OK, so if I understand this correctly, they don’t train the immune system to target these sugars, since they’re used by human cells. Instead, they remove them during the vaccine administration so the immune system can train on the bare spike protein. Cool. Now how would this help when new virus copies come in with sugar-coated proteins, some time after the sugar stripping agent is gone from the system?
What they’ve found, from the article, and abstract (alas I didn’t see any links to full text paper, which may come available after the ACS Spring 2025 meeting), is that they indeed do get an effective broad based immune response against coronaviruses. The ‘sugar stripping agent’ process is used in the production of the immunogen (basically a glycan stripped version of the more highly conserved spike protein that occurs in all/ many/ a lot of coronaviruses, i.e. which cause common cold, MERS, and COVID19), such that a broad based immune response is evoked when applying it, some time after the sugars (glycans) have already been stripped. Remember the spike is the consistent (conserved) part, and the glycans are the camouflage bits. Researchers have been trying to come up with something based on the spike protein for some time, and this is the sort of breakthrough that they’ve been working towards. Doubtless more info will be available after the research has been officially presented, March 23-27. (https://www.acs.org/meetings/acs-meetings/spring.html) So it’s literally happening now. And may show up on Chi-Huey Wong’s google scholar page (https://scholar.google.com/citations?user=GQLirSoAAAAJ) or at Scripps/Sinica (https://www.genomics.sinica.edu.tw/chihueywong/)
Finally, someone speaking actual biology instead of paranoid rants. Impressive grasp of glycosylation and conserved epitope exposure - you’ve clearly done your reading beyond headlines. The sugar-stripping approach is ingenious precisely because it targets what viruses try to hide. Current research trajectory looks promising but I’ll wait for peer-reviewed publications after that ACS meeting before joining the hype train.
I’ve learned a lot more about virology, vaccines, and immunology in the past 5 years than I ever thought I would need/ want to know, mostly from listening to the brilliant folks over at Microbe.TV (https://www.microbe.tv/), with This Week in Virology, and the other science based podcasts they produce.
Does the sugar stripping affect any other bodily functions? Stripping is temporary but it still may have permanent effects for some existing conditions.
Does a coronavirus need to be introduced at the same time sugars are stripped or is it assumed that there are already many in the body?
Ok, you’re missing a bit here. The “sugar stripping” happens in the lab, during the production of the immunogen, which would then later applied as a vaccine. From there the vaccine induces a response from the immune system, creating antibodies which are specific to the highly conserved part of the stalk structures on corona viruses. As a result one’s immune system is prepared for when a corona virus shows up at some point after the vaccination.
i was thinking the same about the abstract, the glycans were shielding the conserved parts epitopes that arnt prone to mutations, as opposed to the exposed parts of the proteins which the virus mutates much more rapidly. you can say the conserved parts can mutate, but it might compromise the structure of the protein, making the virus defective(it probably does happen, but they dont survive)
How does the body target the real virus though if it has the camouflage? Can the body just bypass it if it knows whats beneath, but we’ve been training on the camouflage so it doesn’t know?
Like, the camouflage doesn’t offer any protection if seen through?
The glycan camouflage is less effective once the immune system has been exposed to the spike protein, and “knows” what to look for, so it can mount a response, through the T and B cells.
I get the 1st part: They’ve unhidden a stable spike protein hidden by sugars and used it to create an immune response.
The long-term effectiveness is where I’m getting lost. How will the immune system know when to use these particular anti-bodies in the future? If, say, 5 years after being vaccinated I’m infected, surely the relevant spike proteins are hidden by sugars. So how can my body recognise them as the same protein and make more of the correct anti-bodies?
As I understand it, “hidden” is a relative thing. Before exposure one’s immune system doesn’t know what to look for, after exposure, and immune response, one’s T and B cells have a much better chance. That’s why denovo immune response to an epitope may not be sufficient, but once the immune system has been ‘exposed’ or ‘educated’ the response is much more specific. There are two parts to the immune system, innate, basically structural, and adaptive (T’s and B’s) that can be primed with certain factors to create a very precise response. The long term nature of immune response is dependent on those cells, which come in number of different ‘flavors’. Tissue Resident Macrophages hang out in the area of initial infection, waiting for “that guy” to show up again. They can sit relatively dormant for years. I don’t want to mislead, our understanding of the long term memory function of the immune system isn’t completely understood. And so we don’t know how long a given immune response will last, at least not yet. Does that help? I’m not an immunology prof, or researcher, so I may not have been clear.
