7 ms·

Intranasal vaccine confers broad mucosal and systemic immunity against SARS-CoV2

152 points by luu 4y ago

yborg 4y ago
...in mice.
- dsjoerg 4y ago
  Great point and it's a step in the right direction.
  - rzzzt 4y ago
    It might be a sampling error on my part, but I see all the murine model breakthroughs and pretty much none of the "this was tested on humans and it did work to some extent" announcements. Phase I is fine, I'm not picky. "In mice" should be a prefix, not a suffix, eg. "Don't get your hopes up, but" or DGYHUB in short.
- hughw 4y ago
  There's a Twitter account https://twitter.com/justsaysinmice https://twitter.com/justsaysinmice who simply links to articles whose titles could use a good "IN MICE"
version_five 4y ago
All author affiliations are Chinese institutions. For Americans it's probably not coming to a pharmacy near you. I don't have a sense of the global vaccine R&D landscape but I don't belive western countries ever got any chinese covid vaccines
- davidw 4y ago
  Our mRNA vaccines were 'better' from what I understand.
  - htss2013 4y ago
    If mRNA is better, then why didn't the Chinese ever use it or produce a version of it? Maybe you could argue they were slow to get on the mRNA train at first, but years into the pandemic there is no plausible reason for them to not use the best technology. They are fully capable of producing mRNA vaccines just as well as the West. IP rights have never been an issue for China. The claim that it's stubborn pride is also weak because they could simply tweak a few meaningless details and claim it's superior to the West's version.
    - anonymouskimmer 4y ago
      mRNA vaccines are still novel enough that proprietary information matters with respect to turnaround time. Why did a huge company like Pfizer team up with a small one like BioNTech? China does have at least a couple of mRNA vaccines (Walvax COVID-19 vaccine and CanSino Biologics Inc COVID-19 mRNA Vaccine), but it took them until 2021/2022 to get them to trials. They just didn't seem to have the experience in making and testing mRNA vaccines that Western companies did.
    - tw1984 4y ago
      > If mRNA is better, then why didn't the Chinese ever use it or produce a version of it? You made two mistakes in one sentence. First of all, Chinese companies have multiple mRNA vaccines in development and at least one of them has been approved. I can get it today in my neighbourhood clinic if I want. See link below. https://www.bbc.com/news/world-asia-china-65036474 https://www.bbc.com/news/world-asia-china-65036474 Secondly, when there is something that is not produced or produced in China, it doesn't mean it is useless or fancy. China doesn't make 3nm chips not because it is not cool, it is because the advanced tech is simply not available in China. China does make high end LCD panels which the US doesn't build on its own, it is not because the tech is fancy and the US couldn't do it, it is simply because the industry is not considered economically viable in the US but a good money making business in China.
- maw 4y ago
  I don't know about other countries but in Mexico they gave out Cansino and Sinovac among many others. I count myself fortunate to live in an area where they were administering A-Z.
  - HillRat 4y ago
    Yeah, Sinovac was useless; everyone I know in Mexico who got it came down repeatedly with COVID after vaccination, only improving after they were able to get AZ or the mRNA vaccines in the US. Hopefully this signals better vaccines on the horizon for China, given what they went through once lockdown collapsed there.
    - osigurdson 4y ago
      >> Hopefully this signals better vaccines on the horizon for China Better vaccines everywhere would be good. mRNA vaccines were laughably crappy - essentially just a temporary prophylactic.
    - VagueMag 4y ago
      > everyone I know in Mexico who got it came down repeatedly with COVID after vaccination This is a pretty common story with the mRNA and DNA/AAV vaccines as well. Did any of them wind up in the hospital?
    - jbm 4y ago
      Just to mirror what the other comment said, the MRNA vaccines were not so great at warding off symptomatic Covid; I'm curious how hospitalizations went w/ people who used Sinovac and the other Chinese vaccines. I mean, if they really were completely worthless, I'd have expected China to have been much worse off after their lockdowns ended.
    - fuckyah 4y ago
      [dead]
- celdon25 4y ago
  How often do you actually see news of "research breakthroughs" panning out as far as things you can actually buy later on? Chinese or not.
medvezhenok 4y ago
RadVac in the Boston area had an intranasal vaccine out by June of 2020. Not FDA approved/authorized, but quite a few people took it early on with little adverse consequences. About 6 months earlier than the first FDA authorized vaccines became available. https://radvac.org/vaccine/ https://radvac.org/vaccine/
