9 ms·

>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-te

by 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
  > We can maybe guess, but we don't know. There's no data. Nonsense. We have data that shows vaccine effectiveness wanes with time. We know boosters improve immunity. We've been giving out bivalent booster for over a year and we have data that they're effective. > I'm not exaggerating. [...] "science" so bad that it wouldn't pass muster at a high-school science fair. You are exaggerating. You're engaging in hyperbole that's an embarrassment to yourself. Armchair scientists should leave the medical decisions to the professionals.
  - timr 3y ago
    > We have data that shows vaccine effectiveness wanes with time. No, we don't. We have confounded, poorly controlled observational studies, and extrapolation from antibody titres. > We know boosters improve immunity. No, we don't. The necessary studies have never been done. Increasing antibodies for a while (in mice) does not equal "improving immunity" in humans. > We've been giving out bivalent booster for over a year and we have data that they're effective. Well, if you say so. But actually...no. Or you'd cite it, instead of just asserting things. > Armchair scientists should leave the medical decisions to the professionals. Such as Paul Offit, FDA VRBPAC member, co-creator of the Rotavirus vaccine, and director of the vaccine education center at the Children's Hospital of Philadelphia? https://time.com/6246525/bivalent-booster-not-very-effective-paul-offit/ https://time.com/6246525/bivalent-booster-not-very-effective... https://www.nejm.org/doi/full/10.1056/NEJMp2215780 https://www.nejm.org/doi/full/10.1056/NEJMp2215780 > In his perspective piece, Offit cites data from two leading virologists—Dr. David Ho, director of the Aaron Diamond AIDS Research Center at Columbia University, and Dr. Dan Barouch at Harvard Medical School—who reported that when serum from people boosted with the bivalent Omicron booster was compared to that from people boosted with a dose of the original vaccine, their levels of neutralizing antibodies against BA.4/5 were comparable. Ho’s work also showed that the bivalent booster did not produce appreciably different antibody responses against newer Omicron variants, such as BQ.1, BQ.1.1, XBB, and now XBB.1.5, which together account for 83% of new infections in the U.S. as of the first week of January. These are for antibodies, mind you...the most reactive short-term signal to a booster vaccination. There's simply no good evidence backing these new vaccines. Anyone who says otherwise doesn't know the data.
superkuh 3y ago
No. He's talking about the IgA antibodies generated in mucosal tissues with the IgM that's in both mucosal and humoral body immune compartments. In intramuscular vaccination (with whatever delivery method you want) you generate humoral IgG antibodies (to go with the IgM). IgG antibodies don't protect mucosal tissues. IgA antibodies don't protect humoral (body serum) tissues. And it's true that in the human upper respiratory mucosa epithelia igA antibodies don't stick around for very long. Levels typically drop by 4 orders of magnitude over as many months. But ANTIBODY LEVELS ARE NOT THE POINT. With intranasal booster to complement intramuscular vacination for respiratory diseases what you're doing is recruiting specialized immune cells to become resident in the upper respiratory mucosa. Both B and T cells. It's harder to test for them then for antibody binding but there are many studies showing such tissue resident virus-specialized immune cells stick around functionally for years. The point is to get these tissue resident immune cells up there and ready so they can get to work killing off infected cells and pumping out new antibodies immediately after the first few cells are infected. The faster your immune system goes into action the less damage is done. An intranasal booster complements intramuscular vaccination by getting your immune system ready in the immunological compartment infection is most likely to start in. Rolling the dice by actually getting infected to get mucosal+humoral immunity (hybrid immunity) is like crashing your car so you won't crash your car. You'll probably be fine even if it'll hurt a lot. But there's a real risk of worse. It's not a reasonable option if you can avoid it. I still haven't been infected with sars-cov-2. I'm waiting on an approved intranasal vaccine in the USA before I stop wearing N95s in public and non-home indoor spaces (and limiting my time in them). I really, really wish vaccine development for sars-cov-2 was still a priority.
- timr 3y ago
  > But ANTIBODY LEVELS ARE NOT THE POINT. With intranasal booster to complement intramuscular vacination for respiratory diseases what you're doing is recruiting specialized immune cells to become resident in the upper respiratory mucosa. Let's be clear: that's the goal, not the reality. There is no such intranasal vaccine, and your understanding of IgA/IgG/IgM/etc. is incomplete, because even though these different antibody types are associated with different tissues, it's not a categorical thing. Likewise, it's not like T- and B-cells never make it to the mucosa -- the fundamental issue is that neither form of immunity stays ramped to 11 forever, and cellular immunity takes time to spin up post-infection. To a first approximation: antibodies ramp up quickly and decline quickly, and cellular responses ramp up more slowly, and last longer. When you get infected with a respiratory pathogen, the IgA levels in your nasal mucosa spike early in part because that's the tissue the virus encounters first. If the virus lives long enough to make it elsewhere in the body, it encounters IgG/IgM and ultimately, T- and B-cells. Researchers have been chasing this idea that they can cause persistent cellular immune responses in the nasal mucosa for decades, but there's no good reason to believe it will ever happen. > I'm waiting on an approved intranasal vaccine in the USA before I stop wearing N95s in public and non-home indoor spaces (and limiting my time in them). This is not going to work. You are going to get it. If you have been vaccinated with two doses of the current vaccines and are not severely immunocompromised (e.g. currently undergoing a bone-marrow transplant), you are as well-protected as you are ever going to be. > I really, really wish vaccine development for sars-cov-2 was still a priority. I will emphasize this again: the current vaccines work. You are putting your life on hold while waiting for (effectively) a cure to the common cold. This is not remotely guaranteed to happen in your lifetime. Get two doses -- or more if you like (though there's no evidence for it) -- and be confident that you've done everything practical you can do to reduce your risk.