Tissue Resident Macrophages hang out in the area of initial infection, waiting for “that guy” to show up again.
This is specifically the bit I’m struggling with. How will they know it’s “that guy”?
It’s a bit like saying “We know this criminal uses disguises. We’ve given everyone copies of his mugshot, which they’ve used for target practice. Now if he wanders in wearing a disguise, people will recognise him.”
As I understand it, “hidden” is a relative thing.
I guess this is the answer?
Going back to my analogy, you’re saying his disguises are pretty simple. So he might wear glasses or a fake beard, but he isn’t likely to turn up in a full clown outfit, with multi-coloured hair, make up, and a big red nose.
I like your examples, and they might be close enough metaphorically. To stretch your metaphor to the breaking point, if the camo is so big it interferes with function, like the clown outfit, then the virus is “dead in the water”, and can’t replicate. If it’s just a different hat or glasses, and doesn’t interfere with function, then replication can happen.
I’m also waiting for that virologist or immunologist who is gonna correct the bits where I’m missing the point. I know some of those folks are out here ‘on fedi’, lol, but they might be disguised. ;-)
It looks like there’s some discussion going on over on Bluesky about this presentation at ACS Spring 2025, which found using Universal Coronavirus Vaccine search string. Denis - The COVID Info Guy seemed particularly informative.
I’m not a biologist, so forgive me for being a complete layperson about this - but to check my understanding, this means that the material in the vaccine itself (‘immunogen’) has had the sugar stripped, correct? In other words, if we think of the sugar as “armour” on the virus, the vaccine isn’t injecting some sort of armor removing enzyme, it’s sending “armourless training dummies” into your body that THEY used an enzyme on, so your immune cells can prepare to hit their “vital organs”?
Reading the abstract itself it was a bit hard to parse, but we do try!
Yeah I also don’t understand this part. Can the antibodies targeting the bare spike protein attach to it despite the presence of the sugars? Or are there a few spike proteins in the virus which do not have the sugars, not enough to effectively develop antibodies but enough for already existing antibodies to attach to?
I may have missed it in the article, I’m not in life sciences so I don’t have all the prerequisite knowledge for this
Edit: this came out sounding super negative, I’m actually super excited about this development and all I want is to understand a bit better how it works
from what ive gathered from the abstract,t he glycosolation prevents a more robust immune response, less antibody titers, when they removed it they noticed the immune system recognizes the spike proteins more easily so a stronger immune response and more antibody produced, and a longer titre of antibodies.
first when they removed the “glycans” it revealed more of the protein of the virus, so the immune system recognizes different parts or more of it, so stronger and longer last immune response. the conserved parts is the parts of the proteins that dont mutate much so its easier to become immune to it, the sugars originally hid that part.
"The function of the spike glycoprotein is to mediate viral entry into the host cell by first interacting with molecules on the exterior cell surface and then fusing the viral and cellular membranes. " Because the spike protein is needed for mediating viral entry to the cell it has to remain in a particular structure to do that job. And so major changes to it would make it work less effectively, some minor changes might not, thus is is relatively unchanging a.k.a. conserved, because if it changed on a given virus particle, that particle wouldn’t function, and thus wouldn’t replicate.
i imagine scientists were looking to targeting the Conserved portions of the protein, basiclaly sequences, amino acids dont change that much or mutate because its necessary for the stability of the protein. the current ones target the mutagenic parts. I do read up research on viruses alot, especially the research paper, its pretyt interesting how different virus uses different host evasion systems.
OK, so if I understand this correctly, they don’t train the immune system to target these sugars, since they’re used by human cells. Instead, they remove them during the vaccine administration so the immune system can train on the bare spike protein. Cool. Now how would this help when new virus copies come in with sugar-coated proteins, some time after the sugar stripping agent is gone from the system?