- fsh 4y ago
  There is no reason to believe that this actually worked. There were lots of vaccine candidates in early 2020, and many of them failed to produce a strong enough immune responce. This even happened to big corporations like Sanofi-GSK. The hard part is not to produce some vaccine candidates, but to test the safety and efficacy.
- ethanbond 4y ago
  [flagged]
- zamnos 4y ago
  If we're playing who was first, BioNTech's mRNA vaccine was ready in the lab in January, right after COVID-19 was sequenced, and went into trials in April/May 2020. It's just they had to prove safety and efficacy (which to be clear, are paramount for a new medicine), along with scaling up production, before worldwide distribution. https://impfung.biontech.de/en/impfung/project-lightspeed.html https://impfung.biontech.de/en/impfung/project-lightspeed.ht...
TheRealPomax 4y ago
This should really have "in mice" added at the end of the title, even if the publication itself omits this because it's in the abstract. As published, this has effectively nothing to do with what people think it has anything to do with yet.
- actuallyalys 4y ago
  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 4y 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 4y 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?
BigCryo 4y ago
Time it's for real
DoreenMichele 4y ago
Intranasal, but not intramuscular vaccination, elicited spike-specific respiratory mucosal IgA and residential T cell immune responses, in addition to systemic neutralizing antibodies and T cell immune responses against most Omicron subvariants. SARS-CoV-2 infection starts in the upper respiratory system, where the nasopharyngeal tract is at the forefront. To prevent viruses from attaching and replicating at the mucosal epithelium, effective mucosal immunity in the airway is critically important. Although only in mice, it does at least have a solid hypothesis for why they wish to do it this way.
- jxramos 4y ago
  I heard this criticism recently that injection site has little relation to the natural point of infection and if you overlap the two there could be some stronger synergies elicited by the location somehow. Also you don't risk the accidental intravenous delivery which can have terrible outcomes when the syringe isn't first aspirated to sample if you hit some open vasculature along the way.
  - DoreenMichele 4y ago
    The entire reason the lungs are lined with mucus is to keep out invaders. So there's that.
    - jxramos 4y ago
      yah that's the rub, to expose to a natural infection site while also overcoming the defenses of that site but not so much that things spin out of control. Tricky gambit. But intranasal is like the pharynx and nasal passages and turbinates stuff, not all the way down in the lungs.
      - DoreenMichele 4y ago
        Those are all interconnected.
        4y ago
EamonnMR 4y ago
Intranasal is only viable for people who are truly terrified of needles. Instead of a swollen arm you get the head cold experience. Never again; I hate getting pricked as much as the next guy but I really like being able to breathe through my nose.
- ceejayoz 4y ago
  Intranasal vaccination is believed to be potentially more effective because the nasal mucosa are where it enters the body. From the link: > Some studies on respiratory viruses such as respiratory syncytial virus (RSV) and influenza virus provide substantial evidence that mucosal immunity is key to the effective control of respiratory viruses. > However, almost all COVID-19 vaccines approved for human usage, including inactivated virus, lipid nanoparticle-encapsulated mRNA, protein subunit of spike or RBD, and adenovirus vectored vaccines, are administered via intramuscular injection. These vaccines can induce a systemic immune response that protects against severe disease and mortality but not a mucosal immune response and are insufficient in preventing upper respiratory infection and transmission, especially with the emergence of highly transmissible Omicron subvariants.
  - smegsicle 4y ago
    tl;dr: different lymph nodes are activated by an injected vaccine than those which would be involved in first-line-defense against a real respiratory virus
Guthur 4y ago
[flagged]
aaron695 4y ago
[dead]
realworldperson 4y ago
[dead]
perlgeek 4y ago
There have been several attempts at developing intranasal COVID-19 vaccines, all of them have had disappointing results so far (mostly that the immunity waned pretty quickly, if I remember correctly). It would be far more convincing if the authors explicitly acknowledged that in the abstract, and gave a good reason why they think their approach is more promising.