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
> We can maybe guess, but we don't know. There's no data. Nonsense. We have data that shows vaccine effectiveness wanes with time. We know boosters improve immunity. We've been giving out bivalent booster for over a year and we have data that they're effective. > I'm not exaggerating. [...] "science" so bad that it wouldn't pass muster at a high-school science fair. You are exaggerating. You're engaging in hyperbole that's an embarrassment to yourself. Armchair scientists should leave the medical decisions to the professionals.
- timr 3y ago
  > We have data that shows vaccine effectiveness wanes with time. No, we don't. We have confounded, poorly controlled observational studies, and extrapolation from antibody titres. > We know boosters improve immunity. No, we don't. The necessary studies have never been done. Increasing antibodies for a while (in mice) does not equal "improving immunity" in humans. > We've been giving out bivalent booster for over a year and we have data that they're effective. Well, if you say so. But actually...no. Or you'd cite it, instead of just asserting things. > Armchair scientists should leave the medical decisions to the professionals. Such as Paul Offit, FDA VRBPAC member, co-creator of the Rotavirus vaccine, and director of the vaccine education center at the Children's Hospital of Philadelphia? https://time.com/6246525/bivalent-booster-not-very-effective-paul-offit/ https://time.com/6246525/bivalent-booster-not-very-effective... https://www.nejm.org/doi/full/10.1056/NEJMp2215780 https://www.nejm.org/doi/full/10.1056/NEJMp2215780 > In his perspective piece, Offit cites data from two leading virologists—Dr. David Ho, director of the Aaron Diamond AIDS Research Center at Columbia University, and Dr. Dan Barouch at Harvard Medical School—who reported that when serum from people boosted with the bivalent Omicron booster was compared to that from people boosted with a dose of the original vaccine, their levels of neutralizing antibodies against BA.4/5 were comparable. Ho’s work also showed that the bivalent booster did not produce appreciably different antibody responses against newer Omicron variants, such as BQ.1, BQ.1.1, XBB, and now XBB.1.5, which together account for 83% of new infections in the U.S. as of the first week of January. These are for antibodies, mind you...the most reactive short-term signal to a booster vaccination. There's simply no good evidence backing these new vaccines. Anyone who says otherwise doesn't know the data.

superkuh 3y ago

No. He's talking about the IgA antibodies generated in mucosal tissues with the IgM that's in both mucosal and humoral body immune compartments. In intramuscular vaccination (with whatever delivery method you want) you generate humoral IgG antibodies (to go with the IgM). IgG antibodies don't protect mucosal tissues. IgA antibodies don't protect humoral (body serum) tissues. And it's true that in the human upper respiratory mucosa epithelia igA antibodies don't stick around for very long. Levels typically drop by 4 orders of magnitude over as many months. But ANTIBODY LEVELS ARE NOT THE POINT. With intranasal booster to complement intramuscular vacination for respiratory diseases what you're doing is recruiting specialized immune cells to become resident in the upper respiratory mucosa. Both B and T cells. It's harder to test for them then for antibody binding but there are many studies showing such tissue resident virus-specialized immune cells stick around functionally for years. The point is to get these tissue resident immune cells up there and ready so they can get to work killing off infected cells and pumping out new antibodies immediately after the first few cells are infected. The faster your immune system goes into action the less damage is done. An intranasal booster complements intramuscular vaccination by getting your immune system ready in the immunological compartment infection is most likely to start in. Rolling the dice by actually getting infected to get mucosal+humoral immunity (hybrid immunity) is like crashing your car so you won't crash your car. You'll probably be fine even if it'll hurt a lot. But there's a real risk of worse. It's not a reasonable option if you can avoid it. I still haven't been infected with sars-cov-2. I'm waiting on an approved intranasal vaccine in the USA before I stop wearing N95s in public and non-home indoor spaces (and limiting my time in them). I really, really wish vaccine development for sars-cov-2 was still a priority.

timr 3y ago
> But ANTIBODY LEVELS ARE NOT THE POINT. With intranasal booster to complement intramuscular vacination for respiratory diseases what you're doing is recruiting specialized immune cells to become resident in the upper respiratory mucosa. Let's be clear: that's the goal, not the reality. There is no such intranasal vaccine, and your understanding of IgA/IgG/IgM/etc. is incomplete, because even though these different antibody types are associated with different tissues, it's not a categorical thing. Likewise, it's not like T- and B-cells never make it to the mucosa -- the fundamental issue is that neither form of immunity stays ramped to 11 forever, and cellular immunity takes time to spin up post-infection. To a first approximation: antibodies ramp up quickly and decline quickly, and cellular responses ramp up more slowly, and last longer. When you get infected with a respiratory pathogen, the IgA levels in your nasal mucosa spike early in part because that's the tissue the virus encounters first. If the virus lives long enough to make it elsewhere in the body, it encounters IgG/IgM and ultimately, T- and B-cells. Researchers have been chasing this idea that they can cause persistent cellular immune responses in the nasal mucosa for decades, but there's no good reason to believe it will ever happen. > I'm waiting on an approved intranasal vaccine in the USA before I stop wearing N95s in public and non-home indoor spaces (and limiting my time in them). This is not going to work. You are going to get it. If you have been vaccinated with two doses of the current vaccines and are not severely immunocompromised (e.g. currently undergoing a bone-marrow transplant), you are as well-protected as you are ever going to be. > I really, really wish vaccine development for sars-cov-2 was still a priority. I will emphasize this again: the current vaccines work. You are putting your life on hold while waiting for (effectively) a cure to the common cold. This is not remotely guaranteed to happen in your lifetime. Get two doses -- or more if you like (though there's no evidence for it) -- and be confident that you've done everything practical you can do to reduce your risk.