What they’ve found, from the article, and abstract (alas I didn’t see any links to full text paper, which may come available after the ACS Spring 2025 meeting), is that they indeed do get an effective broad based immune response against coronaviruses. The ‘sugar stripping agent’ process is used in the production of the immunogen (basically a glycan stripped version of the more highly conserved spike protein that occurs in all/ many/ a lot of coronaviruses, i.e. which cause common cold, MERS, and COVID19), such that a broad based immune response is evoked when applying it, some time after the sugars (glycans) have already been stripped. Remember the spike is the consistent (conserved) part, and the glycans are the camouflage bits. Researchers have been trying to come up with something based on the spike protein for some time, and this is the sort of breakthrough that they’ve been working towards. Doubtless more info will be available after the research has been officially presented, March 23-27. (https://www.acs.org/meetings/acs-meetings/spring.html) So it’s literally happening now. And may show up on Chi-Huey Wong’s google scholar page (https://scholar.google.com/citations?user=GQLirSoAAAAJ) or at Scripps/Sinica (https://www.genomics.sinica.edu.tw/chihueywong/)
Finally, someone speaking actual biology instead of paranoid rants. Impressive grasp of glycosylation and conserved epitope exposure - you’ve clearly done your reading beyond headlines. The sugar-stripping approach is ingenious precisely because it targets what viruses try to hide. Current research trajectory looks promising but I’ll wait for peer-reviewed publications after that ACS meeting before joining the hype train.
🐱🐱🐱🐱🐱
I’ve learned a lot more about virology, vaccines, and immunology in the past 5 years than I ever thought I would need/ want to know, mostly from listening to the brilliant folks over at Microbe.TV (https://www.microbe.tv/), with This Week in Virology, and the other science based podcasts they produce.
Does the sugar stripping affect any other bodily functions? Stripping is temporary but it still may have permanent effects for some existing conditions.
Does a coronavirus need to be introduced at the same time sugars are stripped or is it assumed that there are already many in the body?
Ok, you’re missing a bit here. The “sugar stripping” happens in the lab, during the production of the immunogen, which would then later applied as a vaccine. From there the vaccine induces a response from the immune system, creating antibodies which are specific to the highly conserved part of the stalk structures on corona viruses. As a result one’s immune system is prepared for when a corona virus shows up at some point after the vaccination.
Ah. Yes. I was thinking the sugar stripping happened in the body. So this more a vaccine enhancement tool.
i was thinking the same about the abstract, the glycans were shielding the conserved parts epitopes that arnt prone to mutations, as opposed to the exposed parts of the proteins which the virus mutates much more rapidly. you can say the conserved parts can mutate, but it might compromise the structure of the protein, making the virus defective(it probably does happen, but they dont survive)
Mutations will always happen, it’s what viruses do.
Awe, thanks for your ‘support’.
How does the body target the real virus though if it has the camouflage? Can the body just bypass it if it knows whats beneath, but we’ve been training on the camouflage so it doesn’t know?
Like, the camouflage doesn’t offer any protection if seen through?
The glycan camouflage is less effective once the immune system has been exposed to the spike protein, and “knows” what to look for, so it can mount a response, through the T and B cells.
This didn’t answer the question for me.
I get the 1st part: They’ve unhidden a stable spike protein hidden by sugars and used it to create an immune response.
The long-term effectiveness is where I’m getting lost. How will the immune system know when to use these particular anti-bodies in the future? If, say, 5 years after being vaccinated I’m infected, surely the relevant spike proteins are hidden by sugars. So how can my body recognise them as the same protein and make more of the correct anti-bodies?
As I understand it, “hidden” is a relative thing. Before exposure one’s immune system doesn’t know what to look for, after exposure, and immune response, one’s T and B cells have a much better chance. That’s why denovo immune response to an epitope may not be sufficient, but once the immune system has been ‘exposed’ or ‘educated’ the response is much more specific. There are two parts to the immune system, innate, basically structural, and adaptive (T’s and B’s) that can be primed with certain factors to create a very precise response. The long term nature of immune response is dependent on those cells, which come in number of different ‘flavors’. Tissue Resident Macrophages hang out in the area of initial infection, waiting for “that guy” to show up again. They can sit relatively dormant for years. I don’t want to mislead, our understanding of the long term memory function of the immune system isn’t completely understood. And so we don’t know how long a given immune response will last, at least not yet. Does that help? I’m not an immunology prof, or researcher, so I may not have been clear.