152 points by luu 4y ago

yborg 4y ago

...in mice.

dsjoerg 4y ago
Great point and it's a step in the right direction.
- rzzzt 4y ago
  It might be a sampling error on my part, but I see all the murine model breakthroughs and pretty much none of the "this was tested on humans and it did work to some extent" announcements. Phase I is fine, I'm not picky. "In mice" should be a prefix, not a suffix, eg. "Don't get your hopes up, but" or DGYHUB in short.
hughw 4y ago
There's a Twitter account https://twitter.com/justsaysinmice https://twitter.com/justsaysinmice who simply links to articles whose titles could use a good "IN MICE"

version_five 4y ago

All author affiliations are Chinese institutions. For Americans it's probably not coming to a pharmacy near you. I don't have a sense of the global vaccine R&D landscape but I don't belive western countries ever got any chinese covid vaccines

davidw 4y ago
Our mRNA vaccines were 'better' from what I understand.
- htss2013 4y ago
  If mRNA is better, then why didn't the Chinese ever use it or produce a version of it? Maybe you could argue they were slow to get on the mRNA train at first, but years into the pandemic there is no plausible reason for them to not use the best technology. They are fully capable of producing mRNA vaccines just as well as the West. IP rights have never been an issue for China. The claim that it's stubborn pride is also weak because they could simply tweak a few meaningless details and claim it's superior to the West's version.
  - anonymouskimmer 4y ago
    mRNA vaccines are still novel enough that proprietary information matters with respect to turnaround time. Why did a huge company like Pfizer team up with a small one like BioNTech? China does have at least a couple of mRNA vaccines (Walvax COVID-19 vaccine and CanSino Biologics Inc COVID-19 mRNA Vaccine), but it took them until 2021/2022 to get them to trials. They just didn't seem to have the experience in making and testing mRNA vaccines that Western companies did.
  - tw1984 4y ago
    > If mRNA is better, then why didn't the Chinese ever use it or produce a version of it? You made two mistakes in one sentence. First of all, Chinese companies have multiple mRNA vaccines in development and at least one of them has been approved. I can get it today in my neighbourhood clinic if I want. See link below. https://www.bbc.com/news/world-asia-china-65036474 https://www.bbc.com/news/world-asia-china-65036474 Secondly, when there is something that is not produced or produced in China, it doesn't mean it is useless or fancy. China doesn't make 3nm chips not because it is not cool, it is because the advanced tech is simply not available in China. China does make high end LCD panels which the US doesn't build on its own, it is not because the tech is fancy and the US couldn't do it, it is simply because the industry is not considered economically viable in the US but a good money making business in China.
maw 4y ago
I don't know about other countries but in Mexico they gave out Cansino and Sinovac among many others. I count myself fortunate to live in an area where they were administering A-Z.
- HillRat 4y ago
  Yeah, Sinovac was useless; everyone I know in Mexico who got it came down repeatedly with COVID after vaccination, only improving after they were able to get AZ or the mRNA vaccines in the US. Hopefully this signals better vaccines on the horizon for China, given what they went through once lockdown collapsed there.
  - osigurdson 4y ago
    >> Hopefully this signals better vaccines on the horizon for China Better vaccines everywhere would be good. mRNA vaccines were laughably crappy - essentially just a temporary prophylactic.
  - VagueMag 4y ago
    > everyone I know in Mexico who got it came down repeatedly with COVID after vaccination This is a pretty common story with the mRNA and DNA/AAV vaccines as well. Did any of them wind up in the hospital?
  - jbm 4y ago
    Just to mirror what the other comment said, the MRNA vaccines were not so great at warding off symptomatic Covid; I'm curious how hospitalizations went w/ people who used Sinovac and the other Chinese vaccines. I mean, if they really were completely worthless, I'd have expected China to have been much worse off after their lockdowns ended.
  - fuckyah 4y ago
    [dead]
celdon25 4y ago
How often do you actually see news of "research breakthroughs" panning out as far as things you can actually buy later on? Chinese or not.

