7 ms·

I think the title should say that, but they did so some (very very limited) human research: >For proof of principle purposes, 5 co-authors of this report volun

I think the title should say that, but they did so some (very very limited) human research: >For proof of principle purposes, 5 co-authors of this report voluntarily took an intranasal spray of Ad5-S-Omicron that was prepared for clinical trial. They then tested for immune response in "nasal lavage fluids," which apparently is the fluid collected after flushing out a test subject's nose with a saline solution, against the virus' spike and a psuedovirus. I don't know how the results in lavage fluids compares to similar neutralization studies they do for other kinds of vaccines, except that they also use psuedovirus sometimes.

timr 3y ago
From a high level, the types of immunity seen in the nasal mucosa are completely different than the blood samples used for other kinds of vaccines. You'd expect to see antibodies in the mucosa. The only saving grace of the existing vaccines is that the T/B-cell response induced is long-lasting and protective. Antibody response is a proxy for what you really care about (survival), and it's a crappy proxy for that, because antibodies rise and fall quickly even if your immune system is well-prepared for future exposures. The traditional problem with nasal vaccines is that they induce a quick spike in antibodies in the mucosa, which then go away without the corresponding long-term rise in cellular immunity that is seen with injected vaccines.
- actuallyalys 3y ago
  That's helpful context, thanks! I assume the four-week follow-up they did would still be within the window of that "quick spike" you're mentioning?
  - timr 3y ago
    Yes.
- htss2013 3y ago
  >The traditional problem with nasal vaccines is that they induce a quick spike in antibodies in the mucosa, which then go away without the corresponding long-term rise in cellular immunity that is seen with injected vaccines. Are you talking about traditional vaccines or mrna ones for covid? Because aside from mucosa it sounds like you're describing the short term durability of mrna vaccines that need to be perpetually redosed months not years later. If that's the baseline, what is there to lose by adding or replacing them with short term mucosal immunity?
  - lamontcg 3y ago
    They're talking about the B-cells and T-cells created by the injected mRNA vaccines, which are certainly more or less permanent, and always waiting to be activated on any future infection. Those are what prevent severe disease, but they don't prevent infection. The protection against severe disease from a 3-shot series of the mRNA vaccine is in all likelihood completely permanent. For the nasal vaccines to fail to produce that cellular immunity would be a massive failure. The short term durability of neutralizing antibodies seen with EVERY SARS-COV-2 VACCINE NOT JUST THE MRNA ONES is likely a feature of immunity to respiratory viruses. The "one series of shots to never contract the disease again in your lifetime" style of immunity probably doesn't exist for this virus. Certainly we don't know how to create one right now.
  - timr 3y ago
    Traditional vaccines of any sort. The kind you inject, and don't inhale. > Because aside from mucosa it sounds like you're describing the short term durability of mrna vaccines that need to be perpetually redosed months not years later. So...it's worth saying this out loud: we have no absolutely no good evidence that we need to keep re-dosing these vaccines. None. The bi-valent booster was approved based on a trial with a handful of mice. Do these vaccines improve outcomes in young people? We have no idea. People who have had Covid? No idea. Old, sick people with 5+ prior doses? We can maybe guess, but we don't know. There's no data. I'm not exaggerating. It's an absolute embarrassment that the FDA keeps approving these shots without proper trials. It's all a nasty stew of partisan politics, financial incentives, and "science" so bad that it wouldn't pass muster at a high-school science fair. Anyway, point is that you can't conclude anything scientific from the mRNA Covid vaccine dosing schedules, since they're fundamentally not scientific. The best science we have suggests that the initial two-dose series provided long-lasting cellular immunity.
    - buck4roo 3y ago
      There are multiple indicators that the currently available vaccines probably are three dose vaccines. But time and trials will tell.
    - chimprich 3y ago
jxramos 3y ago
interesting netti pot effluent, that's a very fascinating fluid to work with and subject to focus diagnostics against. I'm pretty impressed.
- TylerE 3y ago
  It's considerably less unpleasant than other methods of sampling.

timr 3y ago

From a high level, the types of immunity seen in the nasal mucosa are completely different than the blood samples used for other kinds of vaccines. You'd expect to see antibodies in the mucosa. The only saving grace of the existing vaccines is that the T/B-cell response induced is long-lasting and protective. Antibody response is a proxy for what you really care about (survival), and it's a crappy proxy for that, because antibodies rise and fall quickly even if your immune system is well-prepared for future exposures. The traditional problem with nasal vaccines is that they induce a quick spike in antibodies in the mucosa, which then go away without the corresponding long-term rise in cellular immunity that is seen with injected vaccines.

actuallyalys 3y ago
That's helpful context, thanks! I assume the four-week follow-up they did would still be within the window of that "quick spike" you're mentioning?
- timr 3y ago
  Yes.
htss2013 3y ago
>The traditional problem with nasal vaccines is that they induce a quick spike in antibodies in the mucosa, which then go away without the corresponding long-term rise in cellular immunity that is seen with injected vaccines. Are you talking about traditional vaccines or mrna ones for covid? Because aside from mucosa it sounds like you're describing the short term durability of mrna vaccines that need to be perpetually redosed months not years later. If that's the baseline, what is there to lose by adding or replacing them with short term mucosal immunity?
- lamontcg 3y ago
  They're talking about the B-cells and T-cells created by the injected mRNA vaccines, which are certainly more or less permanent, and always waiting to be activated on any future infection. Those are what prevent severe disease, but they don't prevent infection. The protection against severe disease from a 3-shot series of the mRNA vaccine is in all likelihood completely permanent. For the nasal vaccines to fail to produce that cellular immunity would be a massive failure. The short term durability of neutralizing antibodies seen with EVERY SARS-COV-2 VACCINE NOT JUST THE MRNA ONES is likely a feature of immunity to respiratory viruses. The "one series of shots to never contract the disease again in your lifetime" style of immunity probably doesn't exist for this virus. Certainly we don't know how to create one right now.
- timr 3y ago
  Traditional vaccines of any sort. The kind you inject, and don't inhale. > Because aside from mucosa it sounds like you're describing the short term durability of mrna vaccines that need to be perpetually redosed months not years later. So...it's worth saying this out loud: we have no absolutely no good evidence that we need to keep re-dosing these vaccines. None. The bi-valent booster was approved based on a trial with a handful of mice. Do these vaccines improve outcomes in young people? We have no idea. People who have had Covid? No idea. Old, sick people with 5+ prior doses? We can maybe guess, but we don't know. There's no data. I'm not exaggerating. It's an absolute embarrassment that the FDA keeps approving these shots without proper trials. It's all a nasty stew of partisan politics, financial incentives, and "science" so bad that it wouldn't pass muster at a high-school science fair. Anyway, point is that you can't conclude anything scientific from the mRNA Covid vaccine dosing schedules, since they're fundamentally not scientific. The best science we have suggests that the initial two-dose series provided long-lasting cellular immunity.
  - buck4roo 3y ago
    There are multiple indicators that the currently available vaccines probably are three dose vaccines. But time and trials will tell.
  - chimprich 3y ago

jxramos 3y ago

interesting netti pot effluent, that's a very fascinating fluid to work with and subject to focus diagnostics against. I'm pretty impressed.

TylerE 3y ago
It's considerably less unpleasant than other methods of sampling.