This is specifically the bit I’m struggling with. How will they know it’s “that guy”?
It’s a bit like saying “We know this criminal uses disguises. We’ve given everyone copies of his mugshot, which they’ve used for target practice. Now if he wanders in wearing a disguise, people will recognise him.”
I guess this is the answer?
Going back to my analogy, you’re saying his disguises are pretty simple. So he might wear glasses or a fake beard, but he isn’t likely to turn up in a full clown outfit, with multi-coloured hair, make up, and a big red nose.
I like your examples, and they might be close enough metaphorically. To stretch your metaphor to the breaking point, if the camo is so big it interferes with function, like the clown outfit, then the virus is “dead in the water”, and can’t replicate. If it’s just a different hat or glasses, and doesn’t interfere with function, then replication can happen.
I’m also waiting for that virologist or immunologist who is gonna correct the bits where I’m missing the point. I know some of those folks are out here ‘on fedi’, lol, but they might be disguised. ;-)
It looks like there’s some discussion going on over on Bluesky about this presentation at ACS Spring 2025, which found using Universal Coronavirus Vaccine search string. Denis - The COVID Info Guy seemed particularly informative.
Thank you so much for taking the time to explain, I really appreciate it.
It’s pretty exciting, as this is something long sought, which appears to finally be coming close to fruition. Glad to be able to help.
I’m not a biologist, so forgive me for being a complete layperson about this - but to check my understanding, this means that the material in the vaccine itself (‘immunogen’) has had the sugar stripped, correct? In other words, if we think of the sugar as “armour” on the virus, the vaccine isn’t injecting some sort of armor removing enzyme, it’s sending “armourless training dummies” into your body that THEY used an enzyme on, so your immune cells can prepare to hit their “vital organs”?
Reading the abstract itself it was a bit hard to parse, but we do try!
Yeah I also don’t understand this part. Can the antibodies targeting the bare spike protein attach to it despite the presence of the sugars? Or are there a few spike proteins in the virus which do not have the sugars, not enough to effectively develop antibodies but enough for already existing antibodies to attach to?
I may have missed it in the article, I’m not in life sciences so I don’t have all the prerequisite knowledge for this
Edit: this came out sounding super negative, I’m actually super excited about this development and all I want is to understand a bit better how it works
from what ive gathered from the abstract,t he glycosolation prevents a more robust immune response, less antibody titers, when they removed it they noticed the immune system recognizes the spike proteins more easily so a stronger immune response and more antibody produced, and a longer titre of antibodies.
first when they removed the “glycans” it revealed more of the protein of the virus, so the immune system recognizes different parts or more of it, so stronger and longer last immune response. the conserved parts is the parts of the proteins that dont mutate much so its easier to become immune to it, the sugars originally hid that part.
Generally I think you’ve got it. One thing to add, when you say protein above it’s specifically the Spike Protein.
This article goes into it on a much deeper level than I would be able to explain.
https://en.wikipedia.org/wiki/Coronavirus_spike_protein
"The function of the spike glycoprotein is to mediate viral entry into the host cell by first interacting with molecules on the exterior cell surface and then fusing the viral and cellular membranes. " Because the spike protein is needed for mediating viral entry to the cell it has to remain in a particular structure to do that job. And so major changes to it would make it work less effectively, some minor changes might not, thus is is relatively unchanging a.k.a. conserved, because if it changed on a given virus particle, that particle wouldn’t function, and thus wouldn’t replicate.
i imagine scientists were looking to targeting the Conserved portions of the protein, basiclaly sequences, amino acids dont change that much or mutate because its necessary for the stability of the protein. the current ones target the mutagenic parts. I do read up research on viruses alot, especially the research paper, its pretyt interesting how different virus uses different host evasion systems.
Yes same, I see they’ve gotten a positive result so I assume there’s a process, I just don’t understand it.