medvezhenok 4y ago

RadVac in the Boston area had an intranasal vaccine out by June of 2020. Not FDA approved/authorized, but quite a few people took it early on with little adverse consequences. About 6 months earlier than the first FDA authorized vaccines became available. https://radvac.org/vaccine/ https://radvac.org/vaccine/

fsh 4y ago
There is no reason to believe that this actually worked. There were lots of vaccine candidates in early 2020, and many of them failed to produce a strong enough immune responce. This even happened to big corporations like Sanofi-GSK. The hard part is not to produce some vaccine candidates, but to test the safety and efficacy.
ethanbond 4y ago
[flagged]
zamnos 4y ago
If we're playing who was first, BioNTech's mRNA vaccine was ready in the lab in January, right after COVID-19 was sequenced, and went into trials in April/May 2020. It's just they had to prove safety and efficacy (which to be clear, are paramount for a new medicine), along with scaling up production, before worldwide distribution. https://impfung.biontech.de/en/impfung/project-lightspeed.html https://impfung.biontech.de/en/impfung/project-lightspeed.ht...

TheRealPomax 4y ago

This should really have "in mice" added at the end of the title, even if the publication itself omits this because it's in the abstract. As published, this has effectively nothing to do with what people think it has anything to do with yet.

actuallyalys 4y ago
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 4y 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 4y 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?

BigCryo 4y ago

Time it's for real

DoreenMichele 4y ago

Intranasal, but not intramuscular vaccination, elicited spike-specific respiratory mucosal IgA and residential T cell immune responses, in addition to systemic neutralizing antibodies and T cell immune responses against most Omicron subvariants. SARS-CoV-2 infection starts in the upper respiratory system, where the nasopharyngeal tract is at the forefront. To prevent viruses from attaching and replicating at the mucosal epithelium, effective mucosal immunity in the airway is critically important. Although only in mice, it does at least have a solid hypothesis for why they wish to do it this way.

jxramos 4y ago
I heard this criticism recently that injection site has little relation to the natural point of infection and if you overlap the two there could be some stronger synergies elicited by the location somehow. Also you don't risk the accidental intravenous delivery which can have terrible outcomes when the syringe isn't first aspirated to sample if you hit some open vasculature along the way.
- DoreenMichele 4y ago
  The entire reason the lungs are lined with mucus is to keep out invaders. So there's that.
  - jxramos 4y ago
    yah that's the rub, to expose to a natural infection site while also overcoming the defenses of that site but not so much that things spin out of control. Tricky gambit. But intranasal is like the pharynx and nasal passages and turbinates stuff, not all the way down in the lungs.
    - DoreenMichele 4y ago
      Those are all interconnected.
      - 4y ago

EamonnMR 4y ago

Intranasal is only viable for people who are truly terrified of needles. Instead of a swollen arm you get the head cold experience. Never again; I hate getting pricked as much as the next guy but I really like being able to breathe through my nose.

ceejayoz 4y ago
Intranasal vaccination is believed to be potentially more effective because the nasal mucosa are where it enters the body. From the link: > Some studies on respiratory viruses such as respiratory syncytial virus (RSV) and influenza virus provide substantial evidence that mucosal immunity is key to the effective control of respiratory viruses. > However, almost all COVID-19 vaccines approved for human usage, including inactivated virus, lipid nanoparticle-encapsulated mRNA, protein subunit of spike or RBD, and adenovirus vectored vaccines, are administered via intramuscular injection. These vaccines can induce a systemic immune response that protects against severe disease and mortality but not a mucosal immune response and are insufficient in preventing upper respiratory infection and transmission, especially with the emergence of highly transmissible Omicron subvariants.
- smegsicle 4y ago
  tl;dr: different lymph nodes are activated by an injected vaccine than those which would be involved in first-line-defense against a real respiratory virus

Guthur 4y ago

[flagged]

aaron695 4y ago

[dead]

realworldperson 4y ago

[dead]

perlgeek 4y ago

There have been several attempts at developing intranasal COVID-19 vaccines, all of them have had disappointing results so far (mostly that the immunity waned pretty quickly, if I remember correctly). It would be far more convincing if the authors explicitly acknowledged that in the abstract, and gave a good reason why they think their approach is more promising.