberately expose to the live virus, and monitor what happens?
This is the type of test I’d rather we do on animal models than humans, to be frank. It seemed that you could test this phenomenon just fine with SARS-1 in animal models.
Thank you, this is the sort of answer I was looking for- I’d naively had the prior that “no effect” was the only non-negligible possibility besides “positive effect”.
I’m normally on team “the FDA is making everything too slow,” but in this case I actually think there’s good reason to be really careful with those Phase-1 vaccine development trials. You don’t need to be using a live vaccine to actively make things worse!
How long does testing for this problem actually take? I’m not sure.
If we were sure this was the only thing we needed to worry about (but I don’t think that it is)… getting a line of evidence where some vaccine takers are exposed deliberately some time after vaccination could maybe speed up weeding out vaccines that trigger worse Th-2 reactions. But if it turned out that time-since-vaccination or current antibody-titer are major factors underlying outcome, we may genuinely need the full period of safety-testing.
And asking people to deliberately expose themselves doesn’t strike me as a… safe cheap or easy thing to do.
This looks like a complicated immune effect, and it seems to be under-characterized. Overall, it looks hard to test in-vitro or in cell culture. I’m pretty sure you’d need animals or humans to do it. I’m not sure which is faster.
Informed volunteers would be heroes, but I think there are enough heroes to make vaccines available months sooner and to save millions of lives. At least it should be in the Overton window to ask for a voluntary trial with the understanding that there’s substantial risk.
While we should at least ask and assess that question...
Yes, it would be good to rule out those things that we do know to expect. And I think animal results* could check this one somewhat. But corners are already being cut, and I still expect some degree of surprises.
I do feel like there’s a lot we don’t know with this virus. I don’t know that the problems will be limited to the things we currently know to look for, and I’d be a little surprised if timing was not at least a bit of an influencing factor.
* Apparently they haven’t found/developed an easy animal that catches the virus, but they are doing animal testing in parallel to check the type of immune response? And the vaccine test result with the 4 macaques at least seemed promising, now up by another 10 macaques tested with that same inactivated-virus vaccine.
While it definitely helps that we have some experience with SARS-1, we can’t totally rely on what we know about SARS-1 and trust that it’ll apply to SARS-2.
(I think SARS-1 and SARS-2′s genetic similarity was said to be only ~80%? This is about as much as we share in common with cows. There can be meaningful differences between the two.)
Here’s just one example. Did you see the “UPDATE” I added to my answer above? Says something like “Oh hey, I guess it probably does make immune cells apoptose?” SARS-1 doesn’t do that thing. As in, the article specifically mentions that they tried with SARS-1 and SARS-2, and only SARS-2 gets into T-cells like this. And they weren’t sure which receptor was responsible.
It’s great to see a lot of science happening on this, but it’s also something of a marker of our vast uncertainties paired with its high priority.
The article I summarize here goes over some of the specific bad vaccine reactions for SARS-1. I expect similar challenges for SARS-2.
Briefly:
In situations where someone took the vaccine, then gets infected by the contagion, they can have a bad reaction where the course of the disease is more severe than if they had not been vaccinated at all.*
Here’s some of what we know about those bad reactions**
Th-2 type immune activation definitely happens
This is an allergy-like immune response
Th-2 reactions happen in severe cases of COVID-19 generally
There might also be a bad complement system related reaction
Complement system means protein complexes that kill cells by poking holes in membranes
Antibody Dependent Enhancement (ADE) might be possible, but is not likely
This is when imperfect antibodies are used as an anchor for the virus to infect white blood cells.
UPDATE: A related thing now strikes me as somewhat likely. It might be fusing with some white blood cells (at least T-cells) and ordering them to apoptose (activate cell-death). Article, h/t CellBioGuy.
* Going off of some other bits of research on this, these individuals probably have lower virus-titer, but higher severity and lethality. A damaging immune response, basically.
** Which vaccine types cause this bad reaction? For SARS-1, any whole-S-protein vaccines were more prone to this bad reaction. Some smaller S-protein fragments didn’t have this issue, hopefully the same fix works for SARS-2. I heard of at least one case where an N-protein-only vaccine attempt also resulted in the Th-2 reaction, though. It’s not totally clear how to avoid triggering it.
So maybe the speed-up you really want is to vaccinate, then deliberately expose to the live virus, and monitor what happens?
This is the type of test I’d rather we do on animal models than humans, to be frank. It seemed that you could test this phenomenon just fine with SARS-1 in animal models.
Thank you, this is the sort of answer I was looking for- I’d naively had the prior that “no effect” was the only non-negligible possibility besides “positive effect”.
I’m normally on team “the FDA is making everything too slow,” but in this case I actually think there’s good reason to be really careful with those Phase-1 vaccine development trials. You don’t need to be using a live vaccine to actively make things worse!
How long does testing for this problem actually take? I’m not sure.
If we were sure this was the only thing we needed to worry about (but I don’t think that it is)… getting a line of evidence where some vaccine takers are exposed deliberately some time after vaccination could maybe speed up weeding out vaccines that trigger worse Th-2 reactions. But if it turned out that time-since-vaccination or current antibody-titer are major factors underlying outcome, we may genuinely need the full period of safety-testing.
And asking people to deliberately expose themselves doesn’t strike me as a… safe cheap or easy thing to do.
This looks like a complicated immune effect, and it seems to be under-characterized. Overall, it looks hard to test in-vitro or in cell culture. I’m pretty sure you’d need animals or humans to do it. I’m not sure which is faster.
Informed volunteers would be heroes, but I think there are enough heroes to make vaccines available months sooner and to save millions of lives. At least it should be in the Overton window to ask for a voluntary trial with the understanding that there’s substantial risk.
While we should at least ask and assess that question...
Yes, it would be good to rule out those things that we do know to expect. And I think animal results* could check this one somewhat. But corners are already being cut, and I still expect some degree of surprises.
I do feel like there’s a lot we don’t know with this virus. I don’t know that the problems will be limited to the things we currently know to look for, and I’d be a little surprised if timing was not at least a bit of an influencing factor.
* Apparently they haven’t found/developed an easy animal that catches the virus, but they are doing animal testing in parallel to check the type of immune response? And the vaccine test result with the 4 macaques at least seemed promising, now up by another 10 macaques tested with that same inactivated-virus vaccine.
While it definitely helps that we have some experience with SARS-1, we can’t totally rely on what we know about SARS-1 and trust that it’ll apply to SARS-2.
(I think SARS-1 and SARS-2′s genetic similarity was said to be only ~80%? This is about as much as we share in common with cows. There can be meaningful differences between the two.)
Here’s just one example. Did you see the “UPDATE” I added to my answer above? Says something like “Oh hey, I guess it probably does make immune cells apoptose?” SARS-1 doesn’t do that thing. As in, the article specifically mentions that they tried with SARS-1 and SARS-2, and only SARS-2 gets into T-cells like this. And they weren’t sure which receptor was responsible.
It’s great to see a lot of science happening on this, but it’s also something of a marker of our vast uncertainties paired with its high priority.